Anesthesiology Research Analysis
January’s anesthesiology research converged on translational immuno‑inflammation and precision perioperative care. A mechanistic sepsis program defined a druggable neutrophil EGFR–MAPK14–CEBPβ–PGLYRP1–TREM1 circuit and, separately, showed endothelial protection by neutralizing truncated procalcitonin—together pointing to vascular‑ and neutrophil‑targeted therapies. Resolution‑focused analgesia advanced with Protectin DX (GPR37‑dependent) shortening postoperative pain in preclinical models. Clini
Summary
January’s anesthesiology research converged on translational immuno‑inflammation and precision perioperative care. A mechanistic sepsis program defined a druggable neutrophil EGFR–MAPK14–CEBPβ–PGLYRP1–TREM1 circuit and, separately, showed endothelial protection by neutralizing truncated procalcitonin—together pointing to vascular‑ and neutrophil‑targeted therapies. Resolution‑focused analgesia advanced with Protectin DX (GPR37‑dependent) shortening postoperative pain in preclinical models. Clinically, a double‑blind RCT found nebulized salbutamol superior to glucose–insulin for preventing reperfusion hyperkalemia in liver transplantation, while deep‑learning analysis of newborn dried blood spots delivered a validated metabolic health index for early neonatal risk stratification.
Selected Articles
1. EGFR orchestrates neutrophil activation and NETosis via CEBPβ-dependent PGLYRP1 induction.
A translational mechanistic study mapped an EGFR–MAPK14–CEBPβ–PGLYRP1–TREM1 circuit in neutrophils that drives pathological NETosis and organ injury in sepsis; neutrophil-specific EGFR deletion mitigated cytokine storm, NETs, tissue damage, and improved survival in mice.
Impact: Defines a druggable neutrophil-intrinsic signaling axis linking receptor activation to NETosis, providing concrete targets (EGFR, MAPK14, PGLYRP1/TREM-1) for sepsis immunomodulation.
Clinical Implications: Enables target selection and biomarker-based stratification in sepsis trials (e.g., EGFR/PGLYRP1 expression), supporting development of EGFR modulators and TREM‑1 inhibitors.
Key Findings
- Neutrophil EGFR is upregulated in sepsis and correlates with severity.
- Neutrophil-specific EGFR knockout reduced cytokine storm, NETs, tissue injury, and improved survival in polymicrobial sepsis models.
- EGFR→MAPK14→CEBPβ drives PGLYRP1 transcription; PGLYRP1 amplifies NETosis via autocrine TREM-1 signaling.
2. Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis.
Protectin DX (PDX), a specialized proresolving mediator, shortened and resolved postoperative fracture pain more effectively than steroids/NSAIDs in mice; effects required GPR37, enhanced macrophage efferocytosis, and rapidly suppressed nociceptor activity.
Impact: Introduces a resolution-centric analgesic mechanism (PDX→GPR37) that may shorten pain duration rather than merely masking it, suggesting a new class of perioperative analgesics.
Clinical Implications: Supports development of PDX analogs and GPR37-targeted agents to accelerate pain resolution and reduce reliance on steroids/NSAIDs; early PK/safety and biomarker-guided stratification are warranted.
Key Findings
- IV PDX alleviated early and late postoperative pain phases and shortened overall pain duration.
- PDX outperformed PD1/DHA, steroids, and meloxicam; analgesia was absent in Gpr37−/− mice.
- Mechanism: GPR37 binding → macrophage Ca2+ signaling and efferocytosis; suppression of nociceptor C-fiber/DRG responses.
3. Quantitative assessment of neonatal health using dried blood spot metabolite profiles and deep learning.
From 13,536 newborn dried blood spots, a deep‑learning metabolic health index stratified risks of BPD, IVH, NEC, and ROP independent of gestational age and birthweight and was externally validated in 3,299 very preterm infants.
Impact: Demonstrates a generalizable, biologically grounded prognostic metric from routine specimens with direct implications for early neonatal surveillance and resource allocation.
Clinical Implications: Integration into neonatal workflows could guide targeted monitoring and early interventions beyond GA/BW triage, informing perioperative planning for high‑risk infants.
Key Findings
- Deep-learning index stratified BPD, IVH, NEC, and ROP risks independent of GA/BW.
- Outperformed alternative ML/clinical models and reproduced metabolic risk subgroups on external validation.
- Demonstrated feasibility of leveraging routine screening biospecimens for robust prognostics.
4. Comparison of nebulized salbutamol and glucose-insulin for preventing acute hyperkalemia in liver transplantation: a randomized, double-blind trial.
In 100 liver transplant recipients with baseline K ≥4 mmol/L, prophylactic nebulized salbutamol reduced hyperkalemia 30 seconds after reperfusion compared with glucose–insulin, with greater potassium decreases, milder glycemic swings, and fewer postoperative atelectasis events.
Impact: Offers a simple, immediately actionable prophylaxis to blunt potentially lethal reperfusion potassium surges in transplantation.
Clinical Implications: Consider nebulized salbutamol as first‑line prophylaxis against reperfusion hyperkalemia, especially when hyperglycemia is undesirable or insulin–glucose is contraindicated; refine dosing/timing with multicenter validation.
Key Findings
- Lower hyperkalemia incidence at 30 s post-reperfusion versus glucose–insulin (36% vs 56%).
- Greater maximum potassium decrease and milder glucose fluctuations with salbutamol.
- Fewer postoperative atelectasis events without increasing postreperfusion syndrome.
5. Endothelial cell responses in sepsis are attenuated by targeting truncated procalcitonin.
Neutralizing truncated procalcitonin preserved endothelial barrier function, mitigated vasoplegia, maintained endothelial NO bioavailability, and improved organ-level outcomes in sepsis models, reducing >50% of endothelial transcriptomic perturbations and dampening IL‑17 pathway signaling.
Impact: Links a widely measured clinical biomarker to a druggable endothelial-protective mechanism, opening a translational path for vascular-focused sepsis therapy.
Clinical Implications: Supports development of anti‑procalcitonin biologics to preserve endothelial integrity and reduce vasoplegia in septic shock; next steps include pharmacology, large‑animal safety, and early human studies.
Key Findings
- Anti-procalcitonin reduced endothelial transcriptomic changes by >50% and preserved lung/intestinal barriers.
- Mitigated vasoplegia and preserved endothelial NO bioavailability, improving organ integrity.
- Mechanistically associated with reduced IL‑17 pathway signaling in sepsis.