Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate ...airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters.
This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method.
There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53-5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6-1510) ng/ml compared to controls, median (IQR) of 1675 (536.8-2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005).
Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.
Background COVID-19 leads to severe overwhelming inflammation in some patients mediated by various cytokines (cytokine storm) that usually leads to severe illness accompanied by cardiovascular ...manifestations. Growth differentiation factor-15 is a cytokine induced by stress and is associated with inflammatory processes in the lung and heart. This study aimed to measure the level of serum growth differentiation factor (GDF-15) in children with COVID-19 and to correlate it with the disease severity, cardiac affection, and the outcome of COVID-19. Methods A cross-sectional study was conducted on 144 children; 72 children diagnosed with COVID-19, and 72 healthy children. The severity of COVID-19 was assessed clinically, laboratory, and radiologically. Echocardiography was done within 48 h of admission for COVID-19 patients. Serum GDF-15 was measured by ELISA for both patients and controls. Results Serum GDF-15 level was significantly higher in patients with COVID-19 than in controls (p < 0.01). In COVID-19 patients with severe clinical grading, those who were hospitalized in the PICU, and those who died, serum GDF-15 levels were greater. individuals with cardiac manifestations exhibited significantly higher serum GDF-15 levels than individuals without them. In children with COVID-19, increased GDF-15 was correlated to poorer ejection fraction and higher INR using multivariate linear regression analysis. Conclusion Serum GDF-15 is a promising biomarker of COVID-19, it can be used as a predictor of cardiac manifestations in children with COVID-19 and severe disease. Keywords: COVID-19, Heart, GDF-15, Biomarkers, Child
Chronic kidney disease (CKD) is a worldwide public health problem due to its increasing prevalence worldwide. Endoplasmic reticulum (ER) stress has been shown to play a role in the pathogenesis of ...various renal diseases in humans. It leads to the activation of the unfolded protein response (UPR) which triggers three known trans membrane sensors in the ER: activating transcription factor 6 (ATF6), inositol-requiring enzyme I (IRE1), and PKR (double-stranded RNA-dependent protein kinase)-like ER protein kinase (PERK). The activation of these signal transduction pathways can result in cell death, inflammation, and fibrosis in the context of CKD.
The aim of this study was to detect the level of gene expression of activating transcription factor 6 (ATF6), inositol-requiring enzyme I (IRE1), and PKR (double-stranded RNA-dependent protein kinase)-like ER protein kinase (PERK) in chronic kidney disease patients.
This study was carried out on eighty subjects, 50 patients with CKD (25 with hypertension and 25 without hypertension) and 30 healthy subjects served as controls. All studied subjects underwent laboratory investigations, including CBC, Serum Lipid profile: Total cholesterol, Triglycerides, HDL-cholesterol and LDL-cholesterol, liver and kidney functions, fasting and 2 h postprandial blood glucose and HbA1C, serum level of IL6 and gene expression of ATF6, IRE1 and PERK using real time PCR technique.
There was a significant increase in relative quantitation (RQ) of gene expression of IRE1, ATF6 and PERK in chronic kidney patient groups with hypertension and without hypertension compared to control group. Also, there was a significant positive correlation of PERK and ATF6 gene expressions and a significant negative correlation of PERK gene expressions and GFR in groups I&II.
Endoplasmic reticulum (ER) stress occurs in CKD with activation of gene expression of three trans-membrane sensors in the ER: activating transcription factor 6 (ATF6), inositol-requiring enzyme I (IRE1), and PKR (double-stranded RNA-dependent protein kinase)-like ER protein kinase (PERK).
•Endoplasmic reticulum (ER) stress occurs in CKD.•A significant increase in gene expression of PERK, ATF6 and IRE1 was detected in chronic kidney patients.•Patients with CKD have a higher prevalence of dyslipidemias.•Serum pro-inflammatory cytokines (IL-6) may be predictive of the development of.•CKD patients should be considered as patients at very high risk for CVD.
Background
All pediatric health organizations are concerned about the impact of coronavirus disease on children, especially on those with other comorbidities; fortunately, pediatric cases appear to ...be less severe than in adults (De Luca et al. in Pediatr Respir Rev 5:9–14, 2020). The purpose of this study is to characterize chest CT findings of children with and without comorbidities who had confirmed coronavirus disease (COVID-19) and to investigate the relation between chest CT findings and the clinical severity of COVID-19 pneumonia and their laboratory findings.
