Association between arachidonate lipoxygenase 15,c.-292 C > T gene polymorphism and non-cystic fibrosis bronchiectasis in children: a pilot study on the effects on airway lipoxin A4 and disease phenotype.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Serum growth differentiation factor-15 (GDF-15) is a biomarker of cardiac manifestations in children with COVID-19.

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.

Clinical Significance of MiR-130b and MiR-125b as Biomarkers in Hepatocellular Carcinoma.

OBJECTIVE: This study aimed to assess the role of miR-130b and miR-125b expression in Hepatocellular Carcinoma (HCC) progression. SUBJECTS AND METHODS: This study was carried out on 150 subjects classified into three groups: Group I, 50 healthy controls; Group II, 50 patients with liver cirrhosis; Group III, 50 patients with HCV related HCC. The controls were frequency matched based on age and sex with the other groups. All individuals were subjected to testing for liver function, alpha-fetoprotein (AFP), and viral markers. miR-130b and miR-125b were detected in plasma using a quantitative real-time RT-PCR. RESULTS: miR-130b was significantly upregulated, whereas miR-125b was significantly downregulated in HCC patients compared with cirrhotic patients and healthy controls. There was a significant correlation between miR-130b and AFP and tumor size. Receiver operating curve (ROC) analyses suggested that plasma miR-130b had a significant diagnostic value for HCC with a sensitivity of 92% and a specificity of 77.5%.  A sensitivity of 85.5% and a specificity of 82.5% was observed for  miR-125b for HCC. CONCLUSION: Plasma miR-130b and miR-125b may play a role in disease progression and development of HCC and may act as potential biomarkers for the diagnosis of HCC.

Sputum neutrophil elastase and its relation to pediatric bronchiectasis severity: A cross-sectional study.

Background and Aims: Sputum neutrophil elastase (NE) is a marker of neutrophilic airway inflammation in bronchiectasis. Yet, not much is known about its role in pediatric bronchiectasis severity. This study aimed to assess the sputum NE value as a biomarker of clinical and radiological severity in pediatric bronchiectasis. Methods: This was a cross-sectional study assessing sputum NE in a total of 50 bronchiectasis patients under the age of 18 years-30 patients with cystic fibrosis (CF) and 20 patients with non-CF bronchiectasis were included. Bronchiectasis severity was assessed using Shwachman-Kulczycki (SK) score, CF-ABLE score, and CF risk of disease progression score, among CF patients, and bronchiectasis severity index (BSI) and FACED criteria among non-CF bronchiectasis patients, associations between sputum NE and bronchiectasis severity were assessed in both patient groups. Results: Sputum NE was directly correlated with C-reactive protein (r = 0.914, p < 0.001), (r = 0.786, p < 0.001), frequency of exacerbations (r = 0.852, p < 0.001) (r = 0.858, p < 0.001), exacerbations severity (r = 0.735, p = 0.002), (r = 0.907, p < 0.001), and the number of hospital admissions (r = 0.813, p < 0.001), (r = 0.612, p =0.004) in the last year among CF, and non-CF bronchiectasis patients, respectively. Additional linear correlations were found between sputum NE, CF risk of disease progression score (p < 0.001), CF-ABLE score (p < 0.001), and lower forced expiratory volume 1% of predicted (p = 0.017; ρ = -0.8) among CF patients. Moreover, sputum NE was positively correlated with the neutrophil count (p = 0.018), and BSI severity score (p = 0.039; ρ = 0.465) among non-CF bronchiectasis patients. Conclusions: Sputum NE may be considered a good biomarker of bronchiectasis severity in both CF and non-CF bronchiectasis patients, as confirmed by the exacerbations rate, CF risk of disease progression, and BSI scores.

Clinical Characteristics and Pulmonary Computerized Imaging Findings of Critically Ill Egyptian Patients with Multisystem Inflammatory Syndrome in Children.

