Passive States for Essential Observers

The aim of this note is to present a unified approach to the results given in \cite{bb99} and \cite{bs04} which also covers examples of models not presented in these two papers (e.g. $d$-dimensional Minkowski space-time for $d\geq 3$). Assuming that a state is passive for an observer travelling along certain (essential) worldlines, we show that this state is invariant under the isometry group, is a KMS-state for the observer at a temperature uniquely determined by the structure constants of the Lie algebra involved and fulfills (a variant of) the Reeh-Schlieder property. Also the modular objects associated to such a state and the observable algebra of an observer are computed and a version of weak locality is examined.Comment: 27 page

Reliability of Admission Procalcitonin Testing for Capturing Bacteremia Across the Sepsis Spectrum: Real-World Utilization and Performance Characteristics, 65 U.S. Hospitals, 2008-2017

OBJECTIVES: Serum procalcitonin is often ordered at admission for patients with suspected sepsis and bloodstream infections (BSIs), although its performance characteristics in this setting remain contested. This study aimed to evaluate use patterns and performance characteristics of procalcitonin-on-admission in patients with suspected BSI, with or without sepsis. DESIGN: Retrospective cohort study. SETTING: Cerner HealthFacts Database (2008-2017). PATIENTS: Adult inpatients (≥ 18 yr) who had blood cultures and procalcitonin drawn within 24 hours of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Testing frequency of procalcitonin was determined. Sensitivity of procalcitonin-on-admission for detecting BSI due to different pathogens was calculated. Area under the receiver operating characteristic curve (AUC) was calculated to assess discrimination by procalcitonin-on-admission for BSI in patients with and without fever/hypothermia, ICU admission and sepsis defined by Centers for Disease Control and Prevention Adult Sepsis Event criteria. AUCs were compared using Wald test and p values were adjusted for multiple comparisons. At 65 procalcitonin-reporting hospitals, 74,958 of 739,130 patients (10.1%) who had admission blood cultures also had admission procalcitonin testing. Most patients (83%) who had admission day procalcitonin testing did not have a repeat procalcitonin test. Median procalcitonin varied considerably by pathogen, BSI source, and acute illness severity. At a greater than or equal to 0.5 ng/mL cutoff, sensitivity for BSI detection was 68.2% overall, ranging between 58.0% for enterococcal BSI without sepsis and 96.4% for pneumococcal sepsis. Procalcitonin-on-admission displayed moderate discrimination at best for overall BSI (AUC, 0.73; 95% CI, 0.72-0.73) and showed no additional utility in key subgroups. Empiric antibiotic use proportions were not different between blood culture sampled patients with a positive procalcitonin (39.7%) and negative procalcitonin (38.4%) at admission. CONCLUSIONS: At 65 study hospitals, procalcitonin-on-admission demonstrated poor sensitivity in ruling out BSI, moderate-to-poor discriminator for both bacteremic sepsis and occult BSI and did not appear to meaningfully alter empiric antibiotic usage. Diagnostic stewardship of procalcitonin-on-admission and risk assessment of admission procalcitonin-guided clinical decisions is warranted

Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19

Spleen tyrosine kinase (SYK) is a previously unidentified therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial. We demonstrated that SYK inhibition was associated with reduced neutrophil activation, increased circulation of mature neutrophils (CD10+CD33-), and decreased circulation of low-density granulocytes and polymorphonuclear myeloid-derived suppressor cells (HLA-DR-CD33+CD11b-). SYK inhibition was also associated with normalization of transcriptional activity in circulating monocytes relative to healthy controls, an increase in frequency of circulating nonclassical and HLA-DRhi classical monocyte populations, and restoration of interferon responses. Together, these data suggest that SYK inhibition may mitigate proinflammatory myeloid cellular and soluble mediator responses thought to contribute to immunopathogenesis of severe COVID-19