No abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces low density lipoprotein (LDL) uptake, leading to increased plasma levels of LDL. In addition, PCSK9 has been implicated in inflammation independently of the effects on cholesterol metabolism. The current analysis showed that our 156 patients with systemic inflammatory response syndrome (SIRS) or sepsis had higher plasma PCSK9 levels in contrast with the 68 healthy controls. COVID-19 sepsis patients had increased plasma PCSK9 levels in comparison to sepsis patients not infected by SARS-CoV-2. For further analysis, patients were divided in two groups based on COVID-19. In both sub-cohorts, plasma PCSK9 levels did not correlate with C-reactive protein, leukocyte count, and procalcitonin. Plasma PCSK9 levels of both patient groups did not significantly differ among SIRS/sepsis patients with and without dialysis and patients with and without ventilation. Furthermore, vasopressor therapy was not significantly associated with altered plasma PCSK9 levels. In the non-COVID-19 SIRS/sepsis group, patients with Gram-negative and Gram-positive infections had similar plasma PCSK9 levels as patients without a detectable pathogen in their blood. In conclusion, the current study suggests PCSK9 as a possible biomarker for COVID-19, but this needs to be validated in larger cohorts.

It is known that cimetidine inhibits the hypoxia-induced increase in cerebral blood flow (CFB) in dogs, but the mechanism of this inhibition is not fully understood. Since the accepted mechanisms explaining the increase in CBF during hypercapnia are very different from those active during hypoxia, acute hypercapnia was induced in 12 conscious dogs in order to study the cimetidine effect in this condition. Six dogs were given i.v. saline (control group) and the other six, i.v. cimetidine (4 mg kg-1). After 15 min, CBF and various muscular blood flow measurements were performed, using the microspheres technique under two conditions: (1) breathing air and (2) after 2 h inhalation of a gas mixture with FiCO2 0.10, FiO2 0.21 in nitrogen. The CBF increase was similar in both series with or without cimetidine. The changes in muscular blood flow were unaffected by the H2-blocker. We conclude that cimetidine has no effect on the CBF and on muscular blood flow during acute hypercapnia.

Chemerin is a chemoattractant protein abundantly expressed in hepatocytes. Chemerin exerts pro- and anti-inflammatory effects and acts as a pro-resolving protein. Chemerin levels are low in patients with liver cirrhosis and are increased in sepsis. The aim of this study was to identify associations between plasma chemerin levels and underlying diseases as well as causes of severe illness. The cohort included 32 patients with liver cirrhosis who had low systemic chemerin, and who were not considered for further evaluation. Plasma chemerin levels were similar between the 27 patients with systemic inflammatory response syndrome (SIRS), the 34 patients with sepsis and the 63 patients with septic shock. Chemerin in plasma correlated with C-reactive protein and leukocyte count but not with procalcitonin, a clinical marker of bacterial infection. Plasma chemerin did not differ among patients with and without ventilation and patients with and without dialysis. Vasopressor therapy was not associated with altered plasma chemerin levels. Infection with severe acute respiratory syndrome coronavirus 2 had no effect on plasma chemerin levels. Baseline levels of plasma chemerin could not discriminate between survivors and non-survivors. Notably, Gram-positive infection was associated with higher chemerin levels. In summary, the current study suggests that plasma chemerin might serve as an early biomarker for the diagnosis of Gram-positive infections in patients with sepsis.