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BACKGROUND: To date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID-19) has not been reported. OBJECTIVES: We investigated serum levels of a panel of key cytokines in children and adolescent with COVID-19 pneumonia with a primary focus on "cytokine storm" cytokines such as interleukin (IL)-1ß, IL-6, IL-17, IL-2, IL-4, IL-10, interferon (IFN-γ), tumor necrosis factor (TNF)-α, and two chemokines interferon-inducible protein-10 (IP-10) and IL-8. We also studied whether these cytokines could be potential markers for illness severity in COVID-19 pneumonia. METHODS: Ninety-two symptomatic patients aged less than 18 years with confirmed COVID-19 pneumonia and 100 well-matched healthy controls were included in this multi-center study. For all patients, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory fluid specimens was detected by real-time reverse-transcriptase polymerase chain reaction. We measured serum concentrations of studied cytokines by using flow cytometry. RESULTS: Patients with COVID-19 had significantly higher median IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 serum levels than did control children (all p < 0.01). Patients with severe COVID-19 pneumonia had significantly higher median IL-1ß, IL-6, and IP-10 serum levels as compared with those with moderate COVID-19 pneumonia; all p < 0.01. ROC analysis revealed that three of the studied markers (IL-6, IL-1ß, and IP-10) could predict severe COVID-19 pneumonia cases with the largest AUC for IL-6 of 0.893 (95% confidence interval: 0.84-0.98; p < 0.01). CONCLUSION: Our study shows that pediatric patients with COVID-19 pneumonia have markedly elevated serum IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 levels at the initial phase of the illness indicating a cytokine storm following SARS-CoV-2 infection. Moreover, serum IL-6, IL-1ß, and IP-10 concentrations were independent predictors for severe COVID-19 pneumonia.
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COVID-19 , Citocinas/sangue , Adolescente , COVID-19/imunologia , Criança , Egito/epidemiologia , HumanosRESUMO
BACKGROUND: Assessment of the left ventricular function in the dialysis children and explore its association with vitamin D level and markers reflecting calcium and phosphate metabolism. METHODS: In this case-control study, we enrolled forty children on regular hemodialysis and forty healthy controls from July 2019 to March 2020 at the pediatric dialysis unit. Echocardiographic evaluation using both conventional and Tissue Doppler Imaging (TDI) was done for all subjects. Vitamin D and its markers were analyzed to assess its association with ventricular dysfunction. RESULTS: Diastolic function in children on hemodialysis was significantly impaired as evidenced by lower Mitral E/A velocity ratio (E/A), lower early diastolic velocity (E'), and higher E/E' ratio (Ratio of early diastolic mitral inflow velocity (measured by pulsed wave traditional Doppler) to early diastolic mitral annular velocity (measured by Tissue Doppler). in comparison with the controls. Most end stage renal disease (ESRD) participants had vitamin D deficiency. There was an important correlation between left ventricular (LV) dysfunction and both Vitamin D deficiency and hyperparathyroidism. Although our patients had normal systolic function by conventional and Tissue Doppler echocardiographic study, mean values of TDI- MPI (Mean Performance Index) in the haemodialysis group were significantly higher than in the control group, which indicates impaired global cardiac systolic and diastolic function. CONCLUSIONS: Tissue Doppler Imaging (TDI) provides a good reflection of the LV diastolic function. As vitamin D deficiency has been substantially associated with worsening of LV dysfunction, we suggest that TDI and Vitamin D might be included in the routine follow-up of pediatric dialysis patients.
