Role of interleukin 6 polymorphism and inflammatory markers in outcome of pediatric Covid- 19 patients.

BACKGROUND: IL-6 polymorphisms were associated to viral infection outcomes through affection of IL-6 production and it is an early indicator of tissue injury and systemic inflammatory response. The study aimed to determine whether genetic IL-6 polymorphisms, serum interleukin-6 level and inflammatory markers (Presepsin, CXCL-10, C3, and C4) are associated with the prediction of disease severity in pediatric COVID-19 patients and its possible use as a prognostic tool in pediatric patients admitted to hospital. METHODS: This prospective cohort study was conducted on 150 children with COVID-19. Patients were divided according to the severity of infection into four groups: group I (mild) 67 cases; group II (moderate) 53 cases, group III (severe) 17 cases and group IV (critical) 14 cases. Serum Interleukin 6, CXCL-10, Presepsin, renal and liver functions, electrolytes, C3, C4, ferritin, and D dimer serum levels were assessed in all patients. The Kruskal Wallis test used to compare parametric quantitative data between studied groups and Mann Whitney test for each pair of groups. Non-parametric quantitative data was compared between studied groups using a one-way ANOVA test and post-hoc Bonferroni analysis for each pair of groups. RESULTS: Group I: 35 males and 32 females with a median age of 16 months. Group II: 17 males and 35 females with a median age of 13 months. Group III: 6 males and 11 females with a median age of 12 months and group IV: 3 males and 11 females with a median age of 12 months. There was no statistical difference between the studied groups regarding gender and age. Serum levels of IL- 6, serum ferritin; D-dimer, Presepsin and CXCL 10 were significantly higher in both severe and critical groups than the other 2 groups (mild and moderate). ROC curve analysis showed that interleukin-6 and Presepsin were good markers for prediction of severity of COVID-19 among the diseased children. For severe cases, the sensitivity of interleukin-6 was 76.47% and specificity was 92.31%. For critical cases, the sensitivity of interleukin-6 was 71.43% and specificity was 82.35%. The sensitivity of Presepsin was 76.47% and specificity was 88.46% in severe cases. For critical cases, the sensitivity of Presepsin was 78.57% and specificity of 91.2%. There was significant difference in IL-6 572 allelic among moderate cases with the most frequent 42.3% for genotype (GC) and allelic among severe cases with the most frequent 47.1% for genotype (GC). Significant difference in IL-6 174 allelic among critical cases with the most frequent 78.6% for genotype (CC). CONCLUSIONS: Children whom expressed GC genotypes of IL6 (-572G > C) polymorphism are at a considerably higher risk of developing a severe disease. This risk is significantly larger in the severe group of children than in children in critical condition who have GC genotypes of IL6 (-174 G > C) polymorphism. While IL6 (-597G > A) polymorphism has no role in COVID 19 severity in children.

Assessment of serum proprotein convertase subtilisin/kexin type 9 in pediatric sepsis syndrome.

Sepsis is a life-threatening condition that arises when the body's response to infection causes injury to its tissues and organs. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme released in response to the drop in cholesterol level occurring in sepsis. Our study aimed to evaluate the prognostic role of serum Proprotein convertase subtilisin/kexin type 9 (PCSK9) level in children with sepsis and severe sepsis. Sixty children were included in this study. They were divided into two groups: 30 children in the sepsis group and 30 in the severe sepsis group. Another 30 apparently healthy children were included as a control group. Blood samples were withdrawn from all included children for complete blood count (CBC), renal function tests (RFT), liver function tests (LFT), LDL-cholesterol (LDL-C), blood culture, and serum PCSK9. In this study, PCSK9 and LDL-C were higher in the two sepsis groups than in the control group (p < 0.05). They were also higher in the severe sepsis group than the sepsis group and in the non-survivors than in the survivors (p < 0.05). PCSK9 was positively correlated with length of hospital stay in surviving children (r = 0.67, p = 0.001) and had predicted significant hematological dysfunction (adjusted B = - 96.95, p = 0.03). In conclusion, the PCSK9 assay can be used as a biomarker for bad prognosis in children suffering from clinical sepsis.

Thrombophilia genetic mutations and their relation to disease severity among patients with COVID-19.