Results
The study was conducted on 36 patients, 72.2% of whom had associated comorbidities. Twenty-three patients (63.88%) had abnormal CT findings. Consolidative patches were the most common radiological sign (55.6%) followed by ground glass opacities (50%). The lesions were bilateral (58.3%), having predominantly peripheral distribution (38.9%) with predominant left lower lobe affection (25%). Cases with clinically severe chest conditions had significantly more prevalent consolidative patches (
p
= 0.026) which show a higher CT density (
p
= 0.01) and a significantly higher CT severity score (SS) compared to other groups (
p
= 0.029). The cutoff of severity score 4/20 had 100% sensitivity and 78.12% specificity in the diagnosis of severe cases. There were no statistically significant differences between patients with or without comorbidities regarding CT-SS or any radiological signs.
Conclusions
Consolidation was the most common radiological finding in children with COVID-19 and was more prevalent and denser in severe cases. The CT-SS may be used as a complementary tool for the evaluation of the severity of the chest condition. Chest CT-SS more than 4 can be used as an indicator of severe cases, yet no significant difference in CT-SS between patients with associated comorbidities or not.
Background
We recently adopted a guideline for chronic cough in children in the Egyptian health system. Adapting clinical practice guidelines (CPGs) to the local healthcare setting is a valid ...alternative to de-novo development that can improve their uptake and implementation without demanding a substantial drain on resources. The objective of this study was to adapt evidence-based recommendations from global high-quality CPGs for children with a chronic cough to suit the Egyptian healthcare context.
Methods
We followed the Adapted ADAPTE methodological framework for guideline adaptation. This process includes three phases: set-up, adaptation, and finalization. A guideline adaptation group (GAG) and an external review group including clinical content experts and methodologists conducted the process.
Results
The GAG adapted 10 sections of recommendations from three original CPG(s) including (i) the American College of Chest Physicians (ACCP) 2006–2020, (ii) the European Respiratory Society (ERS) 2019, (iii) the Korean Academy of Asthma, Allergy and Clinical Immunology (KAAACI) 2018. A set of CPG implementation tools was added to enhance implementability including an algorithm, a slide presentation for clinical diagnosis, investigations and treatment of chronic cough, patient education, and online resources.
Conclusion
The adapted CPG provides pediatricians and related healthcare workers with applicable evidence-based recommendations for chronic cough in children in Egypt. The project also highlighted the utility of Adapted ADAPTE and the invaluable collaboration between the clinical and methodological experts for the adaptation of pediatric national guidelines.
Background
We recently adapted a guideline for Community-Acquired Pneumonia (CAP) in children to the Egyptian health system. Adaptation of evidence-based clinical practice guidelines to the local ...healthcare context is a valid alternative to de novo development that can upgrade their application without enforcing a major burden on resources. The objective of this manuscript is to elucidate diagnosis, treatment, and prevention of CAP as well as methods used for the adaptation process to produce the 1st National Guideline for Community-Acquired Pneumonia in children in Egypt using Adapted ADAPTE method. The full process was described extensively with all three phases of set up, adaptation, and finalization. An adaptation group and an external review including clinical content experts and methodologists conducted the process.
Results
The authors adapted 10 principal categories of recommendations from three source Clinical Practice Guidelines. Recommendations incorporate; common clinical manifestations, indications for hospitalization and intensive care unit admission, indications for laboratory investigations and radiology in diagnosis, choice of empiric antibiotic therapy in the outpatient and hospitalized children with non-complicated CAP and the duration of therapy, the role of influenza antiviral therapy, follow-up anticipated response to therapy, management of non-responding pneumonia, criteria of safe discharge, and prevention of CAP. Many tools were gathered and established to improve implement ability containing two clinical algorithms for management of non-complicated CAP and for non-responding pneumonia in children, pathway for assessment of severity of CAP in primary care facilities, medication tables, simplified Arabic patient information, PowerPoint slide presentation lecture for management of CAP, and online resources.
Conclusion
The final clinical guideline supports pediatricians and related healthcare workers with evidence-based applicable guidance for managing community-acquired pneumonia in Egypt. This work demonstrated the efficiency of Adapted ADAPTE and highlighted the importance of a cooperative clinical and methodological professional group for adaptation of national guidelines.
Avascular necrosis (AVN) is a debilitating condition characterized by bone tissue death due to inadequate blood supply, leading to joint dysfunction and collapse. This study investigates the ...potential association between AVN and COVID-19, focusing on genetic factors such as NOS3 polymorphisms. A total of 180 individuals were included, comprising 120 COVID-19 patients and 60 healthy controls. Clinical, haematological, biochemical, and genetic parameters were assessed. Results revealed significant differences in respiratory and heart rates, haematological counts, and biochemical markers between AVN and control groups. Genetic analysis showed a higher prevalence of the TG genotype and G allele in NOS3 rs1799983 polymorphism among AVN patients. Additionally, NOS3 rs2070744 polymorphism correlated with various clinical parameters, including blood pressure, heart rate, and haematological indices. This study highlights the potential role of genetic factors in predisposing individuals to AVN following COVID-19 infection.