Objectives. This study was carried out to delineate the patients' characteristics and the imaging findings and their relation to some biochemical markers of 31 critically ill patients with MIS-C. Design. A retrospective cross-sectional study including all critically ill MIS-C patients admitted to the PICU from June 23rd to July 22nd, 2020. Results. Eighteen males and 13 females, with a median age of 9 years (interquartile range 6-11) presented mainly with fever (100%) and hypotension (100%). Abnormalities in the chest computed tomography were detected in 22 cases (71%). Consolidation and architecture distortion were detected in 58.1% of patients; bilateral lesions and lower lobe infiltrates, each, was evident in 64.5% of patients, while the peripheral distribution of lesions was seen in 71% of the cases. Pleural thickening and effusion, each, was found in 51.6% of the patients. In this small case series, the presence of high ferritin was significantly associated with the bilaterality of the lesions. Elevated C-reactive protein was associated with the peripheral distribution of the lesions. Thrombocytopenia and hypoalbuminemia were significantly correlated with the CT disease stage and CT severity score respectively. Conclusions. Although a few children in this group of MIS-C patients presented with respiratory manifestations, yet, most of them demonstrated significant radiological lung involvement, which necessitates a longer-term follow-up.

Serum homocysteine level in pediatric patients with COVID-19 and its correlation with the disease severity.

BACKGROUND: Thrombosis and embolism are possible complications in coronavirus disease 2019 (COVID)-19-positive pediatric patients. Although the risk is lesser in children than it is in adults, it does exist during acute infection and multi-inflammatory syndrome in children. Biomarkers such asd-dimer, prothrombin time, and fibrinogen degradation products are ineffective at detecting disease severity. Homocysteine (Hcy) is a prothrombotic factor that has been reported to be higher in adult COVID-19 patients, leading to speculation that it could be used as a biomarker for disease severity. PURPOSE: To detect the correlation between serum total homocysteine (tHcy) level and the severity of COVID-19 in pediatrics. METHODS: A cross-sectional study was conducted on 40 children with COVID-19 and 40 healthy control subjects. Serum tHcy was measured by enzyme-linked immunosorbent assay and correlated with the clinical, laboratory, and radiological parameters of the patients. RESULTS: The median serum tHcy level in COVID-19 patients was 27.5 (interquartile range [IQR]: 23-31.75) µmol/L, while that in the controls was 1.8 (IQR: 1.6-1.875) µmol/L. There was a statistically significant increase in the tHcy level in cases compared to controls (p < 0.001). There was a statistically significant positive correlation between serum tHcy and d-dimer, ferritin, alanine transaminase, aspartate transaminase, blood urea nitrogen, and a highly significant positive correlation between tHcy and COVID-19 reporting and data system score, pediatric intensive care unit admission, and the disease severity classification. CONCLUSION: Hcy could be a biomarker of importance in predicting the severity of COVID-19 in pediatrics.

COVID-19-Related Multisystem Inflammatory Syndrome in Children Presenting With New-Onset Type 1 Diabetes in Severe Ketoacidosis: A Case Series.

OBJECTIVE: To report and describe cases of children presenting with coronavirus disease 2019 (COVID-19)-related multisystem inflammatory syndrome in children (MIS-C) with new-onset type 1 diabetes mellitus (T1DM) in severe diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS: This prospective observational study was conducted to characterize children with COVID-19-related MIS-C and new-onset T1DM who were in DKA. MIS-C was diagnosed if Centers for Disease Control and Prevention and World Health Organization criteria were fulfilled. RESULTS: Six cases were identified. The patients were critically ill and in nonfluid responsive shock (combined hypovolemic and cardiogenic or distributive shock). All had cardiac involvement. One patient had a Kawasaki shock-like presentation. All needed aggressive treatment with careful monitoring of fluid balance (because of associated cardiac dysfunction), early institution of vasoactive/inotropic supports, and use of methylprednisolone and intravenous immunoglobulins. The latter are better administered after DKA resolution to avoid undue volume overload and fluid shifts while the patients are in DKA. CONCLUSIONS: Awareness of MIS-C coexistence with DKA at T1DM onset is crucial for rapid proper management.

Treatment of MIS-C in Children and Adolescents.

