L-carnitine decreases myocardial injury in children undergoing open-heart surgery: A randomized controlled trial.

Myocardial injury in open-heart surgery is related to several factors including ischemia-reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\kg\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group.   Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.   Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients. What is Known: • Myocardial injury in open-heart surgery is related to several factors including ischemia-reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. • L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery. What is New: • L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group. • L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.

Acute lymphoblastic leukemia in children and SALL4 and BMI-1 gene expression.

BACKGROUND: Sal-like protein 4 transcription factor (SALL4) and B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) gene were reported to cause treatment failure and relapse in several malignancies. We aimed to evaluate the prognostic value of SALL4 and BMI-1 in children with acute lymphoblastic leukemia (ALL). METHODS: This prospective cohort study was carried out on 60 children with ALL as the patient group and 60 age- and sex-matched children as the control group. We evaluated the expression pattern of both SALL4 and BMI-1 genes in the peripheral blood using real-time reverse transcriptase-polymerase chain reaction in children with ALL at initial diagnosis before chemotherapy. We followed up with the patient group for 2 years for relapse or death. RESULTS: Both SALL4 and BMI-1 were overexpressed in ALL children compared to the control group. Moreover, the expression of SALL4 and BMI-1 in patients with relapse was significantly higher than those with complete remission. The best cut-off of SALL4 and BMI-1 to predict relapse were >2.21 and 0.55 yielding sensitivity of 92.3% and 84.6%, respectively. Patients with overexpression of SALL4 and BMI-1 had significantly shorter overall and disease-free survival. CONCLUSIONS: SALL4 and BMI-1 could be useful prognostic markers in children with ALL to predict relapse.

lncRNA GAS5 and RUNX1 Genes in Children With Primary Immune Thrombocytopenia.

We aimed to evaluate the expression levels and the prognostic value of growth arrest specific 5 (GAS5) and runt-related transcription factor 1 (RUNX1) genes in children with ITP. This prospective cohort study included 100 patients with newly diagnosed ITP (patient group) and 100 healthy children of matched age and sex (control group). We evaluated the expression levels of both GAS5 and RUNX1 genes at the time of diagnosis before the introduction of treatment. GAS5 was under-expressed, while RUNX1 was over-expressed among the newly diagnosed ITP children compared with the control group. Patients with GAS5 levels >0.50 had a significantly faster recovery compared with patients with levels≤0.50 while patients with levels of RUNX1≤2.6 had a significantly faster recovery compared with patients with levels >2.6. The best cut-off values of GAS5 and RUNX1 to predict complete recovery of ITP were ˃0.40 and ˂3.18, respectively, yielding a sensitivity of 76.47% and 79.41%, respectively. The best cut-off values of GAS5 and RUNX1 expression that predict chronic ITP were ˂0.17 and ˃4.1, respectively, yielding sensitivity of 88.89% and 77.78%, respectively. GAS5 and RUNX1 could be useful markers in children with primary ITP to predict disease course.

Vitamin D and nonalcoholic fatty liver disease in children: a randomized controlled clinical trial.

Vitamin D is reported to have anti-inflammatory and insulin-sensitizing effects, yet vitamin D effects on hepatic fat content in children with nonalcoholic fatty liver disease (NAFLD) are not studied sufficiently. We aimed to evaluate the role of vitamin D supplementation on the hepatic fat content and NAFLD progression in children. This randomized controlled clinical trial was performed on 109 children with biopsy-proven NAFLD; only 100 patients completed the study. Patients were randomly assigned into two groups: the treatment group who received 2000 IU/day vitamin D for 6 months and the control group who received a placebo. Anthropometric measurements, vitamin D levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), serum triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting blood glucose (FBG), fasting blood insulin level (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), and serum calcium level were measured at the beginning and the end of the study. Liver biopsy was taken before and at the end of the study for all included children. There was a significant improvement of the hepatic steatosis and lobular inflammation by liver biopsy in the treatment group after treatment. However, there was no significant effect on the hepatocyte ballooning or hepatic fibrosis. There were significant decrease of AST, ALT, TG, LDL, FBG, FBI, and HOMA-IR and significant increase of vitamin D levels and HDL in the treatment group compared to the placebo group (P < 0.05).Conclusion: Vitamin D supplementation was found to be beneficial in the treatment of NAFLD in children.Trial registration: www.pactr.org , PACTR201710002634203. What is Known: • Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in pediatrics. • Several studies reported a negative association between low serum vitamin D level and grades of NAFLD. What is New: • Vitamin D supplementation has significantly decreased hepatic steatosis and lobular inflammation and improved the grades of NAFLD in children, confirmed by liver biopsy, but no effect on hepatocyte ballooning or fibrosis was observed. • Adjuvant vitamin D supplementation is recommended in children with NAFLD.