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BACKGROUND: Acute lower respiratory infection (ALRI) is the leading cause of child mortality, especially in the developing world. Polymorphisms in the interleukin 4 (IL-4) gene have been linked to a variety of human diseases. OBJECTIVES: To investigate whether the IL-4 -590C/T (rs2243250) polymorphism could be a genetic marker for susceptibility to ALRIs in young Egyptian children. METHODS: This was a multicenter study conducted on 480 children diagnosed with pneumonia or bronchiolitis, and 480 well-matched healthy control children. Using PCR-RFLP analysis, we genotyped a -590C/T (rs2243250) single nucleotide polymorphism of the IL-4 gene promoter, meanwhile the serum IL-4concentration was measured by ELISA. RESULTS: The frequency of the IL-4 -590 T/T genotype and T allele were overrepresented in patients with ALRIs in comparison to the control group (OR = 2.0; [95% confidence interval [CI]: 1.38-2.96]; for the T/T genotype) and (OR: 1.3; [95%CI: 1.07-1.56]; for the T allele; P < 0.01). The IL-4 -590 T/T genotype was associated with significantly higher mean serum IL-4 concentration (58.7 ± 13.4 pg/mL) compared to the C/T genotype (47.6 ± 11 pg/mL) and the C/C genotype (34.8 ± 9.6 pg/mL); P < 0.01. CONCLUSION: The IL-4 -590C/T (rs2243250) polymorphism may contribute to susceptibility to ALRIs in young Egyptian children.
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Bronquiolite/genética , Predisposição Genética para Doença , Interleucina-4/genética , Pneumonia/genética , Infecções Respiratórias/genética , Alelos , Bronquiolite/sangue , Pré-Escolar , Egito , Feminino , Genótipo , Humanos , Lactente , Interleucina-4/sangue , Masculino , Pneumonia/sangue , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Infecções Respiratórias/sangueRESUMO
BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of child deaths around the world. Recently, the vitamin D receptor (VDR) gene has emerged as a susceptibility gene for CAP. OBJECTIVES: To evaluate the association of the VDR gene Fok I polymorphism with susceptibility to CAP in Egyptian children. METHODS: This was a multicenter case-control study of 300 patients diagnosed with CAP, and 300 well-matched healthy control children. The VDR Fok I (rs2228570) polymorphism was genotyped by PCR-restriction fragment length polymorphism (RFLP), meanwhile serum 25-hydroxy vitamin D (25D) level was assessed using ELISA method. RESULTS: The frequencies of the VDR FF genotype and F allele were more common in patients with CAP than in our control group (OR = 3.6; (95% CI: 1.9-6.7) for the FF genotype; P = 0.001) and (OR: 1.8; (95% CI: 1.4-2.3) for the F allele; P = 0.01). Patients carrying the VDR FF genotype had lower serum (25D) level (mean; 14.8 ± 3.6 ng/ml) than Ff genotype (20.6 ± 4.5 ng/ml) and the ff genotype (24.5 ± 3.7 ng/ml); P < 0.01. CONCLUSION: The VDR gene Fok I (rs2228570) polymorphism confers susceptibility to CAP in Egyptian children.
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Infecções Comunitárias Adquiridas/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Predisposição Genética para Doença , Pneumonia/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Egito , Feminino , Humanos , Lactente , Masculino , Pneumonia/sangue , Estudos Prospectivos , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of childhood morbidity and mortality worldwide. The angiotensin-converting enzyme (ACE) gene is a potential candidate gene for CAP risk. OBJECTIVES: In this study, we aimed to investigate whether the ACE insertion/deletion (I/D) polymorphism (rs4340) could be a genetic marker for CAP susceptibility in Egyptian children, and we also measured the serum ACE level to assess its relation to such polymorphism. METHODS: This was a prospective case-control study included 300 patients with CAP, and 300 age, gender, and ethnicity matched healthy controls. The ACE I/D polymorphism (rs4340) at intron 16 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum ACE levels were measured by ELISA. RESULTS: Compared to the controls subjects, the frequencies of the ACE DD genotype and D allele were overrepresented in patients with CAP (OR = 3.05; [95%CI: 2.14-4.35] for the DD genotype; P < 0.001) and (OR: 1.8; [95%CI: 1.42-2.29]; for the D allele; P < 0.01, respectively). Patients with the DD genotype had significantly higher mean serum ACE levels (45.6 ± 11.4 U/L) compared to those with ID genotype (36.5 ± 8.3 U/L) and II genotype (21.6 ± 5.7 U/L); P < 0.01, respectively. CONCLUSION: The ACE I/D polymorphism (rs4340) may contribute to the genetic susceptibility of CAP in Egyptian children. The ACE D allele and DD genotype were associated with higher serum ACE levels among studied CAP patients.
