Daily Anesthesiology Research Analysis
Analyzed 44 papers and selected 3 impactful papers.
Summary
Three impactful anesthesiology-relevant studies stood out: a meta-analysis shows preoperative left atrial reservoir strain robustly predicts postoperative atrial fibrillation after cardiac surgery; translational nanotherapy with T7-targeted liposomal irisin mitigates perioperative neurocognitive disorder via AMPK/PGC-1α; and single-cell transcriptomics links neonatal sevoflurane exposure to long-term dendritic impairment through post-transcriptional MAP2 reduction.
Research Themes
- Perioperative cardiovascular risk stratification
- Anesthetic neurotoxicity and neuroprotection
- Translational nanotherapeutics for postoperative cognitive disorders
Selected Articles
1. predictive value of preoperative left atrial strain parameters on postoperative atrial fibrillation in adults undergoing cardiac surgery: A systematic review and meta-analysis.
Across 24 observational studies (n=2242), lower preoperative LA reservoir strain strongly associated with POAF after cardiac surgery, with an optimal cutoff around 22–25% (AUC 0.69). Conduit and contraction strain rates were also lower in POAF, and heterogeneity was partly explained by sex, vendor, and filling pressures.
Impact: Provides quantitative thresholds for LA strain to stratify POAF risk, informing perioperative surveillance and prophylaxis planning in cardiac anesthesia settings.
Clinical Implications: Incorporating LA reservoir strain (cutoff ~22–25%) into preoperative echocardiographic assessment may improve POAF risk stratification, guiding intensified monitoring and tailored prophylaxis (e.g., beta-blockers, amiodarone, magnesium) in high-risk patients.
Key Findings
- Preoperative LA reservoir strain is significantly lower in patients who develop POAF (SMD -2.37; 95% CI -3.87 to -0.88; I2=94.5%).
- Optimal LA reservoir strain cutoff for predicting POAF is 22–25% with AUC 0.69, sensitivity 0.713, and specificity 0.679.
- Meta-regression identified sex, vendor platform, and E/e' as contributors to heterogeneity; LA strain rates (reservoir, conduit, contraction) were not consistently different.
Methodological Strengths
- Comprehensive multi-database search with clearly defined inclusion/exclusion criteria.
- Use of meta-regression to explore heterogeneity and reporting of diagnostic thresholds (cutoffs, AUC, sensitivity/specificity).
Limitations
- High heterogeneity across studies (I2 up to 94.5%) and reliance on observational designs.
- Vendor/platform differences and loading conditions (E/e') may limit generalizability; pooled AUC is moderate.
Future Directions: Prospective, standardized echocardiography protocols across vendors to validate universal cutoffs, and interventional trials testing LA strain-guided POAF prophylaxis.
OBJECTIVES: Preoperative left atrial (LA) strain parameters measured by 2-dimensional speckle tracking echocardiography have been used to predict postoperative atrial fibrillation (POAF) after cardiac surgery. The aim of this meta-analysis was to determine whether preoperative LA strain parameters predict POAF after cardiac surgery. METHODS: PubMed, Embase, Cochrane database, and Google Scholar were searched manually until 31st January, 2025. Studies where preoperative LA strain was used to predict POAF following cardiac surgery in adults were considered. Reviews, case series, case reports, and studies where patients were in preoperative atrial fibrillation were excluded. RESULTS: Twenty-four observational studies involving 2242 patients were included. Preoperative LA reservoir strain was significantly lower in patients with POAF vs those without POAF (standardized mean difference (SMD) -2.37; 95% confidence interval (CI) -3.87 to -0.88; I2= 94.5%). Preoperative LA conduit (SMD -0.73; 95% CI: -1.06 to -0.39; I2= 41.5%) and contraction (SMD -1.04; 95% CI -1.81 to -0.27; I2= 92.2%) strain rates were significantly lower in patients with POAF while preoperative LA reservoir, conduit and contraction strain rates were not different in patients with POAF vs no POAF. Meta regression for heterogeneity in reservoir strain was significant for gender, vendor platform and filling pressures (E/e'). The cut-off value of LA reservoir strain for predicting POAF was 22 to 25% (area under curve 0.69, specificity 0.679 (95% CI : 0.645 to 0.711), sensitivity 0.713 (95% CI: 0.675 to 0.743)). CONCLUSIONS: Preoperative LA reservoir, conduit, and contraction strain predict POAF in adults undergoing cardiac surgery.
2. T7 peptide-engineered liposomal Irisin mitigates PND progression through AMPK/PGC-1α signaling: multi-omic evidence of metabolic and epigenetic modulation.
A T7-targeted liposomal formulation of irisin demonstrated robust neuroprotection against PND by restoring mitochondrial function and activating AMPK/PGC-1α. Multi-omic analyses revealed epigenetic activation of metabolic and antioxidant programs (e.g., SIRT1/NFE2L2) and improved neuro-glial crosstalk, with in vivo functional and morphological benefits.
Impact: Introduces a mechanistically grounded, targeted nanotherapeutic approach for PND with convergent in vitro, in vivo, and multi-omic evidence.
Clinical Implications: While preclinical, the data support AMPK/PGC-1α activation and metabolic-epigenetic modulation as candidate neuroprotective strategies for perioperative cognitive decline, warranting early-phase clinical trials and biomarker-driven patient selection.
Key Findings
- T7@Lipo@Irisin achieved ~85% encapsulation efficiency and improved neuronal mitochondrial membrane potential, reduced ROS, and enhanced viability under oxidative stress.
- In PND mice, treatment improved Garcia neurological scores, preserved neuronal morphology, and reduced apoptosis.