Predictive Value of Plasma Copeptin Level in Children with Acute Heart Failure.

We investigated the ability of copeptin level to predict adverse outcome in pediatric heart failure (HF) and correlated copeptin level with various clinical and echocardiographic data. This cohort study was carried out on forty children with clinical picture of acute HF as the patient group and forty healthy children of matched age and sex as the control group. Echocardiographic examination and plasma copeptin level were performed for all included children at admission. Patients were followed up for 6 months for mortality or readmission. Plasma copeptin level was significantly higher in the patient group (16.2 ± 5) pmol/L compared to the control group (4.1 ± 2.3) pmol/L, P ˂0.001. Moreover, copeptin level was positively correlated with Ross classification, being the highest in patients with class IV (19.6 ± 3.9) pmol/L compared to those with class III (15.2 ± 4) pmol/L and class II (10.4 ± 1.5) pmol/L. Copeptin levels were significantly higher in patients with bad prognosis (21.2 ± 4.1) pmol/L compared to those with good prognosis (14.5 ± 4.1) pmol/L, P ˂0.001. Copeptin level had a significant positive correlation with age, heart rate, respiratory rate, and ROSS classification. On the contrary, copeptin level had a significant negative correlation with left ventricular fraction shortening and diastolic function. Copeptin at cut-off value of ≥ 19.5 pmol/L yielded a sensitivity of 75% and a specificity of 93% to predict adverse outcome in children with HF. Plasma copeptin level has a good prognostic value to predict adverse outcome in pediatric heart failure. Moreover, copeptin correlate well with the severity of pediatric HF.

The Expression of Circulating miR-497 and Metadherin in Hepatocellular Carcinoma: Relation to the Tumor Characteristics and Patients' Survival.

Objectives: This study aimed to evaluate the prognostic significance and relationship of miR-497 and metadherin to hepatocellular carcinoma (HCC) tumor characteristics and patients' survival. Methods: This study enrolled 120 (60 HCC patients and 60 healthy) subjects. Serum miR-497 and metadherin mRNA relative expression were analyzed by real-time quantitative reverse transcription polymerase chain reaction. The overall survival (OS) of HCC patients was assessed using the Kaplan-Meier curve and log-rank test. Results: Serum miR-497 showed statistically significant downregulation in HCC patients compared to controls (p < 0.001). Serum metadherin mRNA relative expression was significantly upregulated in HCC patients compared to controls (p < 0.001). Both serum miR-497 and metadherin mRNA expression were significantly associated with the number of tumor foci (p = 0.028 and 0.001, respectively), tumor size (p = 0.022 and <0.001, respectively), nodal metastasis (p = 0.003 and 0.003, respectively), distant metastasis (p = 0.003 and 0.003, respectively), vascular invasion (p = 0.040 and <0.001, respectively), and BCLC staging (p = 0.043 and 0.004, respectively). The overall survival was lower in patients with low miR-497 expression (p = 0.046) and in patients with high metadherin expression (p < 0.001). Conclusions: The expression levels of miR-497 showed downregulation in HCC patients, but metadherin expression showed upregulation. Both markers were inversely related and closely correlated with tumor characteristics and patients' survival.

The Prognostic Significance of MACC1 Expression in Breast Cancer and Its Relationship to Immune Cells in the Tumor Microenvironment and Patient Survival.