Purpose of Review: Different treatment approaches have been described for the management of COVID-19-related multisystem inflammatory syndrome in children (MIS-C), the pathogenesis of which has not yet been fully elucidated. Here, we comprehensively review and summarize the recommendations and management strategies that have been published to date. Recent Findings: MIS-C patients are treated with different regimens, mostly revolving around the use of immunomodulatory medications, including IVIG and glucocorticoids as first-tier therapy. Refractoriness to IVIG and glucocorticoids warrants a step-up of immunomodulatory therapy to biologic agents such as anakinra, tocilizumab, and infliximab. Summary: We review the current evidence regarding the use of monotherapy versus combination therapy, as well as the current recommendations for assessing thrombotic risk and administering antiplatelet and anticoagulant therapy. We anticipate that future studies will provide evidence for management plans that maximize short- and long-term outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-021-00259-4.

miRNA-148a and miRNA-30c expressions as potential biomarkers in breast cancer patients.

BACKGROUND: Breast cancer is an extensively identified malignant tumor and is a prime cause of cancer mortalities in females. It has been shown that alteration of miRNAs expression (up or down regulation) can affect the initiation and progression of many malignancies. We aimed to evaluate the role of circulating miRNA-148a and miRNA-30c in female patients with breast cancer and estimate their usage as potential biomarkers in the diagnosis, prognosis and survival of breast cancer. METHODS: This study included 75 breast cancer female patients.They were compared with 55 apparently healthy female subjects. miRNAs expression analysis was assessed via real-time PCR. RESULTS: To discriminate breast cancer patients from controls, miR-30c showed the best performance at a cut off value of ≤20.6 (AUC = 0.998, 97.33% sensitivity, 96.36% specificity, p < 0.001), followed by miR-148a (AUC = 0.995, 94.67% sensitivity, 90.91% specificity, p < 0.001 at a cut off value of ≤0.1), CA 15-3 (AUC = 0.930, 88.0% sensitivity, 81.82% specificity, p < 0.001 at a cut off value of >21.3), and finally CEA (AUC = 0.751, 70.67% sensitivity, 63.64% specificity, p < 0.001 at a cut off value of >2.5). CONCLUSION: miRNA-148a and miRNA-30c expressions were down regulated in female patients with breast cancer and might be considered as potential blood biomarkers. Both also might have rule in disease treatment and selection of therapeutic targets. Future studies are needed to improve their role in predicting response to treatment and prognosis.

Spectrum of childhood interstitial and diffuse lung diseases at a tertiary hospital in Egypt.

BACKGROUND: Childhood interstitial and diffuse lung diseases (chILD) encompass a broad spectrum of rare pulmonary disorders. In most developing Middle Eastern countries, chILD is still underdiagnosed. Our objective was to describe and investigate patients diagnosed with chILD in a tertiary university hospital in Egypt. METHODS: We analysed data of consecutive subjects (aged <18 years) referred for further evaluation at the Children's Hospital, Ain Shams University (Cairo, Egypt). Diagnosis of chILD was made in accordance with the ChILD-EU criteria. The following information was obtained: demographic data, clinical characteristics, chest computed tomography findings, laboratory studies, spirometry, bronchoalveolar lavage and histopathology findings. RESULTS: 22 subjects were enrolled over 24 months. Median age at diagnosis was 7 years (range 3.5-14 years). The most common manifestations were dyspnoea (100%), cough (90.9%), clubbing (95.5%) and tachypnoea (90.9%). Systematic evaluation led to the following diagnoses: hypersensitivity pneumonitis (n=3), idiopathic interstitial pneumonias (n=4), chILD related to chronic granulomatous disease (n=3), chILD related to small airways disease (n=3), post-infectious chILD (n=2), Langerhans cell histiocytosis (n=2), idiopathic pulmonary haemosiderosis (n=2), granulomatous lymphocytic interstitial lung disease (n=1), systemic sclerosis (n=1) and familial interstitial lung disease (n=1). Among the subjects who completed the diagnostic evaluation (n=19), treatment was changed in 13 (68.4%) subjects. CONCLUSION: Systematic evaluation and multidisciplinary peer review of chILD patients at our tertiary hospital led to changes in management in 68% of the patients. This study highlights the need for an Egyptian chILD network with genetic testing, as well as the value of collaborating with international groups in improving healthcare for children with chILD.

The diagnostic and prognostic role of MiRNA 15b and MiRNA 378a in neonatal sepsis.

