Lectin-Like OLR1 3'UTR Rs1050286 Gene Polymorphism and Plasma Oxidized-LDL in Coronary Artery Disease and Their Relation to Cardiovascular Risk and Outcomes.

Background: Oxidized low-density lipoprotein (ox-LDL) has an important role in the genesis of coronary atherosclerosis. Lectin-like ox-LDL receptor 1 (OLR1) contributes to the uptake and internalization of ox-LDL. Genetic polymorphisms have been associated with coronary artery disease (CAD). Here we explore the association of plasma levels of ox-LDL and 3' UTR OLR1 (rs1050286) SNP with CAD risk and in-hospital adverse outcomes. Methods: A case-control study enrolled 192 patients with ST-segment elevation myocardial infarction (STEMI), 100 patients with unstable angina, and 100 healthy controls. Baseline, clinical characteristics, and risk scores of the patients were determined. Plasma ox-LDL and other biochemical variables were measured. All subjects are genotyped for OLR1 (rs1050286) by RT-PCR with TaqMan SNP genotyping assay. Results: Plasma ox-LDL was higher with enhanced sensitivity and specificity in identifying patients with STEMI and was found as a significant independent risk factor for CAD in those two groups. Levels of ox-LDL were increased with increasing poor prognostic factors in STEMI patients that are associated with an increased incidence of some adverse events and in-hospital mortality. Elevated STEMI risk was associated with T allele of OLR1 (rs1050286) (odds ratio of 4.9, 95% CI: 2.6-9.4, p< 0.001). STEMI patients who have T allele exhibited higher risk scores, coronary multivessel narrowing, and elevated incidence of in-hospital major adverse clinical events. Conclusion: These results suggest that plasma ox-LDL, as well as T allele of ORL-1 (rs1050286), is associated with the increased risk for developing STEMI and the associated adverse clinical outcomes.

The Prognostic Value of Different Levels of Cortisol and High-Sensitivity C-Reactive Protein in Early Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) ranges in severity from mild to severe with high mortality. Severe AP, similar to other critical illnesses, is associated with changes in cortisol level. Early increase of high-sensitivity C-reactive protein (hs-CRP) as an inflammatory marker could be an indicator of AP progression. We aimed to assess the level of cortisol and hs-CRP on initial diagnosis of AP and identify their prognostic value. METHODS: This case-control study included patients with AP and a control group of healthy subjects. Laboratory tests such as liver profile, kidney functions, blood picture, lactate dehydrogenase, blood glucose, and lipogram were evaluated, the severity of AP was determined, the duration of hospitalization, complications, and outcomes were identified, and the serum levels of cortisol and hs-CRP were assessed. RESULTS: There were 90 patients with AP and 60 controls with a higher percent of females in both groups. Serum cortisol and hs-CRP were significantly higher in AP relative to controls and were higher in severe AP relative to mild AP. Significant positive correlation was present between high cortisol and severity of AP (r = 0.520 and p<0.001) and negatively with pancreatic necrosis (r= - 0.303 and p = 0.007) and morality (r= - 0.432, p = 0.005) while hs-CRP did not show significant correlation. CONCLUSIONS: Different levels of serum cortisol in early AP should be considered on initial diagnosis. High cortisol level was a good prognostic indicator for AP with low mortality. This could have further implications on the appropriate initiation of steroid therapy to prevent necrotizing pancreatitis and lower the mortality. Meanwhile, hs-CRP has a low prognostic value in early AP.

Virulence Characteristics of Biofilm-Forming Acinetobacter baumannii in Clinical Isolates Using a Galleria mellonella Model.

