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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 FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: A central feature of most cases of bronchiectasis is airway inflammation. The elevated neutrophil count has been strongly correlated with impaired lung function, bronchiectasis severity, and disease duration. There is a failure of resolution of inflammation in bronchiectasis, leading to irreversible damage and dilatation of the bronchial airways with loss of mucociliary function. Lipoxins were the first agents to be identified as anti-inflammatory endogenous lipid mediators involved in the resolution of inflammation. Aim of the Work: This study aimed to measure Lipoxin A4 level in bronchoalveolar lavage (BAL) of children with Cystic Fibrosis bronchiectasis (CF) and Non-CF bronchiectasis as a prognostic marker for clinical and radiological severity in these children as regard Bronchiectasis severity score. Methods: A cross-sectional study was conducted at Children's Hospital, Ain Shams University from December 2020 to December 2021, on children following up at the Pediatric Pulmonology Clinic. The study included 15 patients with cystic fibrosis (CF) bronchiectasis, 15 patients with non-CF bronchiectasis, and 30 control cases, without breathing difficulty or signs of RDS. Human Lipoxin A4 was measured in BAL by ELISA. Results: There was a significant difference between patients and controls as regards Lipoxin A4 level (p = 0.002),being higher in control group, but no significant difference in its level between CF and non-CF bronchiectasischildren(p = 0.663). Conclusion: Severe bronchiectasis is associated with decreased airway Lipoxin A4 levels as lowest level of lipoxinA4 was found in severe cases by bronchiectasis severity score. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 corre-lated 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 (88137) 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 FROM AUTHOR]

OBJECTIVE To assess associations between current use of sodium–glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and their combination and risk for major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS In three nested case-control studies involving patients with type 2 diabetes in England and Wales (primary care data from the Clinical Practice Research Datalink and Secure Anonymised Information Linkage Databank with linkage to hospital and mortality records), we matched each patient experiencing an event with up to 20 control subjects. Adjusted odds ratios (ORs) for MACCE and HF among patients receiving SGLT2i or GLP-1RA regimens versus other combinations were estimated using conditional logistic regression and pooled using random-effectsmeta-analysis. RESULTS Among 336,334 people with type 2 diabetes and without cardiovascular disease, 18,531 (5.5%) experienced a MACCE. In a cohort of 411,206 with type 2 diabetes and without HF, 17,451 (4.2%) experienced an HF event. Compared with other combination regimens, the adjusted pooled OR and 95% CI for MACCE associated with SGLT2i regimens was 0.82 (0.73, 0.92), with GLP-1RA regimens 0.93 (0.81, 1.06), and with the SGLT2i/GLP-1RA combination 0.70 (0.50, 0.98). Corresponding data for HF were SGLT2i 0.49 (0.42, 0.58), GLP-1RA 0.82 (0.71, 0.95), and SGLT2i/GLP-1RA combination 0.43 (0.28, 0.64). CONCLUSIONS SGLT2i and SGLT2i/GLP-1RA combination regimens may be beneficial in primary prevention of MACCE and HF and GLP-1RA for HF. These data call for primary prevention trials using these agents and their combination. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A correction to the article "COVID-19-Related Multisystem Inflammatory Syndrome in Children Presenting With New-Onset Type 1 Diabetes in Severe Ketoacidosis: A Case Series" that was published in a 2022 issue is presented.

Objective: To assess the value of sputum neutrophil elastase as a biomarker of severity in cases of non-cystic fibrosis bronchectasis & cystic fibrosis. Methods: This cross-sectional study was conducted on 50 bronchiectasis patients aged from 1 to 13 years presented to pediatric chest clinic and department of Ain shams university hospital., there were classified into 2 groups; Group A cystic fibrosis patients(30) and group B non-cystic fibrosis bronchiectasis patients(20). Inclusion criteria :children aged from 1 to 16 years, patients were diagnosed with bronchiectasis clinically and with HRCT chest and cystic Fibrosis patients were diagnosed by positive sweat chloride test and genetic study. Exclusion Criteria includes no other known chronic lung diseases. All patients were evaluated by full medical history and full clinical examination, the following lab investigations were done :sweat chloride test, CFTR mutation study, sputum sampling and culture. Quantitative sputum neutrophil elastase assay was done, and the severity of disease was assessed using clinical scores as SK score,FACED score and bronchiectasis severity index and by using radiological scores as Bhalla and modified Reiff score. Results: Steatorrhea was more prevalent among cystic fibrosis patients (80%) than non-CF bronchiectasis patients (0%).(P¼0.00). Clubbing was more prevalent among non -cystic fibrosis bronchectasis (10) (50 %), than cystic fibrosis (2 patients) (6.7 %).(P¼0.00). In cystic fibrosis, neutrophil elastase was significantly higher among severe group (126 ng/mL) than among the moderate (30 ng/mL) and mild (16 ng/mL) groups.(P¼0.00). While in non-CF bronchiectasis patients, neutrophil elastase was significantly higher among severe group (67 ng/mL) than among the moderate (24 ng/mL) and mild (11 ng/mL) groups.(P¼0.00) Conclusion: There was a significant correlation between sputum neutrophil elastase and disease severity in bronchiectasis (both cystic fibrosis and non-CF). [ABSTRACT FROM AUTHOR]

The goal of this study is to investigate the impact of the rs35829419 SNP on the serum level of NLRP3, and to assess the relationship between NLRP3 and its SNP and vulnerability to Pityriasis versicolor. Pityriasis versicolor (PV) is one of the most frequent skin conditions linked to skin pigmentation changes. Malassezia plays a key role in the pathogenesis of PV. A case-control study, 50 patients with pityriasis versicolor and 44 healthy controls. Real-time PCR was used to genotype NLRP3 (rs35829419) and ELISA assay of NLRP3 levels in tissue samples. There was a significantly higher median NLPR3 levels in PV patients than controls. A significant predominance of A allele of Q 705 K was in patients than controls. The risk of having the disease in the presence of A allele is nearly 10 times than having C allele. In PV patients, there was a significant relationship between NLPR3 levels and Q 705 K genotypes with higher NLPR3 levels in AA genotype. A potential correlation between PV and the Q705K polymorphism, pointing to evidence of NLRP3 alteration in PV patients. The NLRP3 inflammasome may be an appropriate therapeutic target for Malassezia-associated skin disorders. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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 2.22times 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]