Daily ReportSep 27, 2026
Anesthesiology, September 27 edition
We read 45 papers and selected 3.
Summary
The most impactful studies addressed postoperative cognitive vulnerability, pharmacological prevention of cardiac-surgery acute kidney injury, and the long-term neurodevelopmental safety of early-childhood general anesthesia. Together, they combine mechanistic discovery, a rigorously designed multicenter randomized trial, and a nationwide population-based cohort with direct implications for perioperative decision-making.
Research Themes
- Mechanisms and therapeutic targets for postoperative cognitive dysfunction
- Randomized evaluation of pharmacological renal protection in cardiac surgery
- Long-term neurodevelopmental outcomes after early-childhood general anesthesia
Selected Articles
1. 14-3-3γ Protects Against Postoperative Cognitive Dysfunction by Regulating Tau Thr205 Phosphorylation and Synaptic Integrity.
CSF proteomics identified 14-3-3γ as a candidate biomarker associated with neurodegenerative cognitive vulnerability, and plasma levels were associated with postoperative cognitive dysfunction and postoperative delirium. In mice, surgery and anesthesia reduced hippocampal 14-3-3γ, increased Tau Thr205 phosphorylation, impaired synaptic function, and worsened cognition; overexpression or pharmacological stabilization of the 14-3-3γ–Tau interaction reversed these abnormalities.
Impact: This study links human biomarker discovery to causal mechanistic experiments and identifies a potentially actionable 14-3-3γ–Tau pathway. It advances postoperative cognitive dysfunction research beyond association toward a testable therapeutic mechanism.
Clinical Implications: Circulating 14-3-3γ may eventually support perioperative cognitive-risk stratification, although it is not ready for clinical use. The 14-3-3γ–Tau interaction provides a rationale for future targeted therapies to prevent or treat postoperative cognitive dysfunction and delirium.
Key Findings
- CSF proteomics identified 14-3-3γ as a biomarker associated with neurodegeneration-enriched cognitive vulnerability.
- Plasma 14-3-3γ levels were associated with postoperative cognitive dysfunction and postoperative delirium in a prospective surgical cohort.
- In mice, 14-3-3γ overexpression or pharmacological stabilization of its interaction with Tau reduced Tau Thr205 phosphorylation, restored synaptic function, and improved cognition.
Methodological Strengths
- Integrated human proteomics, prospective perioperative biomarker assessment, and multiple mechanistic experimental systems.
- Used genetic rescue, pharmacological intervention, and a Tau phosphorylation mutant to support pathway specificity.
Limitations
- The human cohorts establish associations but cannot definitively prove that 14-3-3γ changes cause postoperative cognitive dysfunction.
- The therapeutic experiments were conducted in mice and neuronal models, so human efficacy, dosing, and safety remain unestablished.
Future Directions: Prospective multicenter studies should validate 14-3-3γ as a perioperative biomarker, define its relationship with delirium and long-term cognitive decline, and test 14-3-3γ–Tau stabilizers in translational safety and efficacy studies.
BACKGROUND: 14-3-3γ is implicated in neurodegeneration, yet its role in postoperative cognitive dysfunction (POCD) remains unclear. METHODS: We performed CSF proteomic profiling using the SomaScan 7K platform in the Alzheimer's Disease Neuroimaging Initiative cohort (n = 237) to identify biomarkers associated with neurodegeneration-enriched cognitive vulnerability (NECV). A prospective surgical cohort (n = 213) was used to evaluate circulating 14-3-3γ levels in relation to perioperative cognitive outcomes. Mechanistic studies were conducted using a murine surgery model, AAV-mediated gene manipulation, neuronal cultures, pharmacological intervention, and molecular dynamics simulations.
2. Efficacy of perioperative recombinant human brain natriuretic peptide for preventing acute kidney injury after cardiac surgery: Rationale, design, and study protocol for a multicenter, double-blind, randomized controlled trial (PROTECT-CS).
PROTECT-CS is an investigator-initiated, multicenter, double-blind, placebo-controlled randomized trial designed to test whether perioperative recombinant human brain natriuretic peptide prevents acute kidney injury after high-risk on-pump cardiac surgery. The planned sample is 694 patients, with Kidney Disease: Improving Global Outcomes-defined acute kidney injury within 7 days as the primary endpoint and clinically meaningful renal and mortality outcomes as secondary endpoints.
Impact: This protocol addresses a major unmet need with a properly powered, multicenter randomized design and clinically meaningful kidney outcomes. Its results could directly inform perioperative renal-protection practice and guidelines, whether positive or negative.
Clinical Implications: The trial will determine whether rhBNP should be incorporated into perioperative management for patients at high risk of cardiac-surgery acute kidney injury. Until results are available, routine prophylactic use should not be assumed.
Key Findings
- The trial plans to randomize 694 high-risk patients undergoing elective on-pump cardiac surgery.