Acinetobacter baumannii is a Gram-negative coccobacillus responsible for severe hospital-acquired infections, particularly in intensive care units (ICUs). The current study was designed to characterize the virulence traits of biofilm-forming carbapenem-resistant A. baumannii causing pneumonia in ICU patients using a Galleria mellonella model. Two hundred and thirty patients with hospital-acquired or ventilator-associated pneumonia were included in our study. Among the total isolates, A. baumannii was the most frequently isolated etiological agent in ICU patients with pneumonia (54/165, 32.7%). All A. baumannii isolates were subjected to antimicrobial susceptibility testing by the Kirby-Bauer disk diffusion method, while the minimum inhibitory concentrations of imipenem and colistin were estimated using the broth microdilution technique. The biofilm formation activity of the isolates was tested using the microtiter plate technique. Biofilm quantification showed that 61.1% (33/54) of the isolates were strong biofilm producers, while 27.7% (15/54) and 11.1% (6/54) showed moderate or weak biofilm production. By studying the prevalence of carbapenemases-encoding genes among isolates, blaOXA-23-like was positive in 88.9% of the isolates (48/54). The BlaNDM gene was found in 27.7% of the isolates (15/54 isolates). BlaOXA-23-like and blaNDM genes coexisted in 25.9% (14/54 isolates). Bap and blaPER-1 genes, the biofilm-associated genes, coexisted in 5.6% (3/54) of the isolates. For in vivo assessment of A. baumannii pathogenicity, a Galleria mellonella survival assay was used. G. mellonella survival was statistically different between moderate and poor biofilm producers (p < 0.0001). The killing effect of the strong biofilm-producing group was significantly higher than that of the moderate and poor biofilm producers (p < 0.0001 for each comparison). These findings highlight the role of biofilm formation as a powerful virulence factor for carbapenem-resistant A. baumannii that causes pneumonia in the ICU.

BCG Vaccine-Induced Trained Immunity and COVID-19: Protective or Bystander?

In late 2019, a new virulent coronavirus (CoV) emerged in Wuhan, China and was named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus spread rapidly, causing the coronavirus disease-2019 (COVID-19) pandemic. Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis (TB) vaccine, associated with induction of non-specific cross-protection against unrelated infections. This protection is a memory-like response in innate immune cells (trained immunity), which is caused by epigenetic reprogramming via histone modification in the regulatory elements of specific genes in monocytes. COVID-19 related epidemiological studies showed an inverse relationship between national BCG vaccination policies and COVID-19 incidence and death, suggesting that BCG may induce trained immunity that could confer some protection against SARS-CoV-2. As this pandemic has put most of Earth's population under quarantine, repurposing of the old, well-characterized BCG may ensure some protection against COVID-19. This review focuses on BCG-related cross-protection and acquisition of trained immunity, as well as the correlation between BCG vaccination and COVID-19 incidence and mortality.

Predictors of Severity and Co-Infection Resistance Profile in COVID-19 Patients: First Report from Upper Egypt.

BACKGROUND: The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide devastating effect with a diagnostic challenge. Identifying risk factors of severity aids in assessment for the need of early hospitalization. We aimed to demonstrate, for the first time, the clinical, laboratory and radiological characteristics of coronavirus disease 2019 (COVID-19) patients, to identify the predictors of severity and to describe the antimicrobial resistance profile in patients from Upper Egypt. MATERIALS AND METHODS: Demographic characters, clinical presentations, laboratory, and radiological data were recorded and analyzed. Presence of other respiratory microorganisms and their sensitivity patterns were identified using the VITEK2 system. Resistance-associated genes were tested by PCR. RESULTS: The study included 260 COVID-19 patients. The majority were males (55.4%) aged between 51 and 70 years. Hypertension, diabetes, and ischemic heart disease were common comorbidities. Main clinical manifestations were fever (63.8%), cough (57.7%), dyspnea (40%) and fatigue (30%). According to severity, 51.5% were moderate, 25.4% mild and 23% severe/critical. Lymphopenia, elevated CRP, ferritin, and D-dimer occurred in all patients with significantly higher value in the severe group. Age >53 years and elevated ferritin ≥484 ng/mL were significant risk factors for severity. About 10.7% of the COVID-19 patients showed bacterial and/or fungal infections. Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus were the predominant isolated bacteria while Candida albicans and Candida glabrata were the predominant isolated fungi. All Staphylococci were methicillin-resistant and carried the mecA gene. Gram-negative isolates were multidrug-resistant and carried different resistance-associated genes, including NDM-1, KPC, TEM, CTX-M, and SHV. CONCLUSION: Older age and elevated serum ferritin were significant risk factors for severe COVID-19. Bacterial co-infection and multidrug resistance among patients with COVID-19 in Upper Egypt is common. Testing for presence of other co-infecting agents should be considered, and prompt treatment should be carried out according to the antimicrobial sensitivity reports.

