Impact of Toll-Like Receptor 2 and 9 Gene Polymorphisms on COVID-19: Susceptibility, Severity, and Thrombosis.

Background: Toll-like receptors (TLRs) play an important role in activation of innate and adaptive immune responses. Aim: We aimed to detect the association between TLR2 rs5743708 G>A and TLR9 rs5743836 C>T variants and COVID-19 disease susceptibility, severity, and thrombosis by using neutrophil extracellular traps (NETs). Subjects and Methods: We included 100 adult COVID-19 patients as well as 100 age- and gender-matched normal controls. Participants were genotyped for TLR2 rs5743708 and TLR9 rs5743836. Citrullinated Histone (H3) was detected as an indicator of NETs. Results: The mutant (G/A and C/C) genotypes and (A and C) alleles of TLR2 rs5743708 and TLR9 rs5743836, respectively, have been significantly related to a higher risk of COVID-19 infection, representing a significant risk factor for the severity of COVID-19. There was no significant association between the two variants and citrullinated histone (H3). Conclusion: TLR2 rs5743708 and TLR9 rs5743836 variants have been significantly related to a higher risk and severity of COVID-19 infection but had no effect on thrombus formation.

Clinical and Prognostic Significance of Baseline Serum Vitamin D Levels in Hospitalized Egyptian Covid-19 Patients.

Background and Aim: Vitamin D is a hormone with essential roles in both cellular metabolism and immunity. It controls calcium homeostasis and modulates innate and adaptive immune system responses. Many studies suggested an association between vitamin D deficiency and clinical outcomes of covid-19 infection, while others failed to document such a relation. The present study aimed to evaluate the clinical and prognostic significance of baseline vitamin D levels in hospitalized Egyptian covid-19 patients. Patients and Methods: The present retrospective study included 300 hospitalized covid-19 patients. Patients were submitted to standard clinical, laboratory, and radiological assessment. According to vitamin D levels, patients were classified to have normal levels (≥30), insufficient levels (20-29) or deficient levels (<20). Results: According to their vitamin D levels, patients were classified into those with normal vitamin D (n=135), others with vitamin D insufficiency (n=114), and a third group with vitamin D deficiency (n=51). Patients with normal vitamin D levels and vitamin D insufficiency are significantly younger [median (IQR): 49.0 (39.0-57.0) versus 51.0 (40.0-61.0) and 55.0 (43.0-62.0) years, respectively, p=0.012] and had less frequency of severe disease (24.4% versus 40.4% and 51.0%, respectively) when compared with those with vitamin D deficiency. Moreover, they had significantly lower levels of D dimer [median (IQR): 1.5 (0.9-2.5) versus 1.8 (0.9-3.1) and 2.0 (1.0-3.2)], CRP [median (IQR): 58.0 (30.0-120.0) versus 76.0 (42.5-160.0) and 105.0 (74.0-208.0), respectively, p<0.001], ferritin [median (IQR): 458.0 (240.0-759.0) versus 606.0 (433.8-897.8) and 820.0 (552.0-1087.0), respectively, p<0.001], and procalcitonin [median (IQR): 290.0 (152.0-394.0) versus 372.5 (227.0-530.5) and 443.0 (272.0-575.0), respectively, p<0.001]. Only lower vitamin D levels were significant predictors of mortality in multivariate analysis [OR (95% CI): 0.88 (0.84-0.92), p<0.001]. Conclusion: Low vitamin D levels are related to exaggerated inflammatory response, disease severity, and poor clinical outcome in hospitalized covid-19 patients.

Median Nerve Affection in Hypertensive Patients with and without Diabetes High-Resolution Ultrasound Assessment.

PURPOSE: Diabetes is a documented risk factor for peripheral neuropathy. It was reported that associated hypertension could increase this risk. The present study aimed to assess the effect of hypertension and diabetes on median nerve using high-resolution ultrasound. METHODS: The study includes 50 hypertensive patients (HTN group), 50 diabetic patients (DM group), 50 patients with coexisting diabetes and hypertension (HTN + DM group) and 50 healthy controls. Median nerve affection in the studied groups was studied by vibration perception thresholds (VPT). The median nerve cross-sectional area was determined at the nerve cross-sectional area of the median nerve at the carpal tunnel by high-resolution ultrasound. Clinical symptoms were assessed using Toronto Clinical Severity Score (TCSS). RESULTS: There was significantly higher median nerve CSA in all patient groups in comparison to controls. HTN + DM group had significantly higher median nerve CSA when compared with DM group. Patients with peripheral neuropathy in HTN + DM and DM groups had significantly higher median nerve CSA than patients without. Using ROC curve analysis, it was shown that median CSA could successfully distinguish patients with peripheral neuropathy from patients without in HTN + DM group [AUC (95% CI): 0.71 (0.54-0.89)] and in DM group [AUC (95% CI): 0.86 (0.72-0.99)]. CONCLUSION: Hypertensive patients with and without diabetes have significantly higher median nerve CSA when compared with controls.

The Interplay between Zinc, Vitamin D and, IL-17 in Patients with Chronic Hepatitis C Liver Disease.

OBJECTIVES: To assess zinc (Zn) and vitamin D (Vit. D) status in chronic Hepatitis C virus- (HCV) infected patients and their relationship to interleukin- (IL-) 17 and disease severity and then investigate whether Zn and Vit. D3 modulate IL-17 expression in chronic HCV patients. METHODS: Seventy patients and fifty healthy subjects were investigated. Serum levels of Zn, Vit. D, and IL-17 were assessed in the patients group and subgroups. Patients lymphocytes were activated in vitro in the presence or absence of Zn or Vit. D3 and then intracellular IL-17 production was assessed using flow cytometry. RESULTS: Zn and Vit. D were significantly decreased in HCV patients. Increasing disease severity leads to more reduction in Zn level opposed by increasing IL-17 level. Zn potently reduced IL-17 production in a dose-related fashion; however it did not exert any toxic effects. Although Vit. D apparently increases IL17 expression, it is unclear whether it is due to its toxic effect on cell count or lack of definite association between Vit. D and both IL-17 and disease severity. CONCLUSIONS: This study demonstrates that Zn modulates IL-17 expression and provides a rationale for evaluating this compound as a supplementary agent in the treatment of chronic HCV.

Simultaneous injection of autologous mononuclear cells with TACE in HCC patients; preliminary study.

BACKGROUND: The discovery of the pluripotent stem cells made the prospect of cell therapy and tissue regeneration a clinical reality, especially with the evidence of contribution of the stem cells of bone marrow origin in hepatic regeneration. Infusion of bone marrow stem cells before trans-arterial chemoembolization may help to increase liver volume and consequently increase hepatic reserve in patients with HCC, and this may improve the outcome of this procedure. MATERIALS AND METHODS: Four Child B class patients with unresectable hepatocellular carcinoma treated by transarterial chemoembolization were injected with autologous bone marrow mononuclear layer containing stem cell in the hepatic artery feeding the contralateral lobe of the liver in the same session, follow-up of the patients was done by doing liver profile and CT liver volumetry before the surgery and 3 months later. RESULTS: We observed that patients receiving stem cell therapy simultaneously with TACE had shown a significant improvement in biological and volumetric parameters of liver function compared to those historically reported of patients receiving TACE only who usually shows deterioration of liver parameters. CONCLUSION: BMC infusion into the hepatic artery synchronized with TACE for patients with chronic liver disease complicated with HCC is safe, feasible, and demonstrated an improvement in both biological and radiological volumetric parameters.