OBJECTIVES: Patients with COVID-19 infection appear to develop virus-induced hypercoagulability resulting in numerous thrombotic events. The aim of the present study was to determine the relationship between the thrombophilia genes mutations (prothrombin G20210A, factor V Leiden, and methyltetrahydrofolate reductase (MTHFR)) and the severity of COVID-19 patients. DESIGN: Prospective cross-sectional study. METHOD: One hundred and forty patients (80 adults and 60 children) were included in the current study. They were divided into the severe COVID-19 group and the mild COVID-19 group, with each group comprising 40 adults and 30 children. The patients were assessed for FV R506Q, FV R2H1299R, MTHFR A1298C, MTHFR C677T, and prothrombin gene G20210A polymorphisms. CBC, D-dimer, renal and liver function tests, hs-CRP, ferritin, and LDH were also assessed. Thrombotic events were clinically and radiologically documented. RESULTS: Severe COVID-19 cases were significantly more frequent to have a heterozygous mutation for all the studied genes compared to mild COVID-19 cases (p<0.05 for all). Being mutant to gene FV R506Q carried the highest risk of developing a severe disease course (p<0.0001). Patients with abnormally high D-dimer levels were significantly more frequent to be heterozygous for FV R506Q, FV R2H1299R, and prothrombin gene G20210A (p = 0.006, 0.007, and 0.02, respectively). CONCLUSION: We concluded that there is an evident relationship between severe COVID-19 and inherited thrombophilia. In the current study, FV R506Q gene mutation carried the highest risk of developing a severe COVID-19 disease course.

Red cell distribution width as a prognostic marker for complications of community-acquired pneumonia in children: a comparison with Proadrenomedullin and Copeptin.

BACKGROUND: Community-acquired pneumonia (CAP) is the most common leading cause of morbidity and mortality in children; so, early identification of patients with CAP, who are at risk of complications or high mortality, is very critical to identify patients who need early admission to the intensive care unit. PURPOSE OF THE STUDY: To explore the prognostic value of Red Cell Distribution Width (RDW), Proadrenomedullin and Copeptin in the prediction of complicated CAP in children. METHODS: 99 children were enrolled in the study, which was done at the Pediatric Department of Minia University Hospital. Measurement of serum Proadrenomedullin, Copeptin, and RDW was done to all participating children in the first 24 h of admission. Assessment of the severity of CAP was done using the Pediatric Respiratory Severity Score (PRESS). RESULTS: The values of RDW, Proadrenomedullin, and Copeptin were significantly higher in the complicated CAP group than in the uncomplicated one (P value < 0.01). There were significant positive correlations between RDW and Proadrenomedullin with PRESS (r 0.56 for both). For the prediction of complications, RDW at cutoff point > 17.4, has 77.7% of sensitivity and 98.6% of specificity, followed by Pro ADM at cutoff point > 5.1 nmol/L, of 74% of sensitivity and 90.2% of specificity. For the prediction of mortality, RDW at cutoff point > 17.4 has 81.25% of sensitivity and 89.16% of specificity. CONCLUSION: The RDW is a reliable predictor of poor outcomes in pediatric CAP.

Serum miRNA-21, miRNA-146a and plasma cell free DNA as novel biomarkers for assessing systemic lupus erythematosus activity.

BACKGROUND: MicroRNA and cell-free DNA have shown significant correlations with several autoimmune disorders including systemic lupus erythematosus (SLE). SLE has been associated with challenges in determining its activity, so that the need for biomarkers contributing to assessing its activity is emerging. The current study investigated miRNA-21, miRNA-146a and plasma cf-DNA in determination of SLE activity, in addition their association with clinical data including complement factor 3 (C3), complement factor(C4), anti-dsDNA, and other disease activity indices. METHODS AND RESULTS: Eighty subjects divided into; twenty active patients (with SLE-DAI2K score of 16-18) twenty inactive patients (with SLE-DAI2K score of 1-3), and forty healthy control participants) were included in this study. Serum miR-21, miR-146a, and plasma cf-DNA were quantified by real time PCR and their correlation with clinical data was statistically analyzed. The results demonstrated that active cases have significant upregulation of serum miRNA-21 and plasma cf-DNA. Moreover, miR-21 showed a negative, significant pertaining to C3, C4 and was positively related to Systemic Lupus Erythematosus Disease Activity Index 2 K score (SLE-DAI Index2K score) and Systemic-Lupus-Erythematosus-Disease Activity-Index 2 K activity (SLE-DAI 2 K activity). Also, Active group miRNA-146a was negatively, significantly correlated with C3, as well as a positive significant relationship with SLE-DAI2K score and SLEDAI 2 K activity, in addition to anti DNA Autoantibodies. Furthermore, miR-21 and cf-DNA demonstrated a differential value through Receiver Operating Characteristic (ROC) curve's study. CONCLUSIONS: the present study illustrated miR-21, miR-146a, and cf-DNA relationship with SLE clinical data. In addition to their potential value in SLE diagnosis, and activity determination.

