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Purpose: The purpose was to determine whether a simplified procalcitonin (PCT) algorithm guided by pharmacist recommendations reduces antibiotic duration of therapy in critically ill patients with suspected sepsis. Methods: This was a single-centered pre-post study conducted at a 1368-bed community teaching hospital in the United States. A prospective cohort with pharmacist intervention utilizing a simplified PCT algorithm was compared with a retrospective historical cohort with standard therapy. Adult patients admitted to the intensive care unit (ICU) with suspected sepsis who received intravenous antibiotics were included. A pharmacist recommended continuation or discontinuation of antibiotics based on the PCT level per our algorithm and full clinical assessment of the patient. Primary outcome was total duration of antibiotic therapy. Secondary outcomes were ICU and hospital length of stay (LOS), reinitiation of antibiotic therapy within 72 hours of discontinuation, and 28-day in-hospital mortality. Results: From September 2017 to May 2018, 360 patients were screened for eligibility. Of these, 26 patients were included in the PCT group and 26 patients in the standard therapy group. Baseline characteristics were similar between groups. A significant difference in duration of antibiotic therapy was detected with a median of 9 days in the PCT group versus 12 days in the standard therapy group ( P = .02). There were no significant differences in secondary endpoints of ICU and hospital LOS, reinitiation of antibiotics at 72 hours, or 28-day mortality. Conclusion: Use of a simplified PCT algorithm with pharmacist-guided recommendations significantly reduced the duration of antibiotic therapy in critically ill patients with sepsis.

Free radicals react with redox sensitive cysteines and form oxidative post translational modifications (Ox-PTM) which alters protein function. The effect of redox signalling on Jag1has not yet been investigated. However, we have identified Jag1 as a redox target in ECs. Additionally, this signalling regulates expression of proteins involved in adhesion, the cell cycle, and the extracellular matrix (ECM). An Iodo-TMT redox proteomics screen was performed to identify Ox-PTMs in ECs involved in vascular signalling mechanisms. A group of proteins involved in angiogenesis was identified including Jag1, one of the canonical Notch ligands. The patterning of blood vessel sprouts during angiogenesis is regulated by Notch-Jag interactions. Quantitative proteomics was performed to determine changes in protein expression between WT and a redox-insensitive variant of Jag1. This 'redox dead' (RD) variant was generated through cysteine to serine substitutions. Human umbilical vein ECs (HUVEC) transiently expressing these Jag1 variants were treated with H 2 O 2 or VEGF. Jag1RD downregulated proteins related to adhesion and the ECM while upregulating cell cycle proteins. Using the histone ruler method, protein content per cell was estimated. This showed lower protein in cells expressing Jag1RD compared to Jag1WT, correlating with an increased cell cycle rate. Results show that Jag1 redox modifications alter important EC processes which may be Notch-independent.

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