Impact of the etiology and Vitamin D receptor TaqI rs731236 gene polymorphism on the severity of acute pancreatitis.

BACKGROUND/PURPOSE: This work aimed to assess the impact of different etiologies of acute pancreatitis (AP) and vitamin D receptor (VDR) TaqI rs731236 gene polymorphism on the severity of AP. METHODS: This case-control study included 70 patients with AP and 40 healthy controls. Etiologies of AP were identified by imaging, ANA, cytomegalovirus (CMV) IgM, coxsackie B virus IgM, and IgG4. Genotyping of VDR TaqI rs731236 polymorphism, Laboratory tests and severity scores using Ranson, BISAP, Atlanta and APACHE II scores were determined. RESULTS: The age in AP patients was 36.03 ± 10.76, and females were 85.7%. The etiologies of AP were as follows: biliary (51.4%), coxsackievirus (22.9%), autoimmune (14.3%), post-ERCP (8.6%) and 2.9% were idiopathic. The TT genotype of VDR polymorphism was significantly more common in AP than control (P = .001) and allele T dominated in AP group (OR = 2; 95% CI: 0.665-5.64). Most cases showed low severity scores with significant differences among etiologies and VDR genotypes. Biliary pancreatitis showed highest percentages of severe AP. However, etiologies and VDR polymorphism were not predictors of severity. CONCLUSION: Etiology of AP could have impact on the disease severity. VDR gene polymorphism increases the risk of AP. Neither the etiology nor VDR gene polymorphism could predict AP severity.

Emergence of Cronobacter sakazakii in Cases of Neonatal Sepsis in Upper Egypt: First Report in North Africa.

BACKGROUND AND AIM: Cronobacter sakazakii (C. sakazakii) has attracted considerable attention as an emerging neonatal pathogen and has been associated with outbreaks of life-threatening septicemia, necrotizing enterocolitis, and meningitis in neonates and infants globally. No data about the role of C. sakazakii as a cause of neonatal sepsis in North Africa is availale. Herein, we aimed to study the incidence of C. sakazakii in cases of neonatal sepsis, its distribution in different food samples in Egypt, antimicrobial profile, and the ability of the strains to form biofilms. METHODS: A total of 100 positive blood cultures from cases of neonatal sepsis admitted to the neonatal ICU at Assiut University Children's Hospital, Egypt, were analyzed. In addition, 1,100 food samples, including 400 powdered infant formula (PIF), 500 herbs, and 200 water samples were screened for the presence of C. sakazakii. We evaluated the antimicrobial profile and the ability of the strains to form biofilms. RESULTS: Cronobacter sakazakii was detected in 12 out of 100 cases of neonatal sepsis. The organism was also isolated from PIF, herbs, and water in percentages of 17.5, 9.2, and 7.5%, respectively. Regarding the antimicrobial sensitivity, all strains were resistant to ampicillin, amoxicillin, ampicillin/sulbactam, clindamycin, cephalothin, and cephalexin. In addition, C. sakazakii strains showed the ability to form biofilms, but with variable degrees of cell density. CONCLUSION: We reported, for the first time, cases of neonatal sepsis caused by the emerging life-threatening pathogen C. sakazakii in Egypt. The organism was also detected in contaminated PIF, herbs, and water, which may be sources of infection for neonates, especially in countries where natural herbs are widely used as an alternative medicine. Finally, collective efforts by the parents, manufacturers of PIF, and healthcare personnel are essential to prevent serious infections caused by C. sakazakii, particularly in infants.