Abstract Background Coronavirus disease 2019 (COVID-19) is a newly discovered RNA betacoronavirus infection. It has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ...Angiotensin II (Ang-II) is a mitochondrial toxin that under normal circumstances is rapidly removed by angiotensin converting enzyme 2 (ACE-2). SARS-CoV-2 uses the receptor ACE-2 for host cell entry and viral replication. ACE-2 proteins are occupied and downregulated by SARS-CoV-2. ACE-2 downregulation has been directly linked to toxic over accumulation of Ang-II. Accumulating Ang-II triggers many severe and fatal conditions such as acute respiratory distress syndrome (ARDS). Aim of the Work To assess the serum level of Ang-II and correlate it with the severity of COVID-19 infection in pediatric patients. Patients and Methods This case control study was conducted on 45 positive COVID-19 RT-PCR children who were compared to age and sex matched 45 healthy controls. Clinical examination, laboratory assays and imaging studies were done for the patients group to assess the severity of COVID–19 infection. Serum Ang-II was measured by ELISA for both groups and correlated with clinical (heart rate, blood pressure, respiratory rate and oxygen saturation), laboratory (total leucocytic count, lymphocytes, neutrophils, serum ferritin, ESR and CRP) and radiological (chest x-ray and CORAD score of CT chest ) parameters of the patients. Results The median “IQR” of serum Ang-II was significantly higher in the COVID-19 patients than in the controls (100 (88-137) ng/L) versus 20 (15-25) ng/L) (p-value= 0.001). There were statistically significant positive correlations between serum Ang-II levels and different grades of clinical severity classification (rs = 0.92, p-value=0.001) and CORAD score of CT chest. On the other hand, no statistically significant correlations were found between serum levels of Ang-II and total leucocytic count, lymphocytes, neutrophils, ESR and CRP. Conclusion Serum Ang-II could be used as a biomarker in predicting the severity of COVID-19 infection in pediatrics.
Abstract Background Cystic fibrosis (CF) is an exhausting and time-consuming disease that can interfere or impair typical daily life activities and social interactions. Aim and Objectives Evaluation ...of psychological aspects and Quality of life in cystic fibrosis patients. Subjects and Methods This was a cross sectional study, conducted at the Paediatric Chest Clinic, Children's Hospital, Ain Shams University on 31 patients with verified diagnosis of CF compared to 31 healthy children. Psychological assessment was done using Children depression Inventory (CDI) Scale, Spence Children’s Anxiety Scale, and The Pediatric Quality of Life (PedsQLTM) Scales. Result: CF patients experienced statistically significant higher levels of depression and anxiety than their healthy peers (p < 0.001; p = 0.001, respectively). There were no significant differences in PedsQLTM Scales between the CF patients and the healthy controls (p > 0.05). Conclusion This study is significantly important for revealing that psychiatric symptoms are prevalent among children with CF, which implies that annual symptom screening is justified.
Systemic lupus erythematosus (SLE) is a common autoimmune disease marked by the formation of apoptotic debris and the presence of autoantibodies that target nuclear components. At this moment, the ...actual cause of SLE is uncertain. Genetic variables have been well proven to have a significant role in the propensity of SLE. This study aimed to investigate the effect of (ZNF76) rs (10947540) and (SCUBE) rs (1888822) gene polymorphism in patients with systemic lupus erythematosus. A case control study has been carried out at Medical Biochemistry & Molecular biology and Rheumatology unit of Internal Medicine Departments, Faculty of Medicine, Menoufia University, Egypt, for 1-year duration between 1 June 2022 and 1 June 2023. Sixty patients were females (75%) and twenty patients were males (25%). Their ages ranged from 19 to 53 years. Their disease durations ranged from 7 months to 20 years. The findings indicated that the TC genotype of the ZNF76 rs10947540 gene increases the risk of SLE by 2.274-fold, while the dominant TC + CC increases the risk by 2.472-fold, and the C allele increases the risk by 2.115-fold. Additionally, the results showed that the TT genotype of the SCUBE3 rs1888822 gene increases the risk of SLE by 3.702-fold, the dominant GT + TT increases the risk by 2.304-fold, and the T allele increases the risk by 2.089-fold, while the GT genotype increases the risk by 1.918-fold. The study revealed significant associations between the genotypes of these polymorphisms and certain clinical parameters in SLE patients. These findings highlight the potential genetic contributions to SLE susceptibility and its clinical manifestations, providing valuable insights for future research and potential personalized approaches to the management of this complex autoimmune disease.
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