Anesthesiology, September 2026 edition

This translational study integrated human proteomics, a prospective surgical cohort, and mechanistic cellular and murine experiments. Reduced or altered 14-3-3γ was associated with postoperative cognitive dysfunction and delirium, while surgery and anesthesia reduced hippocampal 14-3-3γ, increased Tau Thr205 phosphorylation, and impaired synaptic function in mice. Genetic overexpression or pharmacological stabilization of the 14-3-3γ–Tau interaction improved cognition and synaptic integrity.

Impact: The study moves postoperative cognitive dysfunction research from epidemiologic association toward a biologically defined and potentially druggable pathway. Its integration of human findings with genetic and pharmacological rescue experiments provides unusually strong mechanistic support for future biomarker and therapeutic development.

Clinical Implications: Circulating 14-3-3γ is not yet ready for clinical risk stratification, and targeted stabilizers are unavailable for patient care. Nevertheless, the findings support prospective biomarker studies and future therapeutic trials in patients at high risk of postoperative cognitive dysfunction or delirium.

In neonatal mice, repeated two-hour sevoflurane exposure on postnatal days 2–4, but not a single exposure, caused hypomyelination and persistent cognitive and fine-motor deficits. The effects were associated with enhanced CX3CL1/CX3CR1 signaling, Rac1-related cytoskeletal changes, and excessive microglial phagocytosis of oligodendrocyte precursor cells. Genetic CX3CR1 deletion attenuated the cellular and behavioral abnormalities.

Impact: This study provides convergent behavioral, cellular, molecular, structural, and genetic evidence linking repeated neonatal sevoflurane exposure to impaired myelination. It identifies a specific and potentially modifiable neuroimmune pathway rather than merely reporting an exposure-outcome association.

Clinical Implications: The findings support caution regarding repeated early-life anesthesia exposure and motivate biomarker and neuroprotective research. They do not establish harm in human infants and should not by themselves prompt immediate changes to clinical anesthesia practice.

This retrospective analysis describes A-QUA, a nationwide Swiss anesthesia quality program. By the end of 2024, its case-based registry contained 2,045,026 cases from 54 centers, enabling standardized benchmarking, detection of recurrent data-quality problems, and analysis of regional and hospital variation in anesthesia practice and postoperative disposition.

Impact: The registry demonstrates how standardized, nationwide anesthesia data can support continuous quality improvement and perioperative research at a scale rarely available in anesthesiology. Its value lies in infrastructure, reproducibility, and the ability to identify actionable variation rather than in a single clinical association.

Clinical Implications: Anesthesia departments and health systems can use comparable routine data to identify preventable documentation or process errors, benchmark practice patterns, target quality-improvement interventions, and generate hypotheses for prospective safety research.

PROTECT-CS is a multicenter, double-blind, placebo-controlled randomized trial protocol testing perioperative recombinant human brain natriuretic peptide in 694 high-risk patients undergoing elective on-pump cardiac surgery. The primary endpoint is KDIGO-defined acute kidney injury within seven days, with renal replacement therapy, MAKE-30, MAKE-90, mortality, and length of stay as important secondary outcomes. The protocol addresses the lack of proven pharmacologic prevention for cardiac-surgery acute kidney injury.

Impact: Although this is a protocol rather than an efficacy report, it is designed to answer a major unresolved perioperative question with multicenter randomization, blinding, and patient-important renal outcomes. A positive or negative result could directly influence cardiac-anesthesia renal-protection practice.

Clinical Implications: Routine prophylactic rhBNP should not be adopted before trial results are available. If effective and safe, rhBNP could become a targeted renal-protection strategy for selected high-risk cardiac-surgery patients; if ineffective, the trial will help prevent unsupported pharmacologic use.

Using auditory discrimination, AI-based pose analysis, fiber photometry, single-cell calcium imaging, and pathway-specific chemogenetic and optogenetic manipulation, this mouse study separated false auditory threat perception from disorganized behavior during S-ketamine exposure. The basolateral amygdala-to-caudal striatum pathway promoted salience-weighted false threat responses, whereas the medial prefrontal cortex-to-caudal striatum pathway shaped disorganized actions. Dexmedetomidine restored pathway timing and striatal network coupling.

Impact: The study offers a circuit-level framework for separating perception from behavioral expression in ketamine-related hallucination-like states. Its causal pathway experiments and pharmacologic rescue provide an unusually detailed basis for translational research on emergence phenomena and ketamine-associated behavioral disturbances.

Clinical Implications: The findings support further investigation of dexmedetomidine for ketamine-related perceptual or behavioral disturbances and may inform future studies of emergence delirium. Direct clinical use is premature because the evidence comes from an acute mouse model.