Breast cancer (BC) is one of the most prevalent malignancies among females worldwide. Globally, distant metastases were reported to be responsible for a large proportion of breast cancer-related deaths. The metastasis-associated colon cancer-1 (MACC1) gene was reported as a reliable biomarker for early detection of metastasis and prediction of prognosis of breast cancer. This study investigated the prognostic significance of MACC1 in breast cancer in relation to the clinicopathologic characteristics and patients' survival. Furthermore, the possible correlation between MACC1 expression and the different immune cells in the tumor microenvironment was explored. MACC1 mRNA was identified using quantitative reverse transcription polymerase chain reaction in 120 breast cancer specimens and adjacent non-cancerous tissues. MACC1 mRNA expression was significantly higher in the cancerous relative to the non-cancerous tissues (p < 0.001). High MACC1 expression was significantly associated with poor prognostic parameters, such as larger tumor size, grade III tumors, positive nodal metastasis, lymphovascular invasion, stage III tumors, and elevated Ki-67 expression. Higher MACC1 mRNA levels were positively correlated with CD163+ tumor-associated macrophages (r = 0.614, p < 0.001), and were negatively correlated with CD56+ natural killer cells (r = -0.398, p < 0.001) and CD8+ cytotoxic T lymphocytes (r = -0.323, p < 0.001). MACC1 expression was associated with poor patient overall survival (OS) and progression-free survival (PFS) (p < 0.001). Multivariate analysis suggested that MACC1 expression and the presence of lymphovascular invasion could be independent prognostic indicators for breast cancer (p = 0.015 and 0.042, respectively). In conclusion, MACC1 is highly expressed in cancerous tissues and is significantly related to poor prognostic factors, overall survival, and progression-free survival. MACC1 may influence infiltration of the immune cells in the tumor microenvironment, enhance immune escape of tumor cells, and may serve as a reliable independent prognostic factor for breast cancer.

Helicobacter pylori infection and gut microbiota in adolescents: Is there a relation?

Helicobacter pylori infection is a prevalent global infection associated with several complications such as peptic ulcer, upper gastrointestinal bleeding, and stomach cancer. An imbalance in the gut microbiota composition or the relationship between the microbiota and the host may be implicated in the infection. To investigate this, we studied the intestinal microbiota of 50 newly infected adolescents with H. pylori compared with 50 age-matched and sex-matched healthy controls. The gut microbiota composition was assessed using real-time polymerase chain reaction (RT-PCR), and the fecal bacterial diversity and composition were compared between groups. Our findings revealed that Clostridium difficile and Salmonella spp. were significantly higher in the patient group compared to the control group. Additionally, lower counts of eubacteria, Bacteroides fragilis, Lactobacillus spp., Escherichia coli, and Methanobrevibacter smithii, were observed in the gut of adolescents with H. pylori. Conversely, adolescents with H. pylori infection had non-significantly higher counts of Bifidobacterium spp., C. difficile, and Salmonella spp. Multiple logistic regression analysis revealed that a greater abundance of Bifidobacterium spp. and Salmonella spp., a higher prevalence of C. difficile, and a lower abundance of Lactobacillus spp. were predictive of H. pylori infection. Overall, our results suggest that H. pylori infection is associated with changes in fecal microbiome composition.

Parasitic infections as potential risk factors for attention deficit hyperactivity disorder (ADHD) in children.

Attention deficit hyperactivity disorder (ADHD) represents a mysterious neuropsychiatric alarming concern due to indefinite etiopathogenesis among children. Notably, the studies which investigated the correlation between ADHD and parasitic infections are insufficient. Therefore, this research aimed to assess the correlation between ADHD and some tissue dwelling and intestinal parasitic infections in children. The study was conducted on 200 children, including 100 children suffering from ADHD (Group I) and 100 healthy children as a control group (Group II). All caregivers fulfilled predesigned sociodemographic form and Conners parent rating scale (CPRS-48) questionnaire. Blood samples were collected to determine hemoglobin level as well as relative eosinophilic count. The presence of anti-Toxoplasma IgG and anti-Toxocara IgG in serum by Enzyme-Linked Immunosorbent Assay (ELISA) was further investigated. Also, micronutrients as zinc, iron, and copper levels were measured. Schistosoma antigen was investigated in urine samples. Stool samples were subjected to direct wet smear, concentration technique and modified Ziehl-Neelsen (MZN) staining for coccidian parasites detection. Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica antigens were investigated in stool samples. Group I expressed more liability to sociodemographic risk factors, decreased levels of Hb, iron, zinc, and copper with statistically significant difference (P < 0.001). Comparison between Group I and Group II regarding the detected parasitic infections exhibited statistically significant difference except Schistosoma antigen positivity which expressed no statistical significance. The present study concluded that the parasitic infections with their consequences are potential risk factors in children with ADHD indicating that their early diagnosis and treatment may help in ADHD prevention.

A Simple Scoring Model Predicting the Outcome of COVID-19 Patients: Tanta COVID Score.

