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BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.
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BACKGROUND: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility. METHODS: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL. RESULTS: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001). CONCLUSIONS: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. IMPACT: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.
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COVID-19 , Receptores de Calcitriol , Deficiência de Vitamina D , Adolescente , Criança , Humanos , COVID-19/genética , Predisposição Genética para Doença , Genótipo , Receptores de Calcitriol/genética , Fatores de Risco , SARS-CoV-2 , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/genéticaRESUMO
Plasma gelsolin (pGSN) correlates with clinical improvement in septic patients. We aimed to investigate pGSN levels as a diagnostic and prognostic marker of neonatal late-onset-sepsis (LOS). A case-control study was done on 184 neonates (92 with LOS and 92 controls). All participants were subjected to detailed history taking, full clinical evaluation, sepsis workup, and pGSN enzyme-linked immunosorbent-assay measurement. We detected significantly lower pGSN level among cases compared to controls (90.63â ±â 20.64 vs 451.83â ±â 209.59). It was significantly related to the severity of sepsis and mortality, with significantly lower values among cases with septic shock and multiorgan failure and non-survivors. Follow-up pGSN significantly increased after sepsis improvement in survivors compared to admission values. pGSN might be a reliable diagnostic and prognostic marker for LOS.
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Sepse Neonatal , Sepse , Recém-Nascido , Humanos , Sepse Neonatal/diagnóstico , Gelsolina , Estudos de Casos e Controles , Sepse/diagnóstico , HospitalizaçãoRESUMO
Background: Most previous studies comparing the effectiveness of Plasma Exchange (PE) or intravenous immunoglobulin (IVIG) in treating Guillain-Barre syndrome (GBS) have focused on the short-term outcome at around 1 month. Objective: To compare the long-term efficacy of PE and IVIG at one year in adult patients with GBS. Methods: Eighty-one adult patients with acute GBS were randomized into two groups with a ratio of 2â:â1: PE (Nâ=â54) and IVIG (Nâ=â27). Patients were assessed with the Medical Research Council sum score (MRC sum score), GBS Disability Scale (GDS), and Functional assessment of acute inflammatory neuropathy (FAAIN) at baseline, ten days, one month, three months, and one year. Neurophysiological examinations were performed at baseline and three months following treatment. Results: There were no significant differences between groups in demographic, clinical, and laboratory data. Both treatments produced a significant improvement in all clinical rating scales in both groups that continued up to one year. There were significant differences in the time course of recovery in the MRC and FAAIN scales, with significantly more improvement in the IVIG group at 1 and 3 months, although there was no significant difference in outcome at one year. However the effect size showed measurable differences between the PE and IVIG groups across the different measures at one-year. Electrophysiological studies showed equal improvement in most measures in both groups at three months, with a slightly greater effect in the IVIG group. Conclusion: long term outcomes of IVIG and PE were equivalent. However the effect size showed measurable differences between the PE and IVIG groups across the different measures at one-year follow-up that indicate the superiorty of IVIG. There was also a tendency for improvement to be slightly faster in the IVIG group.
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Síndrome de Guillain-Barré , Imunoglobulinas Intravenosas , Adulto , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Guillain-Barré/tratamento farmacológico , Troca PlasmáticaRESUMO
This study compared the clinical outcomes of the two main neurophysiological types of Guillain-Barré Syndrome (GBS). Sixty-two GBS patients were examined clinically at onset using Medical Research Council (MRC), Hughes disability scales (HDS), and nerve conduction studies were evaluated in four limbs. The Modified Erasmus GBS outcome score (MEGOS) was assessed 2 weeks after onset. Outcomes were measured after 3 months using MRC and HDS scores. According to electrophysiological data two main groups identified acute inflammatory demyelinating polyneuropathy (AIDP = 31 cases) or acute axonal GBS including inexcitable forms (26 cases). The number of days between onset of weakness and admission was significantly shorter, and gastrointestinal symptoms were significantly higher among the axonal type than AIDP. MRC sum scores at onset and at nadir were significantly worse in the axonal type than in AIDP. Neck muscle weakness, impaired cough reflex, the need for mechanical ventilation, hypoalbuminemia, and hypernatremia were more common in the axonal type. At outcome, 74% of the AIDP were healthy/minor symptoms versus 38.46% of the axonal type. There was a high prevalence of the axonal variant (41.9%) compared with European and North American populations. The axonal type had a significantly worse outcome than AIDP type.