- Patients receive rhBNP at 0.01 µg/kg/min or matched saline from anesthesia induction through 48 ± 2 postoperative hours.
- The primary endpoint is acute kidney injury within 7 postoperative days using Kidney Disease: Improving Global Outcomes criteria, with renal replacement therapy, MAKE-30, MAKE-90, mortality, and length of stay as secondary outcomes.
Methodological Strengths
- Multicenter, prospective, randomized, double-blind, placebo-controlled design with planned adequate statistical power.
- Uses standardized KDIGO acute kidney injury criteria and patient-important renal and mortality outcomes.
Limitations
- This publication reports the study protocol and provides no efficacy or safety results.
- The findings may be most applicable to selected high-risk patients undergoing elective on-pump cardiac surgery and may not generalize to emergency surgery or other cardiac procedures.
Future Directions: Completion of PROTECT-CS should establish whether rhBNP reduces acute kidney injury and major adverse kidney events, while prespecified subgroup analyses should assess effects according to baseline renal function, surgical risk, and cardiopulmonary bypass characteristics.
BACKGROUND: Acute kidney injury (AKI) is one of the most common and consequential complications after cardiac surgery. Despite improvements in perioperative care, no pharmacological intervention has been definitively shown to prevent AKI following cardiac surgery. Recombinant human brain natriuretic peptide (rhBNP) shares structural and biological activity with endogenous brain natriuretic peptide and has demonstrated favorable natriuretic, diuretic, and renal hemodynamic effects in prior studies. However, robust randomized evidence on whether perioperative rhBNP can prevent AKI is lacking. DESIGN: This is an investigator-initiated, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group trial comparing perioperative rhBNP with placebo in high-risk patients undergoing elective on-pump cardiac surgery.
3. Long-term neurodevelopmental and psychiatric risks after general anesthesia in early childhood: a nationwide population-based cohort study.
In a South Korean national cohort of 1,116,195 children, exposure to general anesthesia before age 3 was associated with a modestly increased risk of neurodevelopmental disorders diagnosed from age 3 through adolescence after propensity-score matching. The strongest associations were observed for intellectual disability and autism spectrum disorder, but the observational design cannot exclude residual confounding by the underlying condition, surgery, or other unmeasured factors.
Impact: The very large population, long follow-up, broad neurodevelopmental outcome assessment, and attempts to account for surgical complexity make this one of the more informative observational studies on a major pediatric anesthesia-safety concern. Its cautious interpretation is important for balancing potential risk against the benefits of necessary surgery.
Clinical Implications: The findings support careful counseling and avoidance of unnecessary procedures or anesthesia exposure in very young children, but they do not justify withholding clinically indicated anesthesia. Decisions should remain individualized, considering disease severity, surgical necessity, exposure duration, and alternative management options.
Key Findings
- The source population included 1,116,195 children born in South Korea between 2005 and 2007, with outcomes assessed through 2023.
- In the matched cohort of 131,699 children, general anesthesia before age 3 was associated with neurodevelopmental disorders with a hazard ratio of 1.19 (95% CI, 1.12-1.26).
- The largest reported associations were for intellectual disability, with a hazard ratio of 1.56, and autism spectrum disorder, with a hazard ratio of 1.46.
Methodological Strengths
- Nationwide population-based data provided a very large sample and long-term follow-up through adolescence.
- Used 1:5 propensity-score matching, stratified Cox regression, multivariable adjustment, and an administrative proxy for surgical complexity.
Limitations
- Residual confounding by the underlying illness, indication for surgery, perioperative physiology, socioeconomic factors, and unmeasured exposures cannot be excluded.
- Administrative diagnostic codes may incompletely capture neurodevelopmental phenotypes, anesthesia details, dose, duration, and cumulative exposure.
Future Directions: Future studies should use prospective multicenter designs with detailed anesthetic exposure, surgical indication, perioperative physiology, developmental testing, and sibling or negative-control comparisons. Mechanistic and exposure-response analyses are needed to distinguish anesthesia-related effects from disease and surgery-related risks.
PURPOSE: Pre-clinical evidence suggests that general anesthesia (GA) may have neurotoxic effects on the developing brain, but clinical findings remain inconsistent. Most studies have had limited follow-up or focused on selected neurodevelopmental outcomes, and residual confounding related to surgery remains difficult to address. We investigated the association between GA exposure before age 3 and a broad spectrum of neurodevelopmental disorders (NDDs) diagnosed through adolescence. METHODS: Using the South Korean National Health Insurance Service database, we identified 1,116,195 children born between 2005 and 2007. We compared children exposed to GA before age 3 with unexposed controls. The primary outcome was a new NDD diagnosis from the third birthday through 2023. Statistical analyses included 1:5 propensity-score matching with stratified Cox proportional hazards regression and multivariable Cox regression incorporating Total Relative Value Units (TRVUs) as an administrative proxy for surgical complexity.