Human macrophages and monocyte-derived dendritic cells stimulate the proliferation of endothelial cells through midkine production.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications

The Seroprevalence of Hepatitis C Virus (HCV) in Hemodialysis Patients in Oman: A National Cross-Sectional Study

Abstract Background HCV infection in hemodialysis units is a significant cause of morbidity and mortality. The risk of HCV infection among dialysis patients is higher compared to the general population due to high potential blood exposures in hemodialysis settings. This study aims to assess the national HCV seroprevalence in selected dialysis units and to determine the risk factors for acquiring HCV infection. Methods This cross-sectional study was conducted from 1 January to 31 March 2021. A total of 734 patients from 11 hemodialysis centers in Oman were included. Samples were tested simultaneously for HCV antibodies and HCV RNA. HCV genotyping was determined in all viremic patients. Demographic and hemodialysis center related data were gathered and their association with the positive HCV serology were explored using univariate and multivariate logistic regression analysis. Results Out of 800 patients selected from 11 dialysis units for the study, 734 patients (91.8%) were included. The overall seroprevalence of HCV infection among hemodialysis patients was 5.6%. (41/734). HCV RNA was detected in 31.7% (13/41) of seropositive hemodialysis patients. The most common genotype was subtype 1a, followed by subtype 3. Variables associated with high HCV prevalence were family history of HCV and duration of dialysis. Conclusion The prevalence of infection within hemodialysis patients in Oman has significantly decreased but remained higher than the general population. Continuous monitoring and follow-up, including periodic serosurvey and linkage to care and treatment are recommended. Additionally, practice audits are recommended for identifying gaps and ensuring sustainability of best practices and further improvement

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population