Circulating miRNA-21 and miRNA-23a Expression Signature as Potential Biomarkers for Early Detection of Non-Small-Cell Lung Cancer.

BACKGROUND AND AIM: Lung Cancer (LC) is a major cancer killer worldwide, and 5-yr survival is extremely poor (≤15%), accentuating the need for more effective diagnostic and therapeutic strategies. Studies have shown cell-free microRNAs (miRNAs) circulating in the serum and plasma with specific expression in cancer, indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy. This study aimed to identify differentially-expressed two miRNAs in the plasma of Non-Small Cell Lung Cancer (NSCLC) patients that might be a clinically useful tool for lung cancer early detection. miRNA-21 is one of the most abundant oncomirs. miRNA-23a functions as an oncogene in several human cancers, however, its clinical value has not been investigated in NSCLC. MATERIALS AND METHODS: A case-control study was conducted in Assiut University Hospital, Egypt, from 2017 to 2018. Plasma samples were obtained from 45 NSCLC patients. The expression level of miR-21 and miRNA-23a was detected by qRT-PCR and compared to 40 healthy control subjects. The relation between both miRNAs and clinicopathological parameters was evaluated. RESULTS: The expression level of miR-21 and miRNA-23a was significantly up-regulated (36.9 ± 18.7 vs. 1.12 ± 0.84 and 24.7 ± 19.09 vs. 1.16 ± 0.45) in NSCLC compared to matched controls (P<0.0001each). There was a significant difference in the level of plasma miRNA-21 and miRNA- 23a expression between the different grades of the disease (P = 0.032 and P = 0.001, respectively). The plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with distant metastasis (n = 20) were significantly higher than those in the patients without metastasis (n = 25) (P<0.0001 each), the expression of miR-21 and miRNA-23a was significantly associated with tumor size (P = 0.001, P = 0.0001, respectively), but not significantly related to lymph node metastasis (P = 0.687 and 0.696, respectively). A positive correlation was observed between miRNA-21 and miRNA-23a (r = 0.784, P<0.01), There was no significant difference in the plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with different histopathological types. CONCLUSION: miR-21 and miR-23a might play an oncogenic role in LC and is a poor prognostic factor. Switching off miRNA-21 and miRNA-23a may improve the treatment of LC. Our results must be verified by large-scale prospective studies with standardized methodology.

Association of Treg and TH17 Cytokines with HCV Pathogenesis and Liver Pathology.

Chronic hepatitis C (CHC) infection is considered a high risk for development of end-stage liver diseases, particularly server hepatitis, decompensated liver cirrhosis, and hepatocellular carcinoma. Regulatory T cells (Treg) and T-helper 17 (TH17) associated cytokines presumed to play a pivotal role in the immune pathogenesis of HCV infection and stimulate autoimmune diseases. Herein, we tried to assess the association of Treg and TH 17 cytokines with HCV pathogenesis and liver pathology. Fifty CHC infected patients and twenty HCV free controls were included in this study, IL17, IL21, IL10, IL4, TGF- and IL35 serum levels were assessed in both groups using enzyme linked immunosorbent assay (ELISA). CHC infected patients had statistically significant higher values of all serum cytokine levels when compared to the control group (P < 0.0001) for each. Additionally, serum levels of IL17, IL10 and IL35 were positively correlated with viral load. Also, the serum level of IL17 IL21, IL10 and IL35 was positively correlated with ALT serum levels. Only IL21 and IL10 were positively correlated with AST levels. Serum IL17, IL10, TGF- and IL35 levels were significantly elevated in CHC patients with advanced fibrosis stages. We concluded that CHC infected patients displayed high serum levels of Treg and TH17 associated cytokines. Collectively, these results support the hypothesis that liver damage in CHC infection might be due to an immune-mediated destructive mechanism rather than to the direct cytopathic effect of the virus itself.