Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19.

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.

Cytokine profile in Egyptian children and adolescents with COVID-19 pneumonia: A multicenter study.

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.

Association of Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G Polymorphism and Susceptibility to SLE in Egyptian Children and Adolescents: A Multicenter Study.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a key molecule residing at the nexus between thrombosis and inflammatory processes. Recently, PAI-1 and its gene expression have emerged as a potential candidate for autoimmune disorders such as SLE. OBJECTIVE: To investigate whether the PAI-1 4G/5G polymorphism at position -675 could be a genetic marker for susceptibility to childhood-onset SLE and development of lupus nephritis among Egyptian children and adolescents. METHODS: Three hundred fifty patients diagnosed with childhood-onset SLE and 350 well-matched healthy controls were included in this multi-center study. All subjects were genotyped for the PAI-1 promoter 4G/5G polymorphism at position -675 using PCR- restriction fragment length polymorphism (RFLP). Serum PAI-1 levels were measured by ELISA. RESULTS: The PAI-1 (- 675) 4G/4G genotype was more represented in c-SLE patients, as compared to the control group (38% vs 23%; OR =2.7; [95% CI: 1.47-2.9]; P < 0.001). Patients carrying the PAI-1 4G/4G genotype or 4G allele were more likely to develop lupus nephritis (OR: 3.38; [95% CI: 1.9-5.9]; P <0.001, for the 4G/4G genotype and OR: 2.6; [95% CI: 1.85-3.67]; for the 4G allele; P < 0.01). The PAI-1 4G/4G genotype was associated with higher PAI-1 serum concentrations (mean; 86.6±22.7 ng/mL) as compared to those with a 4G/5G genotype (mean; 48.3±16.5 ng/mL) and the lowest for the 5G/5G genotype (mean; 34.7±11.4 ng/mL); P = 0.004. CONCLUSION: The PAI-1 4G/5G polymorphism may confer susceptibility to childhood-onset SLE and development of lupus nephritis among Egyptian children and adolescents. Moreover, the PAI-1 4G/4G genotype and 4G allele were associated with higher PAI-1 serum levels and higher disease activity scores.

Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study.

BACKGROUND: Recently, the interleukin-17A (IL-17A) gene has emerged as a potential candidate gene for autoimmune disorders, including systemic lupus erythematosus (SLE). OBJECTIVES: This study aimed to investigate whether IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T could be susceptibility markers for juvenile-onset SLE (JSLE) and lupus nephritis (LN) in Egyptian children and adolescents. METHODS: In this multi-centre study, we genotyped 320 patients diagnosed with JSLE and 320 matched control children for three IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T using TaqMan probe-based real-time polymerase chain reaction. Meanwhile, IL-17A serum levels were assessed using ELISA. RESULTS: The IL-17 rs2275913 A/A genotype and A allele were more represented in JSLE patients compared to the control group (21% vs. 7%, odds ratio (OR) = 3.8, 95% confidence interval (CI) 1.78-5.5, p = 0.001, pBonf = 0.003 for the A/A genotype; 37% vs. 29%, OR = 1.4, 95% CI 1.11-1.8, p = 0.003, pBonf = 0.009 for the A allele. No significant difference was found for IL-17 rs8193036 and rs3748067 single nucleotide polymorphisms (SNPs) in genotype distribution or allele frequencies (p>0.05). Patients carrying the IL-17 rs2275913 A/A genotype and A allele were more likely to develop LN (OR = 5.64, 95% CI 2.39-13.77, pBonf = 0.001 for the A/A genotype; OR = 2.73, 95% CI 1.84-4.07, pBonf = 0.02 for the A allele). CONCLUSION: The IL-17 rs2275913 A allele and A/A genotype were associated with high IL-17 serum levels and may contribute to susceptibility to JSLE and the development of LN in Egyptian children and adolescents. However, no significant association was evident between the studied IL-17A SNPs and other clinical phenotypes, disease activity scores or laboratory profile of JSLE.

Ficolin-1 gene (FCN1) -144 C/A polymorphism is associated with adverse outcome of severe pneumonia in the under-five Egyptian children: A multicenter study.

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.

Scary gas: pathways in the axial body for soft tissue gas dissection (part I).

Gas is often encountered in abnormal locations in the torso, including within soft tissue compartments, vessels, and bones. The clinical significance of this gas ranges from incidental, benign, and self-limited to aggressive infection requiring immediate surgery. As a result of fascial interconnectivity and pressure differences between compartments, gas can dissect distant from its source. Gas can easily dissect between spaces of the extrapleural thorax, subperitoneal abdomen, deep cervical spaces, and subcutaneous tissues. The pleural and peritoneal cavities are normally isolated but may communicate with the other spaces in select situations. Dissection of gas may cause confusion as to its origin, potentially delaying treatment or prompting unnecessary and/or distracting workup and therapies. The radiologist might be the first to suggest and identify a remote source of dissecting gas when the clinical manifestation alone might be misleading. The purpose of this paper, the first in a three-part series on soft tissue gas, is to explore the various pathways by which gas dissects through the superficial and deep compartments of the torso.

