Neutrophils play a vital role in human immune defense, and their dysregulation can cause collateral damage in sepsis and autoimmune diseases. We provide evidence for the involvement of the transient receptor potential vanilloid 2 (TRPV2) in cytokine expression and transmigration in human neutrophils as well as in HL60 cells. These data identify TRPV2 as a candidate target for novel therapeutics regulating neutrophil activity.

Background/Objectives: Pre-anesthetic consultations (PACs), conducted by anesthesiologists, are an established procedure to assess individual perioperative risk in surgical patients. Cancellation of surgery leads to unnecessary PACs, which have to be avoided in times of staff shortage. The aim of the study is to evaluate the costs and time loss of unnecessary PACs at Hannover Medical School, a university hospital in Germany. Methods: All PACs conducted at Hannover Medical School in September 2023 were included in the analysis. The duration and associated costs were calculated based on electronic documentation. Results were compared to data from the university hospital Aachen in Germany. Results: In 4.2% of all PACs, no surgical or interventional procedure was subsequently performed and therefore no anesthesiologic services were required. Reasons for surgery or intervention cancellation included choosing a conservative approach over surgery or proceeding with surgery under local anesthesia without the presence of an anesthesiologist. The additional costs for unnecessary PACs were EUR 1612 which corresponded to 43.2 h of working time. Projected over a year, this would result in EUR 19,344 in costs and 518.4 h of time spent. In comparison to university hospital Aachen, we observed lower cancellation rates after PACs and a greater reliability of the planned interventions and surgeries. Conclusions: The results of this study suggest that the financial and time burden associated with these consultations was not substantial. To ensure optimal use of temporal and financial anesthesiologic resources, it is essential to avoid PACs for patients who will not undergo surgery or intervention.

BACKGROUND: Cannabidiol (CBD) inhibits voltage-gated sodium channels (Na _v ). CBD is highly lipophilic and exhibits slow binding kinetics on Na _v s, a property that may enable CBD to enhance and prolong regional anesthesia. Here we explored the effects of CBD on lidocaine-induced Na _v -inhibition and neurotoxicity. METHODS: Patch clamp recordings were performed on tetrodotoxin (TTX)-sensitive Na _v s and the TTX-resistant Na _v 1.8 in ND7/23 cells or murine dorsal root ganglion neurons (DRG). Cytotoxicity was analyzed using flow cytometry. RESULTS: CBD induced a potent tonic inhibition of sodium currents with slow onset and offset kinetics. Na _v 1.8 exhibited a higher sensitivity to tonic block (IC ₅₀ 1.4 µM) as compared to TTX-sensitive sodium channels (IC ₅₀ 2.9 µM). Similar to local anesthetics, CBD also induced a shift of the steady-state inactivation and a modest use-dependent block at 10 Hz. In contrast to local anesthetics, inhibition of Na _v s by CBD is pH-independent. The co-application of CBD and lidocaine resulted in an additive tonic block of sodium currents in ND7/23 cells, but not in DRG neurons. While only high concentrations of CBD induced cytotoxicity, it potentiated lidocaine-induced cytotoxicity. CONCLUSIONS: CBD demonstrates promising characteristics as a long-lasting local anesthetic, or as an adjunct to local anesthetics used for regional or topical anesthesia.

Newborn individuals are highly susceptible to infectious diseases. For better insights into age-specific host-pathogen interactions infection models are increasingly employed in neonatal mice. However, for newborn mice no measures are available to objectify the clinical disease state, particularly not in a longitudinal manner, to meet legal animal welfare requirements. We developed a scoring system for newborn mice that relies on observational and examination-based parameters and validated it by applying a Staphylococcus aureus -induced infection model in two different mouse strains. The scoring results strongly correlated with the death kinetics independent of which mouse strain was used. A score above 7 predicted fatality. While the score values increased already at early sepsis stages the large majority of plasma cytokine levels remained comparable to those in uninfected control neonates. The levels of interleukin (Il)-6, chemokine C-C motif ligand 5, Il-1α and tumor necrosis factor α were not increased before 24 hours after infection and correlated only at this late stage of sepsis with the scored disease state. We propose the first clinical scoring system that serves as important research tool to evaluate the clinical course of sepsis in newborn mice. It detects health impairments of newborn pups in a highly sensitive and longitudinal manner, providing information about the disease severity as well as prognosis.