Blood levels of inflammatory markers associated with endothelial dysfunction and atherosclerosis are increased in diabetic patients; the highest levels occur in poorly controlled diabetes. We investigated the activation state of peripheral blood monocytes in diabetes with respect to scavenger receptor (CD36) expression and monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and peroxisome proliferator-activated receptors mRNA expression. CD14؉ monocytes were isolated from peripheral blood of type 1 and type 2 diabetic patients with good (HbA 1c <7.0%) or poor (>9.4%) glycemic control and a group of nondiabetic subjects. Monocytes from diabetic subjects displayed increased CD36 cell surface expression (P < 0.0005) and increased uptake of oxidized LDL (P < 0.05). Monocyte chemoattractant protein-1 gene expression was increased in monocytes from both groups of diabetic subjects (P < 0.05). Both CD68 and peroxisome proliferator-activated receptor-␥ gene expression were increased in the poorly controlled diabetic group (P < 0.05 for each), whose monocytes also displayed increased attachment to endothelial monolayers (P < 0.0005 vs. nondiabetic control subjects). In poorly controlled diabetes, CD14؉ monocytes are functionally activated and show some of the differentiation markers associated with macrophages. These monocytes also demonstrate an increased ability for attachment to normal endothelial cells, one of the early stages in atherogenesis. Diabetes 54:2779 -2786, 2005 I t has become clear that inflammatory processes play a major role in atherogenesis and that the endothelium is intimately involved at all stages of atheroma formation. With this has come a major change in our understanding of the function of the endothelium as a diffuse organ, involved in prevention of thrombosis and in modulation of both relaxation and contraction of the blood vessels (1,2). Raised levels of the inflammatory marker C-reactive protein (CRP) are associated with altered endothelial function and arterial stiffness in healthy individuals (3,4) and are predictive of future coronary heart disease in healthy middle-aged men (5). Views on the importance of inflammatory markers have progressed to the extent that it has been suggested by some that CRP is a stronger predictor of first cardiovascular events than LDL cholesterol (6); however, others suggest a more cautious interpretation of available data (7). In vitro studies have shown that CRP induces endothelial cells to produce the inflammatory cytokine interleukin-6 (IL-6), which, at least in part, is responsible for upregulation of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) (8). CRP also induces production of monocyte chemoattractant protein-1 (MCP-1) by both endothelial (8) and vascular smooth muscle (9) cells; MCP-1 enhances the movement of mononuclear cells into the subendothelial space.Although a great deal has been published on vessel wall stiffness and the prevalence of inflammator...

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Background Improving antibiotic stewardship whilst simultaneously optimizing patient safety is a perpetually vexing clinical conundrum, which has been compounded by the current COVID-19 pandemic. Procalcitonin (PCT) measurement has previously demonstrated utility in this regard, when combined with routine clinical investigation, in certain patient populations. Objectives To assess whether the inclusion of PCT measurement as part of routine clinical care, instituted during a quality improvement project (QIP), increases the appropriateness of antibiotic administration. Methods A retrospective analysis was performed on 6 month interim data obtained from May to October 2021 during a QIP, which assessed the effect of PCT measurement on antimicrobial stewardship. All patients included had a primary diagnosis of respiratory illness and were analysed both together and as COVID-19 and non-COVID-19 subgroups to assess how often antibiotics were commenced on admission, duration of treatment and appropriateness of use. Finally, as sending microbiological samples made up part of the protocol, sample sending frequency was also studied. Results Thirty patients were included in both the COVID-19 and non-COVID-19 baseline subgroups who did not have PCT testing performed. Fifty-two patients were included in the PCT subgroup (27 COVID-19 positive and 25 COVID-19 negative). Following introduction of PCT testing, commencement of antibiotics on admission was reduced overall and in the COVID-19 positive subgroup (P = 0.0426 and P = 0.0446, respectively) with a significant decrease in inappropriate antibiotic prescribing in these two groups (P = 0.011 and P = 0.0157, respectively) and a trend towards reduced prescribing of AWaRe watch group antibiotics such as ceftriaxone. However, once prescribed, there was no difference in duration of antibiotic treatment or the frequency of microbiological sampling. Conclusions The data from this interim data analysis demonstrate that PCT measurement, when combined with routine clinical investigations in the acute respiratory setting, can be used to reduce inappropriate antibiotic prescribing. This was significantly reduced overall and in the COVID-19 positive subgroup but lost statistical significance in the COVID-19 negative subgroup, where it could be hypothesized that heterogeneity and inclusion of respiratory diseases where PCT has previously encountered difficulty in determining the presence of acute bacterial infection may be the cause. The significant effect demonstrated in the COVID-19 positive subgroup suggests particular utility in this patient population.