Detection of hepatitis C virus (HCV) RNA in the peripheral blood mononuclear cells of HCV-infected patients following sustained virologic response.

It is unclear whether direct-acting antiviral drugs (DAAs) result in the complete eradication of HCV infection or whether some quantities of the virus may persist after achieving a sustained virologic response (SVR). Aim The aim of this work was to study the possibility of the persistence of HCV RNA in peripheral blood mononuclear cells (PBMCs) after achieving SVR following DAA treatment. This study included 100 patients infected with HCV genotype 4, who were candidates for receiving DAAs and who achieved SVR during follow-up, as determined at 12 and/or 24 weeks following the end of treatment. All patients were subjected to demographic, biochemical and hematological assessments. Detection of HCV RNA in the serum and PBMCs and determination of the HCV genotype were performed with real-time PCR. We detected HCV RNA in the PBMCs of 20 out of 100 (20%) patients infected with HCV genotype 4, who achieved SVR. However, the persistent viral load in the PBMCs was very low (range: 400-900 U/mL; mean ± SD: 645.45 ± 153 U/mL). Multiple logistic regression analysis showed that only the higher posttreatment levels of aspartate transaminase (AST) were significantly predictive of HCV RNA persistence in the PBMCs (OR: 1.29; 95% CI: 1.08-1.55). Additionally, according to the Cox proportional hazard model, liver cirrhosis was the only significant risk factor for the persistence of HCV infection in PBMCs (HR: 5.8; 95% CI: 1.3-26.1; P < 0.02). Our results indicated the persistence of HCV RNA in some HCV patients who achieved SVR after treatment with DAAs.

Assessment of early kidney injury caused by asymptomatic bacteriuria in children with type 1 diabetes.

INTRODUCTION: Infection is one of the most frequent causes of morbidity and mortality in diabetic patients. Some microorganisms become more virulent in a high glucose concentration. Diabetics are more likely to have asymptomatic and symptomatic bacteriuria. NGAL is secreted in high concentrations into the blood and urine within two hours of AKI. OBJECTIVES: The aim of the study is early detection of UTI in type1diabetic children through screening of their urine samples, and measurement of NGAL urinary levels in cases with asymptomatic bacteriuria for early detection of AKI to prevent serious complications. PATIENTS AND METHODS: One thousand twenty-two known diabetic children on regular follow up in endocrine outpatient clinic at Minia Children University hospital were screened for UTI. From them only 52 diabetic children were diagnosed as asymptomatic bacteriuria (group I), 52 diabetic children with normal urine analysis (group II) and 52 apparently healthy children, age and sex matched, served as controls (group III). CBC, Renal function test, HbA1c, hs- CRP, Albumin/creatinine ratio, urine examination, urine culture, GFR and urinary NGAL were done to all children. RESULTS: Thirty-seven females (71.2%) had asymptomatic bacteriuria, Hs CRP and urinary NGAL were significantly higher, while GFR was significantly lower in diabetic children with bacteriuria than the other two groups. For diabetic children with bacteriuria, (AUC) for NGAL was 1 with optimal cutoff value of > 44.1 (Sensitivity 100% and Specificity 100%) while AUC for hsCRP was 0.887 with optimal cutoff value of > 1 (Sensitivity 82.69% and Specificity 90.38%). CONCLUSION: Routine urine analysis should be done for all diabetic children even if they are asymptomatic. NGAL and hsCRP are non-invasive methods that could detect early renal injury in these patients thus, early, and proper management of UTI should be started to prevent renal injury.

Serum and Synovial Fluid Levels of Interleukin-17A in Primary Knee Osteoarthritis Patients: Correlations With Functional Status, Pain, and Disease Severity.

Objectives: This study aims to assess the serum and synovial fluid (SF) levels of interleukin (IL)-17A in primary knee osteoarthritis (KOA) patients and to study their correlations with functional status, pain, and disease severity. Patients and methods: This cross-sectional study was conducted between December 2017 and March 2018 and it included 70 patients (46 males, 24 females; mean age 57.3±10.0 years; range 34 to 76 years) with primary KOA and 30 age-, sex-, and body mass index-matched healthy individuals (20 males, 10 females; mean age 53.3±10.3 years; range, 35 to 70 years). Western Ontario and McMaster Universities osteoarthritis index (WOMAC), visual analog scale (VAS), Lequesne index, and Kellgren and Lawrence (KL) grading scale were used for assessment of the disease. IL-17A levels were measured in the serum for patients and healthy controls, and in SF for patients only using an enzyme-linked immunosorbent assay. Results: Serum levels of IL-17A were significantly higher in KOA patients than controls (p=0.04). A positive correlation was found between serum and SF IL-17A levels. Serum and SF IL-17A levels had positive correlations with VAS, WOMAC pain score, Lequesne pain score, WOMAC function score, and Lequesne index. SF IL-17A levels had strong positive correlations with radiographic severity (KL grade) and duration of OA. Conclusion: Higher IL-17A levels in primary KOA patients were significantly associated with longer disease duration, higher pain scores, worse quality of life, extreme disability, and advanced structural damage. Therapeutics that target IL-17A warrant further investigation.

