FURIN, IFNL4, and TLR2 gene polymorphisms in relation to COVID-19 severity: a case-control study in Egyptian patients.

BACKGROUND AND AIM: A wide range of clinical manifestations and outcomes, including liver injury, have been reported in COVID-19 patients. We investigated the association of three substantial gene polymorphisms (FURIN, IFNL4, and TLR2) with COVID-19 disease susceptibility and severity to help predict prognosis. METHODS: 150 adult COVID-19-assured cases were categorized as follows: 78 patients with a non-severe presentation, 39 patients with severe disease, and 33 critically ill patients. In addition, 74 healthy controls were included. Clinical and laboratory evaluations were carried out, including complete and differential blood counts, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin, ferritin, interleukin-6 (Il-6), and liver and kidney functions. FURIN (rs6226), IFNL4 (rs12979860), and TLR2 (rs3804099) genotyping allelic discrimination assays were conducted using real-time PCR. RESULTS: The FURIN, IFNL4, and TLR2 genotypes and their alleles differed significantly between COVID-19 patients and controls, as well as between patients with severe or critical illness and those with a non-severe presentation. According to a multivariable regression analysis, FURIN (C/T + T/T) and TLR2 (T/C + C/C) mutants were associated with COVID-19 susceptibility, with odds ratios of 3.293 and 2.839, respectively. FURIN C/C and IFNL4 T/T mutants were significantly linked to severe and critical illnesses. Multivariate regression analysis showed that FURIN (G/C + C/C) genotypes and IFNL4 T/T homozygosity were independent risk factors associated with increased mortality. CONCLUSION: FURIN, IFNL4, and TLR2 gene variants are associated with the risk of COVID-19 occurrence as well as increased severity and poor outcomes in Egyptian patients.

Unraveling the controversy between fasting and nonfasting lipid testing in a normal population: a systematic review and meta-analysis of 244,665 participants.

BACKGROUND: The final decision to fast or not fast for routine lipid profile examination in a standard, healthy population is unclear. Whereas the United States and European protocols state that fasting for regular lipid analysis is unnecessary, the North American and Chinese guidelines still recommend fasting before routine lipid testing. AIM: This study aimed to unravel the contradiction between the different protocols of lipid profile testing worldwide and clarify the effect of diet on lipid profile testing only in a regular, healthy population. METHODS: A literature search was conducted through May 2024. The analyses included studies performed from the date 2000 until now because the contradiction of guidelines for lipid profile testing appeared for the first time in this period. A planned internal validity evaluation was performed using the National Institute of Health (NIH) quality measurement tools for observational cohort, case‒control, controlled interventional, and cross-sectional studies. The data were synthesized according to RevMan 5.3. RESULTS: Eight studies with a total of 244,665 participants were included. The standardized mean difference in cholesterol in six studies showed significant differences in overall effect among fasting and nonfasting states (P < 0.00001), as did high-density lipoprotein cholesterol (P < 0.00001). At the same time, with respect to triglycerides and low-density lipoprotein cholesterol, there were notable variations in the overall effect between the fasted and nonfasted states (P < 0.00001 and P ≤ 0.001, respectively). CONCLUSIONS: This meta-analysis concluded that fasting for lipid profile testing is preferred as a conservative model to reduce variability and increase consistency in patients' metabolic status when sampling for lipid testing.

Leptin gene Polymorphism and Leptin protein levels in Pediatric Autoimmune Hepatitis.

BACKGROUND: Leptin plays a role in regulating energy balance, immunity, and inflammation. Studies suggest higher leptin levels might be associated with various autoimmune diseases. Most of them were in adult. To our knowledge, our study is one of the few that describe serum leptin level and leptin gene polymorphism in children with autoimmune hepatitis (AIH). OBJECTIVE: Our study aims to explore the association between serum leptin level and genetic variations in leptin gene with the likelihood of AIH in children. PATIENTS AND METHODS: Thirty-one children with AIH and 29 healthy children serving as a control group were included. Serum leptin levels were measured by ELISA assays. Leptin rs2167270 genotyping was done using the real time-PCR. The relationship of serum leptin level and leptin gene polymorphism with patients' data was studied. Patients follow up to assess treatment response. RESULTS: Children with AIH had significantly higher levels of leptin compared to healthy controls. GG genotype was significantly more prevalent in the AIH group compared to controls. CONCLUSION: High serum leptin levels and leptin gene polymorphism may play a role in AIH development. It is worthy to recognize if leptin can serve as diagnostic and/or therapeutic target in AIH in children.

Sofosbuvir (+) daclatasvir (+) ribavirin in Egyptian patients with hepatitis C virus: Therapeutic outcomes and the prognostic role of natural killer cells.

BACKGROUND: One of the prominent causes of chronic liver disease worldwide is the hepatitis C virus (HCV). HCV believed that innate immunity contributes to a sustained virological response (SVR) to the treatment of Sofosbuvir (SOF) (+) Daclatasvir (DCV) (+) Ribavirin (RBV). This study aimed to evaluate the impact of SOF (+) DCV (+) RBV therapy and persistent HCV infection on the subset of natural killer cells (NK) in HCV genotype four patients from Egypt. MATERIALS AND METHODS: One hundred and ten patients with persistent HCV infections requiring SOF (+) DCV (+) RBV therapy were grouped, and a flow cytometry (FCM) study of the NK cell subset in peripheral blood was performed. The assessment was performed before and after three and/or six months of the cessation of viral suppression therapy when a patient had a long-term viral response (SVR). One hundred and ten volunteers from the National Liver Institute's (NLI) blood bank were selected as controls. RESULTS: Patients with chronic HCV infection before therapy had considerably lower CD16+ and CD3- CD56+ cells than controls. Their levels increase during SOF (+) DCV (+) RBV therapy. In patients with SVR during treatment, CD16+ and CD3- CD56+ cells increased significantly compared to those who did not get SVR. Furthermore, CD56+ cells were significantly higher in patients with persistent infection before treatment than controls but diminished with the response to treatment. CONCLUSION: NK cell activation following SOF (+) DCV (+) RBV therapy and polarization to cytotoxicity occurred early in HCV antiviral therapy and was elevated in the respondents. Our data illustrated that establishing an inhibitory cytotoxic NK profile is related to therapeutic outcomes.