BACKGROUND AND OBJECTIVES: Sepsis is one of the major factors for both term and preterm babies with morbidity and mortality. On the basis of recent clinical trials, altered circulating micro-RNAs (miRNAs) may serve as possible biomarkers in sepsis for diagnosis and prognosis. The aim of this research is to assess the diagnostic and prognostic biomarkers of miRNA 15b and miRNA 378a for neonatal sepsis. SUBJECTS & METHODS: This study was carried out 25 neonates with sepsis admitted to neonatal ICU of Menoufia University Hospital and 25 healthy controls from February 2019 to May 2020. The relative quantification (RQ) of miRNA-15b and miRNA-378a expression was assessed using real time PCR technique. Results: Our results demonstrated that patients with sepsis had significantly higher level of MiRNA-15b than the healthy volunteers. On the other hand, patients with sepsis had significantly lower level of MiRNA-378a than the healthy volunteers. The ROC curve showed that the serum MiRNA-15b was a significant discriminator of sepsis with a combined sensitivity and specificity of 76% and 88% with cutoff point of 3.24. In addition, serum MiRNA-378a was a significant discriminator of sepsis with a combined sensitivity and specificity of 60% and 88% with cutoff point of 0.361. The miRNA-15b expression significantly correlated positive with respiratory rate (r =0.415,p =0.039), WBCs (r = 0.408, p =0.043), and CRP (r =0.407, p=0.043). Likewise, miRNA-378a expression significantly correlated negative with respiratory rate (r =-0.415p =0.024), WBCs (r =- 0.442, p =0.027), and CRP (r =- 0.459, p=0.021). CONCLUSION: Both MiRNA 15b and 378a are promising biomarker for neonatal sepsis.

The "Golden Hours" Algorithm For the Management of the Multisystem Inflammatory Syndrome in Children (MIS-C).

The global concern of increasing number of children presenting with multisystem inflammatory syndrome in children (MIS-C) related to the coronavirus disease (COVID-19) has escalated the need for a case-oriented clinical approach that provides timely diagnosis and management. The aim of this study is to share our experience in managing 64 MIS-C patients of North African ethnicity guided by a risk-based algorithm. Sixty-four patients met the inclusion criteria, 19 (30%) patients were categorized as mild and moderate risk groups and cared for in an isolation ward and 45 patients who belonged to the high-risk group (70%) were admitted to the pediatric intensive care unit (PICU). Positive laboratory evidence of COVID-19 was found in 62 patients. Fever and dysfunction in 2 or more organs were confirmed in all cases (100%). Fifty patients (78%) presented with gastrointestinal symptoms, meanwhile only 10 patients (16%) had respiratory manifestations. Cardiac involvement was reported in 55 (86%) cases; hypotension and shock were found in 45 patients (70%) therein circulatory support and mechanical ventilations were needed for 45 and 13 patients respectively. Intravenous immunoglobulins (IVIG) were used for all cases and methylprednisolone was used in 60 patients (94%). Fifty-eight (91%) patients were discharged home after an average of 9 days of hospitalization. The mortality rate was 9% (6 patients). Conclusion. A single Egyptian center experience in the management of MIS-C patients guided by a proposed bed side algorithm is described. The algorithm proved to be a helpful tool for first-line responders, and helped initiate early treatment with IVIG.

A pilot study on gene expression of endoplasmic reticulum unfolded protein response in chronic kidney disease.

BACKGROUND: 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. OBJECTIVES: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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).

Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder of motile cilia dysfunction generally inherited as an autosomal recessive disease. Genetic testing is increasingly considered an early step in the PCD diagnostic workflow. We used targeted panel next-generation sequencing (NGS) for genetic screening of 33 Egyptian families with clinically highly suspected PCD. All variants prioritized were Sanger confirmed in the affected individuals and correctly segregated within the family. Targeted NGS yielded a high diagnostic output (70%) with biallelic mutations identified in known PCD genes. Mutations were identified in 13 genes overall, with CCDC40 and CCDC39 the most frequently mutated genes among Egyptian patients. Most identified mutations were predicted null effect variants (79%) and not reported before (85%). This study reveals that the genetic landscape of PCD among Egyptians is highly heterogeneous, indicating that a targeted NGS approach covering multiple genes will provide a superior diagnostic yield compared to Sanger sequencing for genetic diagnosis. The high diagnostic output achieved here highlights the potential of placing genetic testing early within the diagnostic workflow for PCD, in particular in developing countries where other diagnostic tests can be less available.