BACKGROUND: COVID-19 is a worldwide pandemic with high rates of morbidity and mortality, and an uncertain prognosis leading to an increased risk of infection in health providers and limited hospital care capacities. In this study, we have proposed a predictive, interpretable prognosis scoring system with the use of readily obtained clinical, radiological and laboratory characteristics to accurately predict worsening of the condition and overall survival of patients with COVID-19. METHODS: This is a single-center, observational, prospective, cohort study. A total of 347 patients infected with COVID-19 presenting to the Tanta University Hospital, Egypt, were enrolled in the study, and clinical, radiological and laboratory data were analyzed. Top-ranked variables were identified and selected to be integrated into a Cox regression model, building the scoring system for accurate prediction of the prognosis of patients with COVID-19. RESULTS: The six variables that were finally selected in the scoring system were lymphopenia, serum CRP, ferritin, D-Dimer, radiological CT lung findings and associated chronic debilitating disease. The scoring system discriminated risk groups with either mild disease or severe illness characterized by respiratory distress (and also those with hypoxia and in need for oxygen therapy or mechanical ventilation) or death. The area under the curve to estimate the discrimination performance of the scoring system was more than 90%. CONCLUSION: We proposed a simple and clinically useful predictive scoring model for COVID- 19 patients. However, additional independent validation will be required before the scoring model can be used commonly.

Immunoprotective inference of experimental chronic Trichinella spiralis infection on house dust mites induced allergic airway remodeling.

Allergic bronchial asthma is characterized by chronic inflammation of the respiratory airways mediated by T-helper 2 (Th2), Th17 and their cytokines. Although most asthmatic patients suffer from allergic airway remodeling (AAR), aggressive anti-allergic treatment failed to reverse it. The hygiene hypothesis illuminated the counter relationship between allergy and helminthic infections. The immune system is modulated by Trichinella spiralis (T. spiralis) infection to maintain homeostasis. Therefore, this work aimed to investigate the impact of chronic T. spiralis infection on induced AAR in C57BL/6 mice sensitized by house dust mites (HDM) allergens. Forty mice were divided into 3 groups: I (10 healthy mice), IΙ (15 HDM sensitized mice), and ΙΙI (15 T. spiralis chronically infected mice and sensitized with HDM allergens). The assessment aimed to evaluate the effects of regulatory CD4+CD25+FOXP3+ cells (Tregs) and their cytokines comparative to hypersensitivity mediated cytokines. Chronic T. spiralis infection effectively prevented the host's AAR. This result was evidenced by upregulated Tregs in blood by flow cytometric analysis and increased interleukin-10 (IL-10) levels in bronchoalveolar lavage (BAL) by Enzyme linked immunosorbent assay (ELISA) as well as improved lung histopathological changes. Also, serum HDM specific immunoglobulin E (IgE), BAL eosinophils, BAL IL-5 levels, and IL-17 gene expression in lung tissues were significantly reduced in T. spiralis chronically infected mice. In conclusion, the immune response in chronic T. spiralis infection could provide a promising mechanistic tool for protection against AAR, which paves the way for innovative preventive measures of other immunological disorders.

Galectin-3 as a prognostic biomarker for diabetic nephropathy.

INTRODUCTION: Diabetic nephropathy (DN) represents one of the main causes of end-stage renal disease in type 2 diabetes mellitus (DM) patients. Galectin-3 has been implicated in pathogenesis of many pathological conditions. To date, there are limited data regarding the relationship between galectin-3 and DN. AIM OF THE STUDY: Evaluation of serum galectin-3 as a novel prognostic biomarker in patients with DN. PATIENTS AND METHODS: This prospective study was carried out in the Internal Medicine and Clinical Pathology Departments, Tanta University Hospital, Egypt, from March 2015 to March 2018 on 300 patients with type 2 DM. Patients were divided into three groups: group I included 100 patients with albumin/creatinine ratio (ACR) <30 mg/g (normoalbuminuria), group II included 100 patients with ACR within 30-300 mg/g (microalbuminuria), and group III included 100 patients with ACR >300 mg/g (macroalbuminuria). All patients were subjected to the following: full history taking, clinical examination, and laboratory evaluation (HbA1c, creatinine, estimated glomerular filtration rate, ACR, and serum galectin-3). RESULTS: The mean levels of galectin-3 were significantly higher in patients with macroalbuminuria than in those with microalbuminuria and normoalbuminuria. Galectin-3 was a significant predictor for progression to microalbuminuria, macroalbuminuria, dialysis, and death among patients with type 2 DM. CONCLUSION: Based on this single center prospective study, serum galectin-3 is considered a significant predictor for DN progression among patients with type 2 DM.