- Integrated scATAC-seq/scRNA-seq and proteomics showed epigenetic activation of Sirt1/Nfe2l2 and upregulation of mitochondrial and synaptic pathways; SIRT1, NDUFS2, and BDNF were increased.
Methodological Strengths
- Convergent multi-omic validation (scATAC-seq/scRNA-seq/TMT proteomics) linking phenotype to mechanism.
- Demonstration of efficacy across in vitro neuronal models and in vivo PND mouse model with functional readouts.
Limitations
- Preclinical study with small human serum sample (n=16); clinical safety, pharmacokinetics, and brain delivery in humans remain untested.
- Long-term durability and off-target effects of T7-targeted liposomes require evaluation.
Future Directions: First-in-human dose-finding studies with pharmacokinetic/target engagement biomarkers, and comparative trials against existing neuroprotective strategies in high-risk surgical populations.
This study explored the molecular mechanisms by which T7 peptide-modified liposomal irisin (T7@Lipo@Irisin) alleviates perioperative neurocognitive disorders (PND) via regulation of the AMPK/PGC-1α metabolic pathway. T7@Lipo@Irisin nanoparticles were prepared by thin-film hydration and ultrasonic dispersion and showed favorable physicochemical performance, with an encapsulation efficiency of approximately 85%. Serum analysis of healthy donors (n = 10) and PND patients (n = 6) showed higher IL-6 and TNF-α and lower brain-derived neurotrophic factor (BDNF) in PND. In vitro, T7@Lipo@Irisin restored mitochondrial membrane potential, reduced reactive oxygen species (ROS) accumulation, enhanced Neuro-2a hippocampal neuron viability, and activated the AMPK/PGC-1α axis under oxidative stress. In a PND mouse model, it improved Garcia neurological scores, preserved neuronal morphology, and decreased apoptosis. Multi-omic integration of scATAC-seq/scRNA-seq and TMT-based proteomics demonstrated enhanced neuro-glial crosstalk, epigenetic activation of metabolic/antioxidant genes (e.g., Sirt1, Nfe2l2), and upregulated pathways (mitochondrial function, NAD-dependent metabolism, synaptic homeostasis). Proteomics confirmed upregulation of SIRT1, NDUFS2, and BDNF, forming a network linked to energy metabolism and neural repair. Collectively, T7@Lipo@Irisin mitigates PND by activating AMPK/PGC-1α to enhance mitochondrial function and stabilize the neuro-microenvironment.
3. Single-Cell Transcriptomics Reveals the Mechanism of Long-Term Neurodevelopmental Toxicity Following Sevoflurane Anesthesia.
Neonatal sevoflurane exposure produced persistent adult deficits in fine motor skills and spatial memory in mice, with transcriptomic dysregulation of cell-shape pathways and reduced dendritic complexity. MAP2 protein was decreased without mRNA reduction, implicating post-transcriptional mechanisms in anesthetic neurotoxicity.
Impact: Provides mechanistic, cross-species evidence linking early anesthetic exposure to long-term dendritic and cognitive abnormalities, refining targets for neuroprotection in pediatric anesthesia.
Clinical Implications: Highlights the importance of minimizing duration and depth of anesthesia in neonates/infants and motivates exploration of perioperative neuroprotective strategies targeting dendritic stability and post-transcriptional regulation.
Key Findings
- Neonatal sevoflurane exposure caused persistent adult impairments in fine motor ability and spatial memory in mice.
- Single-cell transcriptomics showed widespread gene expression changes without altering major cell-type composition; pathways related to cell shape were dysregulated.
- Dendritic complexity was reduced, and MAP2 protein decreased despite unchanged mRNA, indicating post-transcriptional regulation.
Methodological Strengths
- Integration of behavioral assays with single-cell transcriptomics and immunofluorescence.
- Cross-species approach leveraging human embryonic PFC single-cell data to complement mouse findings.
Limitations
- Preclinical mouse model; human causal inference remains indirect.
- Exposure paradigms may not fully match clinical dosing/duration; mechanistic rescue experiments are needed.
Future Directions: Test neuroprotective agents that stabilize dendrites or modulate post-transcriptional MAP2 regulation in clinically relevant anesthetic paradigms and validate biomarkers in pediatric cohorts.
Prolonged exposure to general anesthetics during early development has been associated with neurobehavioral deficits. Sevoflurane, a commonly used pediatric anesthetic, may disrupt cortical maturation, particularly in the prefrontal cortex (PFC) which plays a critical integrative and regulatory role in cognitive and motor functions. In this study, the long-term effects of neonatal sevoflurane exposure were examined using a mouse model, complemented by analysis of single-cell RNA sequencing data from human embryonic PFC (GSE196239). Behavioral assays showed that mice exposed to sevoflurane at postnatal day 7 exhibited persistent impairments in fine motor ability and spatial memory in adulthood. Transcriptomic analysis showed that sevoflurane induced widespread gene expression alterations without changing the major cell-type composition. Through enrichment analysis, dysregulation of pathways related to cell shape was identified. Consistent with these transcriptomic findings, reduced dendritic complexity was observed in sevoflurane-treated neurons by immunofluorescence. Notably, microtubule-associated protein 2 (MAP2), a key structural protein in dendrites, was significantly reduced at the protein level without a corresponding decrease in mRNA expression, suggesting the involvement of post-transcriptional regulation. Together, these findings suggest that prolonged neonatal sevoflurane exposure may impair neuronal maturation and dendritic architecture, and provide molecular insights into the long-term cognitive and motor alterations associated with neonatal sevoflurane exposure.