Potential role of MicroRNA 200c gene expression in assessment of colorectal cancer.

BACKGROUND AND AIM: Colorectal cancer (CRC) is a common cancer worldwide that affects men and women of all racial and ethnic groups. Recent evidence supports the role of microRNAs in CRC. We planned to investigate microRNA200c expression and its relation with diagnosis, prognosis, metastasis and overall survival in CRC patients. This study enrolled 90 subjects (3'0 CRC patients, 30 patients with benign colorectal polyps and 30 healthy control subjects). METHODS: Laboratory investigations included measurement of serum CA19-9 and CEA by enzyme linked immunosorbent assay (ELISA) method and relative quantitation (RQ) of microRNA200c gene expression by real time PCR technique. RESULTS: Significant higher MicroRNA200c expression levels in CRC patients versus both benign (P < 0.011) and control groups (P < 0.001), additionally, benign group had elevated levels versus control (P < 0.001). MicroRNA 200c at cutoff >4.56 had sensitivity 86.67% and specificity 73.33% (P < 0.001) for CRC discrimination. Kaplan-Meier survival analysis revealed significant association (P = 0.028) of high expression of microRNA200c with decreased overall survival. CONCLUSION: Noticeable up-regulation of microRNA200c in CRC and its remarkable relation with unfavorable survival suggesting its potential dual use as a diagnostic and prognostic biomarker for CRC.

Biochemical and molecular study on interleukin-1ß gene expression and relation of single nucleotide polymorphism in promoter region with Type 2 diabetes mellitus.

Interleukin-1ß (IL-1ß) assumes a centric role in the regulation of immune and inflammatory responses and thus has been recognized in immune mediated diseases like type 2 diabetes mellitus (T2DM). We aimed to investigate expressed level of IL-1ß and its relation with IL-1ß -511T>C polymorphism in T2DM patients. This study enrolled 80 subjects (50 patients with T2DM and 30 healthy control subjects). Laboratory investigations included fasting (FBG) and 2 h postprandial blood sugar (2 h PBG), HBA1c, lipid profile, and renal function tests. Genotyping of IL-1ß -511T>C (rs16944) SNP assay by real-time PCR and relative quantitation of IL-1ß gene expression transcript by real-time PCR. RESULTS: T2DM patients had significantly higher FBG and 2 h PBG, HBA1c, LDLc, TC, TG, systolic, and diastolic BP while lower HDLc compared with control group. IL 1- ß -511 T>C, CC genotype and C allele were significantly associated with risk of T2DM with odds ratio (OR) 4.73, 95%CI (1.21-18.39) and OR 2.27, 95%CI (1.72-4.40), respectively. Moreover, diabetic patients had significantly higher IL 1- ß gene transcript compared with control group (P < 0.001). CC genotype of IL 1- ß -511 T > C had the highest significant level of IL 1- ß gene transcript demonstrated compared with C/T and T/T genotypes (P < 0.001) in patients. CONCLUSION: C allele of IL-1 ß -511 T >C could be considered risk factor contributor to T2DM and excess level of IL-1 ß transcript may disclose to some degree the inflammatory role of cytokines in T2DM.

Microbial Etiology of Community-Acquired Pneumonia Among Infants and Children Admitted to the Pediatric Hospital, Ain Shams University.

BACKGROUND: While recognizing the etiology of community-acquired pneumonia is necessary for formulating local antimicrobial guidelines, limited data is published about this etiology in Egyptian pediatric patients. OBJECTIVES: To determine the frequency of bacterial and viral pathogens causing community-acquired pneumonia (CAP) among immunocompetent Egyptian infants and preschool children. METHODS: Ninety infants and preschool-age children admitted to our hospital with CAP were prospectively included in the study. Etiological agents were identified using conventional bacteriological identification methods and IgM antibodies detection against common atypical respiratory bacteria and viruses. RESULTS: An etiology was identified in 59 patients (65.5%). Bacterial pathogens were detected in 43 (47.8%) of the cases while viral pathogens were detected in 23 (25.5%). Coinfection with more than one etiologic agent was evident in seven patients (7.8%). The most common typical bacterial cause of pneumonia was Staphylococcus aureus (n = 12, 13.3%), followed by Streptococcus pneumoniae and Klebsiella pneumoniae (n = 7, 7.8%, each). The commonest atypical bacterium was Mycoplasma pneumoniae (n = 10, 11.1%), whereas the commonest viral etiology was influenza viruses (n = 11, 12.2%). CONCLUSION: Although we could not determine the causative agent in some studied cases, this study provides preliminary data regarding the spectrum and frequency of microorganisms causing CAP in Egyptian infants and preschool children.

