Anesthesiology, October 22 edition

This ambidirectional cohort study evaluated eight cognitive measures in 77 children aged 9–11 years with or without previous surgical general anesthesia exposure. Overall executive-function performance did not differ significantly, but exposed children were less likely to belong to an efficient executive-control profile and showed altered global–local visuospatial processing.

Impact: The study moves beyond crude global cognitive scores and identifies a potentially subtle neurocognitive phenotype that may be missed by conventional testing. Its findings are clinically important because they refine, rather than exaggerate, the current understanding of long-term pediatric anesthesia risk.

Clinical Implications: Routine avoidance of necessary anesthesia cannot be justified by these findings, because overall executive function was not reduced. However, children with repeated or clinically concerning exposures may warrant longitudinal, domain-specific neurodevelopmental follow-up rather than reliance on global cognitive screening alone.

Future Directions: Larger prospective multicenter cohorts should incorporate pre-exposure developmental assessments, cumulative anesthetic dose and number of exposures, surgical indications, socioeconomic factors, and longer follow-up. Repeated domain-specific testing may determine whether the identified phenotype persists or predicts functional outcomes.

This multinational propensity-matched target trial emulation included 21,948 adults undergoing general anesthesia. Preoperative GLP-1 receptor agonist use was associated with fewer pulmonary adverse events and respiratory failure, but with a small increase in gastrointestinal adverse events, providing real-world evidence against a broad assumption of increased pulmonary risk.

Impact: Perioperative withholding recommendations for GLP-1 receptor agonists have been driven largely by aspiration concerns and limited case-based evidence. This large, contemporary analysis directly informs the risk–benefit debate, although it cannot replace prospective studies measuring gastric contents or aspiration events.

Clinical Implications: The findings support individualized rather than automatic discontinuation of GLP-1 receptor agonists before general anesthesia. Clinicians should still consider dose escalation, gastrointestinal symptoms, fasting duration, diabetes control, aspiration risk, and procedure urgency when deciding whether to continue or withhold therapy.

Future Directions: Prospective multicenter studies should stratify by GLP-1 receptor agonist class, dose-escalation phase, diabetes status, gastrointestinal symptoms, and fasting strategy. Studies should directly assess gastric contents and aspiration-related outcomes while comparing continuation with risk-stratified interruption.

In a 15-month-old mouse model of postoperative cognitive dysfunction, cGAS-STING pathway activation was accompanied by reduced tight-junction proteins, increased blood-brain barrier permeability, and impaired cognition. Pharmacologic inhibition with RU.521 improved these abnormalities, whereas STING activation with diABZI aggravated them, supporting a mechanistic and potentially targetable role for this pathway.

Impact: The study links innate immune DNA-sensing to postoperative cognitive dysfunction through a specific blood-brain barrier mechanism in aged animals. Bidirectional pharmacologic manipulation strengthens causal inference and provides a testable basis for future neuroprotective interventions.

Clinical Implications: The findings identify cGAS-STING signaling as a possible future therapeutic target for postoperative cognitive dysfunction, particularly in older patients. They do not yet support clinical use of cGAS or STING modulators because efficacy, pharmacokinetics, safety, and effects on infection and wound healing remain untested in humans.

Future Directions: Future studies should replicate the findings in aged female animals and multiple surgical models, define the cellular sources of cGAS-STING activation, and test selective pathway modulation with long-term cognitive, infection, wound-healing, and survival outcomes. Human studies should examine whether circulating or cerebrospinal biomarkers reflect this pathway.