A pilot study on the relation between irisin single-nucleotide polymorphism and risk of myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is the major cause of death and disability worldwide. Many recent studies revealed the relationship between circulating irisin levels, endothelial dysfunctions and subclinical atherosclerosis in adult patients. OBJECTIVES: The aim of this study was to investigate the distribution of Irisin gene single nucleotide polymorphism in patients with MI and its association with other clinical and laboratory variables in these patients. PATIENTS AND METHODS: This study was carried out in 100 patients with MI, and 100 healthy subjects served as controls. All studied subjects underwent laboratory investigations, including measurement of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c) high-density lipoprotein cholesterol (HDL-c), creatinine kinase-MB (CK-MB), troponin I (TnI) and genotyping of rs 3480 and rs726344 of Irisin genes using the TaqMan Allelic Discrimination assay technique. RESULTS: There was a significant difference of Irisin genotypes in patients when compared to controls. By estimating odd ratio (OR) an association was found between G allele of rs 3480 and A allele of rs726344with increase the risk of developing myocardial infarction by 4.03 and 3.47 fold respectively. GG of rs 3480 carriers had significantly increased Troponin I and triglyceride levels, while GA carriers of rs726344 had significantly increased CKMB, Total cholesterol, LDLc, HDLc, troponin I and triglyceride levels compared with other genotypes. CONCLUSION: G allele of rs 3480 and A allele of rs726344can considered as genetic risk factors for MI; these findings could have an impact on preventive strategy for myocardial infarction.

COVID-19 outbreak in Jordan: Epidemiological features, clinical characteristics, and laboratory findings.

BACKGROUND: In March 2020, an outbreak of coronavirus 19 (COVID-19) was detected in the North of Jordan. This retrospective study is the first from Jordan to report the epidemiologic, clinical, laboratory, and radiologic characteristics of COVID-19 infected patients. METHODS: All patients with laboratory-confirmed COVID-19 infection by RT-PCR in the North of Jordan admitted between March 15 and April 2, 2020 were included. The clinical features, radiological, and laboratory findings were reviewed. RESULTS: Of 81 patients affected, 79 (97.5%) shared a common exposure to four recent travelers from endemic areas. The mean age was 40 years. Although about half (44 [54.3%]) were females, symptomatic patients were mostly females (75%). The most common presenting symptoms were nasal congestion, sore throat and dry cough. Less than one-third (31%) had chronic diseases. Although 84% of patients reported receiving Bacille Calmette-Guérin (BCG) vaccination, more asymptomatic patients had BCG than symptomatic (p = 0.017). Almost all patients (97.5%) had an elevated D-dimer level. Erythrocyte sedimentation rate (ESR) and c-reactive protein were elevated in 50% and 42.7% of patients, respectively. High ESR found to be the predictor of abnormal chest radiograph observed in 13 (16%) patients with OR of 14.26 (95% CI 1.37-147.97, p = 0.026). CONCLUSIONS: An outbreak of COVID-19 infection in northern Jordan affected more females and relatively young individuals and caused mainly mild illnesses. The strict outbreak response measures applied at early stages probably contributed to the lenient nature of this outbreak, but the contribution of other factors to such variability in COVID-19 presentation is yet to be explained.

Crossover Evaluation of Compressors and Nebulizers Typically Used by Cystic Fibrosis Patients.

BACKGROUND: Compressor/nebulizer units are used to deliver inhaled medications to patients with cystic fibrosis. Practitioners and parents frequently replace either the compressor or the nebulizer with a similar component from a different brand. We hypothesized that these changes could affect the compressor/nebulizer flow-pressure and aerosol characteristics. METHODS: The following compressors were studied: Pari Vios, Pulmo-Aide model 5650D, and Inspiration Elite model HS456. The following nebulizers were studied: Pari LC Plus, Viox, and SideStream Plus. Units that underwent intense use were tested. The recommended compressor/nebulizer combinations by the manufacturers were compared to all other combinations. In-line measurements of maximal flow and pressure were done for all combinations. A Next Generation Impactor was used to determine particle-size characteristics of albuterol (2.5 mg/3 mL). A breathing simulator programmed to deliver an adult breathing pattern was used. Albuterol concentration was measured with spectrophotometry at 276 nm. The following variables were studied: maximal flow and pressure generated by the compressor/nebulizer, mass median aerodynamic diameter, percentage of drug mass contained in particles < 5 µm, and inhaled mass in the respirable range. RESULTS: Replacing the nebulizer resulted in changes in the flow-pressure characteristics, particle size, and inhaled mass in the respirable range of the paired compressor/nebulizers. The changes were more pronounced when the nebulizer was replaced than when the compressor was changed. CONCLUSIONS: Our findings indicate that, in general, replacing the nebulizer or compressor with a different brand changes the flow-pressure and aerosol characteristics. Practitioners should be cautious when changing compressor/nebulizer pairs unless they are aware of the resulting impact on the flow-pressure and aerosol characteristics.