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Infecções Comunitárias Adquiridas/genética , Peptidil Dipeptidase A/genética , Pneumonia/genética , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/epidemiologia , Egito/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Peptidil Dipeptidase A/sangue , Pneumonia/sangue , Pneumonia/epidemiologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Estudos ProspectivosRESUMO
Febrile seizure is the most common seizure disorder of childhood. Of the pro-inflammatory cytokines, interleukin-1 is defined as the first endogenous pyrogen.We designed this study to investigate single-nucleotide polymorphisms (SNPs) situated at positions -31â(C/T), and -511â(C/T) of interleukin-1beta (IL-1ß) gene promoter and interleukin-1receptor antagonist (IL-1RA) gene variable number of tandem repeats in intron 2 (VNTR); to determine whether these polymorphisms could be a marker of susceptibility to febrile seizures in Egyptian children and we also measured the serum level of IL-1ß to assess its relation to such polymorphisms.This was a case-control study included 155 patients with febrile seizure, and matched with age, sex, ethnicity 155 healthy control subjects. IL-1ß promoter at positions -31â(C/T), -511â(C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1ß levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1ß-511 TT genotype and T allele at the same position were observed to be increased in patients with febrile seizures (FS) compared with the control group (odds ratio [OR]: 3.96; 95% confidence interval [CI]: 1.68-9.5; Pâ=â0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18-2.3; Pâ=â0.003 for the T allele, respectively). The IL-1 RA II/II homozygous variant and IL-1 RA allele II were overrepresented in patients with FS than control group (OR: 4.02; 95% CI: 1.78-9.15; Pâ=â0.001and OR: 1.73; 95% CI: 1.24-2.4; Pâ=â0.001, respectively). We found a significant positive association between the IL-1 RA II/II genotype and susceptibility to FS in sporadic cases as did allele II at the same position (OR: 5.04; 95% CI: 2.1-12.5 for the IL-1 RA II/II genotype; Pâ=â0.001) and (OR: 1.94; 95% CI: 1.3-2.8 for the allele II; Pâ=â0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1ß compared with those with other genotypes and alleles.We demonstrate for the first time that the presence of a T allele or TT genotype at -511 of IL-1ß promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.
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Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Convulsões Febris/genética , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Egito/epidemiologia , Feminino , Genótipo , Humanos , Lactente , Masculino , Razão de Chances , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genéticaRESUMO
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.
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BACKGROUND: Protrusion of the patent ductus arteriosus (PDA) stent can occur into the lumen of the main pulmonary artery (MPA) branch, the aorta, or both. This protrusion can vary from trivial to major, causing potential obstruction to the vessel lumen, which may cause flow obstruction or risk of thromboses. As far as we know, no one has followed these patients with protruding stents to see whether they do pose a risk of obstruction or thromboses. METHODS: A retrospective, descriptive, cross-sectional study reviewing charts of all included patients who received stents in the MPA branches with residual protrusion into the pulmonary artery branch lumen (total, 87 patients; 34 patients with protruding stents) was performed to determine whether this protrusion caused any undesired effects on flow or coagulation. The patients were divided into two groups: the protruding stents group (group 1); and the non-protruding stent group that served as a control group (group 2). Each group was then categorized into 3 sections according to the stent position, the PDA, the MPA branches, and the Blalock-Taussig shunt. RESULTS: The only risk factor that had statistical significance was the number of stents in the PDA site. CONCLUSION: Protruding stents do not cause an increased risk of thrombosis in patients on aspirin. Mild protrusion is more likely in PDA stents and severe protrusion is more likely in the MPA branch stents. Severe protrusion is more likely when more stents are used in the PDA location. There is no statistical evidence that protrusion can cause lung perfusion defects from the small numbers we have.