The effect of zinc deficiency and iron overload on endocrine and exocrine pancreatic function in children with transfusion-dependent thalassemia: a cross-sectional study.

BACKGROUND: Children with transfusion-dependent thalassemia (TDT) suffer from secondary hemosiderosis and the delirious effects this iron overload has on their different body organs, including the pancreas. They are also more prone to develop zinc deficiency than the general pediatric population. This study aimed to determine the effect of zinc deficiency and iron overload on the endocrine and exocrine pancreas in TDT children. METHODS: Eighty children, already diagnosed with TDT, were included in this study. We assessed the following in the participant children: serum ferritin, serum zinc, endocrine pancreatic function (oral glucose tolerance test (OGTT), fasting insulin level and from them, HOMA-IR was calculated), and exocrine pancreatic function (serum lipase and serum amylase). RESULTS: Forty-four TDT children had a subnormal zinc level, while 36 of them had a normal serum zinc level. TDT children with low serum zinc had significantly more impaired endocrine pancreatic function and an abnormally high serum lipase than children with normal serum zinc, p < 0.05 in all. Serum zinc was significantly lower in TDT children with serum ferritin above the ferritin threshold (≥2500 ng/ml) than those below (59.1 ± 20.2 vs. 77.5 ± 28.13), p = 0.02. TDT children, having a serum ferritin ≥2500 ng/ml, had significantly more frequently impaired endocrine pancreatic function and abnormally high serum lipase than TDT children below the ferritin threshold, p < 0.05 in all. CONCLUSION: In children with transfusion-dependent thalassemia, zinc deficiency aggravates iron-induced pancreatic exocrine and endocrine dysfunction.

Gastric antral vascular ectasia in hepatitis C virus related liver cirrhosis: Fetching for predictors.

BACKGROUND AND AIM: Gastric antral vascular ectasia (GAVE) is observed in patients with liver cirrhosis and portal hypertension. The exact pathophysiologic mechanism that underlies this condition is unknown. In our study, we estimate the prevalence of GAVE in hepatitis C virus (HCV) cirrhosis and attempted to determine if any of the hepatocellular manifestations, liver functions, serum gastrin, abdominal ultrasound and endoscopic picture have a relation to, or could predict, the occurrence of GAVE in cirrhotic patients. METHODS: This study includes 500 HCV-related liver cirrhosis patients. According to endoscopic assessment, we detected 30 patients with GAVE (Group 2). From the 470 patients without GAVE, we randomly selected 120 patients (Group 1), to avoid statistical bias, for comparison with Group 2. Comparison included clinical manifestations, laboratory findings, serum gastrin, ultrasound findings, and endoscopic findings (esophageal and/or gastric varices and gastropathy). RESULTS: The percentage of GAVE in HCV-related liver cirrhosis is 0.06%. We can predict GAVE by platelets, palmer erythema, diabetes mellitus (DM), marked ascites > with area under the curve of 0.67, 75.5, 0.62, and 0.40%, and accuracy of 82.5, 72, 70.7, and 79.3%, respectively. There was no correlation found between occurrence of GAVE and endoscopic findings. Also, there was no correlation found between occurrence of GAVE and serum gastrin levels, which reflect another pathophysiology, and we found no statistically significant correlation with GAVE. CONCLUSIONS: Palmer erythema, low platelets, DM, and ascites might help in the prediction of GAVE. GAVE is not linked to the presence, type or grade of varices, and gastropathy.

Admission platelet count and indices as predictors of outcome in children with severe Sepsis: a prospective hospital-based study.