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Síndrome de Guillain-Barré , Humanos , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/terapia , Axônios , Eletrofisiologia Cardíaca , Extremidades , Nível de SaúdeRESUMO
Background: Phototherapy causes oxidative stress which is of particular importance in neonates because of the increased susceptibility of neonatal red blood cell membranes to oxidative damage.Aim: To evaluate the oxidant/antioxidant status in neonates with haemolytic hyperbilirubinaemia before and after exposure to two different intensive phototherapy light sources.Patients and Methods: A randomised controlled study was undertaken in 54 full-term neonates with indirect haemolytic hyperbilirubinaemia admitted to a neonatal intensive care unit in the first week of life. They were randomly divided into two equal groups. Group 1 infants were exposed to intensive conventional phototherapy (Bilisphere 360) and Group 2 were exposed to an intensive light-emitting diode (LED) phototherapy device (Bilitron bed 3600). Total serum bilirubin (TSB), total oxidative stress (TOS), total antioxidant capacity (TAC) and the oxidative stress index (OSI) were measured before and 48 hours after initiation of phototherapy.Results: There was a significant decrease in TSB after phototherapy in both groups (p < 0.001). The TOS and OSI were significantly increased after phototherapy in both groups (p < 0.001) but more so in Group 1 with conventional phototherapy (p = 0.05 and 0.01, respectively). TAC was significantly decreased after phototherapy in both groups (p < 0.00) but more so in Group 1 (p = 0.03).There were significant increases in the incidence of dehydration, hyperthermia and skin rash in the conventional compared with the LED phototherapy group (p = 0.02, 0.01 and 0.02, respectively). However, there was a significant increase in the incidence of hypothermia in the LED compared with the conventional phototherapy group (p = 0.001).Conclusion: Both intensive conventional and LED phototherapy are equally effective in decreasing TSB, but intensive LED phototherapy is safer than intensive conventional phototherapy with regard to oxidative stress and oxidant/antioxidant imbalance.Abbreviations: DSB: direct serum bilirubin; G6PD: glucose-6-phosphate dehydrogenase enzyme; LED: light-emitting diode; OSI: oxidative stress index; TAC: total antioxidant capacity; TOS: total oxidative stresses; TSB: total serum bilirubin.
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Hiperbilirrubinemia Neonatal/terapia , Estresse Oxidativo , Fototerapia/instrumentação , Animais , Feminino , Humanos , Incidência , Recém-Nascido , Iluminação , MasculinoRESUMO
BACKGROUND: Pneumonia is the foremost cause of child death worldwide. M-ficolin is encoded by the FCN1 gene and represents a novel link between innate and adaptive immunity. OBJECTIVES: To investigate the FCN1 -144 C/A (rs10117466) polymorphism as a potential marker for pneumonia severity and adverse outcome namely complications or mortality in the under-five Egyptian children. METHODS: This was a prospective multicenter study that included 620 children hospitalized with World Health Organization-defined severe pneumonia and 620 matched healthy control children. Polymorphism rs10117466 of the FCN1 gene promoter was analyzed by PCR-SSP, while serum M-ficolin levels were assessed by ELISA. RESULTS: The FCN1 A/A genotype and A allele at the -144 position were more frequently observed in patients compared to the control children (43.4% vs 27.6%; odds ratio [OR]: 1.62; [95% confidence interval {CI}: 1.18-2.2]; for the A/A genotype) and (60.8% vs 52.5%; OR: 1.4; [95% CI: 1.19-1.65]; for the A allele); P < .01. The FCN1 -144 A/A homozygous patients had significantly higher serum M-ficolin concentrations (mean: 1844 ± 396 ng/mL) compared with those carrying the C/C or C/A genotype (mean: 857 ± 278 and 1073 ± 323 ng/mL, respectively; P = .002). FCN1 -144 A/A genotype was an independent risk factor for adverse outcomes in children with severe pneumonia (adjusted OR = 4.85, [95% CI: 2.96-10.25]; P = .01). CONCLUSION: The FCN1 A/A genotype at the -144 position was associated with high M-ficolin serum levels and possibly contributes to enhanced inflammatory response resulting in the adverse outcome of pneumonia in the under-five Egyptian children.
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Predisposição Genética para Doença , Lectinas/genética , Pneumonia/genética , Pré-Escolar , Egito/epidemiologia , Feminino , Genótipo , Humanos , Lactente , Lectinas/sangue , Masculino , Razão de Chances , Pneumonia/sangue , Pneumonia/epidemiologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Estudos Prospectivos , Fatores de Risco , FicolinasRESUMO
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
The aim of this work is to study the incidence of acute kidney injury (AKI) in neonates admitted to the neonatal intensive care unit (NICU) over a six-month period from September 2011 to March 2012. This prospective study was performed on 250 neonates admitted to the NICU at the Children's Hospital, Faculty of Medicine, Zagazig University. All neonates were subjected to detailed history taking, including pre-natal, natal and post-natal history, with stress on symptoms suggestive of AKI. All neonates were examined thoroughly and the following investigations were performed: Blood urea nitrogen (BUN), serum creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27 cases (10.8%), including 12 females and 15 males. 40.7% of the AKI cases were born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI cases had oliguria, and there was male sex predominance, with a male-female ratio of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of the cases. The predisposing factors for AKI were sepsis in 63% of the cases, respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri-natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%, congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that pre-renal failure was the most common form of AKI in our patients. Early recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative problems and rapid effective treatment of contributing conditions will reduce the incidence of AKI in the neonatal period.