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Background: In addition to their classic genomic effects, glucocorticoids also manifest rapid non genomic effects. We speculate that dexamethasone has the potential prompt onset of analgesic effects. The objective of this study is to investigate the influence of a single preoperative dose of dexamethasone on the half maximal effective concentration (EC50) of remifentanil when combined with dexmedetomidine for pain relief during pancreatic extracorporeal shockwave lithotripsy (P-ESWL). Methods: A total of 60 patients undergoing P-ESWL were enrolled and randomized at 1:1 ratio into the dexamethasone (DXM) group and the placebo group. Before anesthesia induction, patients in DXM group received an intravenous injection of 8 mg dexamethasone, while subjects in placebo group received an equal dose of physiological saline. Monitored anesthesia care (MAC) was performed based on remifentanil in combination with dexmedetomidine. Remifentanil was administered by TCI with an initial target concentration of 2.5 µg/mL for both groups. A positive response was defined as that VAS score > 3 by the patient at any time during the procedure. Subsequent target concentrations were adjusted by Dixon up-down sequential method, where dose modifications were performed by 0.3 ng/mL intervals, based on the response of the previous patient. The EC50 of remifentanil for pain relief during P-ESWL treatment was calculated using Dixon's up-and-down method. Hemodynamic variables, oxygen saturation and adverse events were also recorded. Results: Dixon up-and-down method revealed that the EC50 of remifentanil was significantly higher in placebo group (2.65 ± 0.28 ng/mL) than in DXM group (2.02 ± 0.23 ng/ml) (P < 0.001). Hemodynamic parameter exhibited a significant decrease in mean arterial pressure (MAP) and heart rate (HR) before and after induction in placebo group; however, data of the two groups were comparable (P>0.05). Less adverse events occurred in DXM group, including the incidence of postoperative nausea and vomiting (PONV) and analgesia requirement with in the first 24 h following the procedure at ward. Conclusion: Dexamethasone exerted analgesic effects with a rapid onset, and patients received dexamethasone 8 mg preoperative had a lower required EC50 of remifentanil during P-ESWL. It is also associated with reduced PONV in addition to reduced postoperative analgesic consumption in the first postoperative 24 h. Trial registration: Registered in the Chinese Clinical Trial Registry (ChiCTR2300078171) on 30/11/2023. [ABSTRACT FROM AUTHOR]

Abstract: Background: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo . Methods: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture model was used to detect neutrophil migration, neutrophil extracellular traps level, and organ damage. Result: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of neutrophil extracellular traps, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multiorgan damage and lethality resulting from cecal ligation and puncture. Conclusions: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Sepsis is defined as life-threatening organ injury induced by infection, with high incidence and mortality. Sleep disorder is prevalent in septic patients and approximately 50% of patients with sepsis may develop atypical sleep patterns, but many of them may have been underdiagnosed by physicians. Sleep disorders and sepsis exhibit a close bidirectional relationship, with each condition significantly influencing the other. Conversely, sleep deprivation, sleep dysrhythmia and sleep fragmentation have been shown to impact the outcome of sepsis. This review endeavors to offer a comprehensive understanding of the intricate mechanisms that underpin the interplay between sepsis and sleep disorders, in addition to exploring potential clinical intervention strategies that could enhance outcomes for patients suffering from sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (© 2024 Guo et al.)

Background: Acute kidney injury (AKI) represents a significant complication following cardiac surgery, associated with increased morbidity and mortality rates. Despite its clinical importance, there is a lack of universally applicable and reliable methods for the early identification and diagnosis of AKI. This study aimed to examine the incidence of AKI after cardiac surgery, identify associated risk factors, and evaluate the prognosis of patients with AKI., Method: This retrospective study included adult patients who underwent cardiac surgery at Changhai Hospital between January 7, 2021, and December 31, 2021. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Perioperative data were retrospectively obtained from electronic health records. Logistic regression analyses were used to identify independent risk factors for AKI. The 30-day survival was assessed using the Kaplan-Meier method, and differences between survival curves for different AKI severity levels were compared using the log-rank test., Results: Postoperative AKI occurred in 257 patients (29.6%), categorized as stage 1 (179 patients, 20.6%), stage 2 (39 patients, 4.5%), and stage 3 (39 patients, 4.5%). The key independent risk factors for AKI included increased mean platelet volume (MPV) and the volume of intraoperative cryoprecipitate transfusions. The 30-day mortality rate was 3.2%. Kaplan-Meier analysis showed a lower survival rate in the AKI group (89.1%) compared to the non-AKI group (100%, P  < 0.001)., Conclusion: AKI was notably prevalent following cardiac surgery in this study, significantly impacting survival rates. Notably, MPV and administration of cryoprecipitate may have new considerable predictive significance. Proactive identification and management of high-risk individuals are essential for reducing postoperative complications and mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Wang, Bao, Lan, Zhao, Yang, Wang, Quan, Wang and Bian.)