BACKGROUND: Sepsis is still one of the main causes of infants and children mortality especially in developing, economically challenged countries with limited resources. Our objective in this study was to determine, the prognostic value of platelet count, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) in critically ill infants and children with severe sepsis, as they are readily available biomarkers, that can guide clinicians during managing of severe sepsis. METHODS: Sixty children were included; they were diagnosed with severe sepsis according to the international pediatric sepsis consensus conference criteria. At admission to Pediatric intensive care unit, complete blood count with platelet count and parameters (MPV, PDW and PCT) and C-reactive protein (CRP) level were determined for all children. Also, assessment of the Pediatric Risk of Mortality (PRISM III) score was done to all. These children were followed up till discharge from hospital or death. Accordingly, they were grouped into: (1) Survivor group: included 41 children. (2) Non-survivor group: included 19 children. RESULTS: Platelet count and PCT were significantly lower (p < 0.001) and MPV was significantly higher in non-survivor than survivors (p = 0.004). MPV/PLT, MPV/PCT, PDW/PLT, PDW/PCT ratios were found to be significantly higher in the non-survivors than survivor (p < 0.001 in all). PCT with sensitivity = 94.74%, was the most sensitive platelet parameter for prediction of death, while MPV/PCT was the most sensitive ratio (sensitivity = 94.7%). CONCLUSION: Thrombocytopenia, platelet indices and their ratios, especially plateletcrit and MPV/PCT, are readily available, sensitive, prognostic markers, that can identify the severe sepsis patients with poorest outcome.

Clinical significances and diagnostic utilities of both miR-215 and squamous cell carcinoma antigen-IgM versus alpha-fetoprotein in Egyptian patients with hepatitis C virus-induced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It has been widely established that the early detection of HCC enables more treatment options with improvements in prognosis and survival. OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of both circulating miR-215 and squamous cell carcinoma antigen-IgM (SCCA-IgM) as serum biomarkers for HCC by examining their diagnostic sensitivity, specificity, accuracy, and predictive values in hepatitis C virus (HCV)-induced HCC patients. SUBJECTS AND METHODS: This study included 60 patients with HCV-related HCC. In addition, 60 patients with HCV-related liver cirrhosis (LC) and 60 apparently healthy subjects were involved, and served as diseased and healthy control groups, respectively. The relative expression levels of miR-215 were detected using quantitative real-time PCR. SCCA-IgM levels in serum were measured by enzyme immunoassay. We used receiver operating characteristic (ROC) curve to calculate the diagnostic accuracy against alpha-fetoprotein (AFP). RESULTS: Relative miR-215 expression levels increased the most in HCC patients compared to that in healthy or diseased controls (P<0.001). Serum concentration of SCCA-IgM was significantly higher in HCC group than that in the two control groups. We performed multivariate analysis using AFP level, focal lesion size, and portal vein thrombosis as independent variables. ROC curves showed that the optimum diagnostic miR-215 cutoff value for identifying HCC patients from cirrhotic ones was 417 (sensitivity, 97%; specificity, 91%) and for SCCA-IgM was 95 AU/mL (sensitivity, 92%; specificity, 98%). Moreover, the superiority of both miR-215 and SCCA-IgM to AFP is obvious in our study and this superiority is more evident in distinguishing HCC with AFP levels <200 ng/mL and HCC patients with small-sized focal lesions from cirrhotic patients. CONCLUSION: Cell-free miR-215 and serum SCCA-IgM could be used for early diagnosis of HCC either each one as a single marker or with AFP complement measurement.

Association between oxidative stress and cord serum lipids in relation to delayed cord clamping in term neonates.

BACKGROUND: Although delayed cord clamping (DCC) is a recent WHO recommendation, early cord clamping (ECC) is still a routine practice in many countries. Limited researches studied the effect of delayed cord clamping on oxidative stress in term neonates; In this study we aim to assess the influence of cord clamping either early or late on oxidative stress in term neonates and to evaluate the association of oxidative stress and cord blood lipids. METHODS: One-hundred mothers and their term neonates were included in the present study. Umbilical cord blood samples were collected from the umbilical vein and umbilical artery immediately following labor. RESULTS: Total cholesterol, total triglycerides and phospholipids levels were significantly higher in the ECC group than the DCC group (p < 0.001 in all). Plasma total antioxidant status was higher in the DCC group than the ECC group (p < 0.001). While, plasma hydroperoxides were lower in the DCC group than the ECC group (p < 0.001). Levels of erythrocytes catalase cytosol, superoxide dismutase and glutathione peroxidase were significantly higher in the DCC group than the ECC group (p < 0.001). CONCLUSION: DCC was associated with a decrease in cord blood lipids and an augmented antioxidant activity. This suggests the protective effect of DCC on the future health of the term neonates and supports the application of DCC in active management of 3rd stage of labor in term neonates.