Explore the vast range of titles available.

Background This matters arising article addresses the recently published article in BMC Medicine by Cui et al., titled “Prophylactic effect of intraoperative sodium oxybate on postoperative delirium in older patients undergoing major orthopedic surgery: a randomized clinical trial.” Main body The work by Cui et al. demonstrated that intraoperative administration of sodium oxybate only significantly reduced postoperative delirium (POD) incidence in the participants undergoing morning surgery but not in those with afternoon surgery. Although this trial provided evidence that sodium oxybate may reduce POD, we raise several concerns regarding methodology and generalizability, such as incomplete control of perioperative risk factors, underestimated incidence of POD, subgroup analysis without multiple adjustments of confounding factors, and inadequate postoperative pain strategy. To verify the findings of this trial in further researches, we advocate the implementation of multi-center randomized clinical trials with large sample sizes, strict control of perioperative confounding factors, precise assessment of POD episodes, and the inclusion of subgroup analysis with multiple adjustments. Conclusion This matters arising does not seek to deny the results of Cui et al.’s trial. The main purpose of the authors is to emphasize that above methodological refinements are crucial for translating this valuable evidence into generally clinical practice and improving final outcomes of patients.

To the editor

Objective: To explore the role and mechanism of the Kelch sample related protein-1-nuclear factor erythroid-2 related factor 2/antioxidant response element (Keap1-Nrf2/ARE) signaling pathway in protection of dexmedetomidine (DEX) preconditioning against myocardial ischemia/reperfusion injury (MIRI). Methods: A total of 70 male SD rats were randomly divided into seven equal groups (n=10): blank control (S group), ischemia/reperfusion injury (C group), DEX preconditioning (DEX group), tertiary butylhydroquinone (tBHQ) control (tBHQ group), combined tBHQ and DEX preconditioning (tBHQ+DEX group), all-trans retinoic acid (ATRA) control (ATRA group), and combined ATRA and DEX preconditioning (ATRA+DEX group). Serum creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) concentrations were measured by ELISA kits, and the infarct size (IS) was assessed by Evan’s blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Oxidative stress was assessed through Western blotting for expression of Keap1-Nrf2/ARE pathway members and oxidative stress markers. Results: Cardioprotection of DEX, tBHQ, and tBHQ+DEX preconditioning treatments were shown as lower concentrations of serum CK-MB and cTnI and a smaller IS following MIRI in rats compared with those of MIRI rats without pre-treatment. In addition, tBHQ+DEX preconditioning exhibited stronger myocardial protection compared with DEX preconditioning. Mechanistically, the cardioprotection offered by DEX, tBHQ, and tBHQ+DEX preconditioning treatments was mediated via exerting antioxidant stress through activation of the Keap1-Nrf2/ARE signal transduction pathway. Conversely, the protective effects of DEX were diminished by blocking the Keap1-Nrf2/ARE pathway with inhibitor ATRA. Conclusion: DEX preconditioning protects against MIRI by exerting antioxidant stress through activation of the Keap1-Nrf2/ARE signal transduction pathway, while inhibition of the Keap1-Nrf2/ARE signal transduction pathway reverses the protective effect of DEX preconditioning on MIRI.

The letter to the editor was written in response to the recent article by Wang et al. “The influence of low-dose s-ketamine on postoperative delirium and cognitive function in older adults undergoing thoracic surgery”, which is published in Journal of Cardiothoracic Surgery. 2024; 19(1):324. This article concludes that intravenous low-dose S-ketamine during thoracic surgery in older patients significantly reduces the incidences of postoperative delirium and cognitive dysfunction, indicating a potential neuroprotective effect of intraoperative low-dose S-ketamine. In view to the retrospective nature of this study and their inconsistent findings with the results of a recent randomized controlled trial performed in patients undergoing non-cardiac thoracic surgery, we believe that several methodological issues and potential confounders in this study deserve further clarification and discussion before accepting their conclusions. Our main concerns include lacking the times and number of delirium monitoring per postoperative day, alone use of the Confusion Assessment Method form for delirium screening, not providing the factors related to the occurrence of postoperative delirium in the ICU stay, and application of a non-standard definition for postoperative cognitive impairment. We believe that clarification of these issues is useful for improving the transparency of their methodology and facilitating the interpretation of their results.