Serum level of soluble receptor for advanced glycation end products in asthmatic children and its correlation to severity and pulmonary functions.

BACKGROUND: Soluble receptor for advanced glycation end products (sRAGE) acts as a decoy receptor for RAGE which has several distinct pro-inflammatory ligands in the extracellular compartment, and is believed to afford protection against inflammation and cell injury. This study was conducted to measure serum sRAGE in asthmatic children and to assess its correlation with clinical and functional severity and to asthma phenotype according to sputum cytology. METHODS: The study was conducted on 60 asthmatic children from the Pediatric Chest Clinic, Children's Hospital, Ain Shams University. The patients were divided according to asthma control and severity. RESULTS: sRAGE showed statistically significant lower levels in asthmatic patients (899.1 +/- 399.8 pg/mL) compared to the control group (1406.7 +/- 474.3 pg/mL, p = 0.000), with a cut off value of asthma diagnosis of 1080.4 pg/mL with a sensitivity and specificity of 77% and 75%, respectively. Uncontrolled and severe asthmatic subgroups showed lower levels of sRAGE, cut off value of sRAGE for the severity of asthma was 829 pg/mL with 89% sensitivity and 81% specificity. Asthmatic patients stratified according to sputum cytology revealed that those with > 2% eosinophils and > or = 40% neutrophils showed lower levels of sRAGE (710 +/- 258 pg/mL) compared to those with > 2% eosinophils and < 40% neutrophils (1064 +/- 431 pg/mL) (p = 0.000). There was a highly significant positive correlation between sRAGE levels and FEV 1% (r = 0.41, p < 0.01), a highly significant negative correlation with eosinophilic count and total IgE (r = -0.49 and -0.39, respectively, p < 0.01). CONCLUSIONS: Serum level of sRAGE may correlate with severity of bronchial asthma clinically and functionally. It may be a target of future therapeutic interventions.

Genetic variants in vitamin D pathway in Egyptian asthmatic children: a pilot study.

OBJECTIVES: Asthma is a genetically heterogeneous disease. Genetic variants in vitamin D pathway have been reported to be involved with asthma risk. The study aimed to test whether vitamin D binding protein (VDBP or GC-group component) and vitamin D receptor (VDR) gene polymorphisms were associated with asthma characteristics as well as vitamin D level in Egyptian children. DESIGN AND METHODS: The study included 51 asthmatic children and 33 healthy controls of matched sex and age. All participants were genotyped for two SNPs; GC (rs2282679) and VDR (rs2228570) using TaqMan allele discrimination assays. RESULTS: Genotype distribution of GC and VDR showed a significant association with asthma (P = 0.02, P = 0.002). Children carrying the risk "G" allele for GC SNP are 2.22 times more prone to develop asthma [OR = 2.22, 95% CI (1.18-4.2)] whereas those carrying the risk "F" allele for VDR SNP are nearly twice and half times susceptible for asthma development [OR = 2.68, 95% CI (1.36-5.28)] than healthy individuals. For the GC SNP, homozygous children "GG" exhibited significant difference in pulmonary functions (FEV1, FEV1/FVC), asthma severity and asthma control, IgE and vitamin D levels compared to pooled cases of GT and TT genotypes. For the VDR SNP, no significant association between VDR variants and the tested characteristics except for the pulmonary functions where the FEV1/FVC in asthmatic children with "FF " genotype differ significantly from those carrying "Ff"genotype. CONCLUSION: GC and VDR variants may be implicated in asthma susceptibility; hence, further larger studies are still needed to extrapolate our findings to the general population.