Scary gas: a spectrum of soft tissue gas encountered in the axial body (part II).

Ectopic gas in the mediastinum, subperitoneal abdomen, and superficial soft tissues is concerning and can be seen in the setting of trauma, iatrogenic injuries, infection, and inflammation. It can spread along different dissection pathways and may present remotely from the involved organ as described in part one. Recognition of ectopic gas on imaging and differentiating it from other causes of benign gas is very important as these conditions associated with ectopic gas can lead to rapid patient deterioration and usually require urgent surgery. In part two, the different causes of ectopic and benign gas in the torso are reviewed as well as the imaging features that can help to narrow the differential diagnosis.

Scary gas: intravascular, intracranial, and intraspinal ectopic gas (part III).

While ectopic gas can be a sign of dangerous disease requiring immediate medical or surgical intervention, it can also be an incidental and benign finding. Intravenous gas and spinal vacuum gas are common and almost always benign. Intravascular gas is most often related to instrumentation and, if intraarticular, can cause end-organ ischemia; however, treatment is usually supportive. Pneumocephalus arises from a communication with paranasal sinuses or mastoids more often than from meningeal infection and can usually be managed nonoperatively. In part 3 of this series, the different causes of ectopic gas in the vessels, skull, and spine are reviewed, as are the imaging features that can help to narrow the differential diagnosis.

Evaluation of image registration in subtracted 3D dynamic contrast-enhanced MRI of treated hepatocellular carcinoma.

OBJECTIVE. The objective of our study was to quantify hepatic displacement between breath-holds in multiphasic contrast-enhanced MRI and assess the value of a 3D registration algorithm for displacement correction on subtracted images. MATERIALS AND METHODS. For this retrospective analysis, we evaluated MR images of 25 cirrhotic patients with treated hepatocellular carcinoma (HCC) and at least one coexisting small hepatic cyst that was hypointense on T1-weighted imaging. With the use of an automated 3D deformable registration algorithm, registered base and subtraction images were created using portal venous phase images as the baseline images. The relative displacement of the cysts over the dynamic phases was used to estimate hepatic displacement before and after registration. The width of the subtraction band artifact, HCC lesion conspicuity, and overall subtraction artifact level (i.e., image quality of the entire volume) of the subtraction images were evaluated before and after registration on a 5-point scale (1 = nondiagnostic, 5 = excellent image quality) by two blinded radiologists. Hepatic displacement and subtraction band artifact results were analyzed using the paired Student t test, and the results for HCC lesion conspicuity and image quality of the volume results were analyzed using the Wilcoxon signed rank test. Interobserver agreement was assessed using kappa statistics. RESULTS. The average total cyst displacement on unenhanced, arterial, and delayed phase images was significantly reduced by registration from 4.0, 3.2, and 4.6 mm, respectively, on pre-registered images to 2.4, 1.6, and 1.3 mm on postregistered images (p < 0.01). The mean HCC lesion conspicuity grade improved from 3.4 before registration to 4.4 after registration (p < 0.01), and the mean grade for image quality of the volume improved from 3.3 before registration to 4.6 after registration (p < 0.01). The average width of the subtraction band artifact decreased from 5.3 mm before registration to 2.4 mm after registration, from 6.1 mm before registration to 2.6 mm after registration, and from 5.2 mm before registration to 2.8 mm after registration for the arterial, portal venous, and delayed phase subtractions, respectively (p < 0.01). CONCLUSION. Automated registration of the liver in multiphasic MRI examinations reduced interphasic hepatic displacement, improved the conspicuity of the treated HCC lesion, and improved the overall subtraction image quality.

Diffusion-weighted imaging of the liver: a comprehensive review.

Diffusion-weighted magnetic resonance imaging is based on the Brownian motion of water and enables quantification of the apparent diffusion coefficient throughout the body. This article discusses the principles of diffusion-weighted magnetic resonance imaging, as well as the possible applications and limitations as they apply to liver imaging. This will introduce the readers to this novel magnetic resonance imaging tool, which has a promising future.

Noncontrast functional MRI of the kidneys.

Functional magnetic resonance imaging (fMRI) techniques enable noninvasive assessment of renal function. Diffusion-weighted imaging, diffusion tensor imaging, blood oxygen level-dependent MRI, magnetic resonance elastography, and arterial spin labeling are some of the emerging techniques that have potential to investigate renal function without the use of exogenous gadolinium contrast. This article discusses the principles of these techniques, as well as their possible applications and limitations. This will introduce the readers to these novel imaging tools, which appear to have promising futures.