Daily Sepsis Research Analysis
Mechanistic and translational studies advance sepsis care along three fronts: preserving endothelial integrity, preventing device-associated thrombosis, and accelerating antimicrobial susceptibility testing. A mechanistic study links SGLT2 inhibition to ApoM preservation and reduced vascular leak; a nano-selenium hydrogel coating suppresses thrombosis even under septic conditions; and direct AST from positive blood cultures shows high agreement with standard methods while cutting turnaround by 2
Summary
Mechanistic and translational studies advance sepsis care along three fronts: preserving endothelial integrity, preventing device-associated thrombosis, and accelerating antimicrobial susceptibility testing. A mechanistic study links SGLT2 inhibition to ApoM preservation and reduced vascular leak; a nano-selenium hydrogel coating suppresses thrombosis even under septic conditions; and direct AST from positive blood cultures shows high agreement with standard methods while cutting turnaround by 24 hours.
Research Themes
- Endothelial barrier protection in systemic inflammation and sepsis
- Device-associated thrombosis mitigation under inflammatory/septic conditions
- Rapid antimicrobial susceptibility testing directly from positive blood cultures
Selected Articles
1. In situ self-growth nano-selenium hydrogel coating alleviates surface thrombosis of blood-contacting devices by inactivating inflammatory cells.
An in situ self-growing nano-selenium hydrogel coating reprogrammed macrophages (↓M1, ↑M2; +146% M2/M1) and reduced procoagulant activity (↓TF release, ↓thrombin). It suppressed coagulation and thrombus formation in an LPS-induced rabbit model and in patients with clinical sepsis, and reduced thrombosis and inflammatory activation on CVCs in rabbit and pig models.
Impact: Introduces a mechanistically grounded, anti-inflammatory device coating that mitigates thrombosis under intense inflammatory/septic conditions, spanning small and large animal models with translational signals in patients.
Clinical Implications: If validated clinically, such coatings could reduce catheter-related thrombosis and inflammation in critically ill and septic patients, potentially lowering complications and device failure. Implementation would require safety profiling (e.g., selenium exposure), durability testing, and infection-control assessment.
Key Findings
- Nano-selenium coating shifted macrophages toward an anti-inflammatory phenotype (M2/M1 ratio increased by 146%) and reduced pro-inflammatory cytokines.
- The coating decreased macrophage tissue factor release and thrombin production, suppressing coagulation in an LPS-induced rabbit model and in patients with clinical sepsis.
- Central venous catheters with the coating reduced thrombosis and vascular inflammatory activation in rabbit and pig vascular models.
Methodological Strengths
- Convergent evidence across in vitro assays, small (rabbit) and large (pig) animal models, and translational observations in septic patients.
- Mechanistic linkage to macrophage polarization and coagulation pathways (tissue factor/thrombin).
Limitations
- Human data are limited; no randomized clinical outcomes were reported.
- Long-term biocompatibility, durability, and potential selenium toxicity were not fully characterized.
Future Directions: Conduct multicenter safety and efficacy trials in high-risk ICU/sepsis populations, assess infection risk and device colonization, and optimize coating composition and growth parameters.
2. Sodium-Glucose Cotransporter Inhibition Preserves Apolipoprotein M During Acute Inflammation in Mice and Humans.
Dapagliflozin preserved ApoM during acute inflammation by maintaining renal LRP2, increased ApoM in randomized human participants, and reduced LPS-induced vascular leak in an ApoM-dependent manner. The findings provide a mechanistic link between SGLT2 inhibition, ApoM biology, and endothelial barrier integrity relevant to sepsis pathophysiology.
Impact: This is a novel mechanistic demonstration that SGLT2 inhibition preserves ApoM via LRP2 and stabilizes the endothelial barrier, connecting a widely used cardiometabolic drug class to a sepsis-relevant survival pathway.
Clinical Implications: Supports testing SGLT2 inhibitors as adjunctive therapy to preserve endothelial integrity in sepsis or systemic inflammation. ApoM may serve as a pharmacodynamic biomarker to enrich and monitor such trials.
Key Findings
- Dapagliflozin restored circulating ApoM in LPS-treated mice (0.017 vs 0.035 a.u./μL; P=0.0489).
- In randomized human participants receiving SGLT2 inhibitors, ApoM increased (0.5240 vs 0.6537 μM; P=0.0101).
- LRP2 knockout abrogated the ApoM effect; in vitro Lrp2-dependent ApoM uptake increased; vascular leak reduction was ApoM-dependent.
Methodological Strengths
- Triangulation across mouse models, randomized human cohort, and mechanistic in vitro assays.
- Genetic validation using proximal tubule-specific Lrp2 knockout.
Limitations
- Clinical outcomes (e.g., mortality, organ failure) were not assessed.
- Human sample size and sepsis-specific cohorts were not detailed; human data derived from COVID-19 context.
Future Directions: Randomized controlled trials in sepsis to test SGLT2 inhibitors for endothelial leak reduction and improved outcomes, with ApoM as a mechanistic biomarker.
3. Evaluation of BD Phoenix and VITEK 2 for direct and routine antimicrobial susceptibility from positive blood culture bottles.
In 128 ESKAPE isolates from positive blood cultures, direct AST (DAST) using BD Phoenix and VITEK 2 showed high categorical agreement with routine and standard testing. VITEK 2 was consistently reliable for Gram-negative bacteria, and BD Phoenix performed strongly for direct AST across organisms. Implementing DAST reduced turnaround time by 24 hours.
Impact: Rapid, accurate AST directly from positive blood cultures can accelerate effective therapy in sepsis, potentially improving outcomes while informing stewardship.
Clinical Implications: Clinical microbiology labs can adopt DAST workflows to shorten time-to-result by 24 hours. Platform choice may be tailored: VITEK 2 for Gram-negative reliability, BD Phoenix for robust direct testing performance, with local verification and protocols for discordance resolution.
Key Findings
- DAST vs RAST categorical agreement (BD Phoenix): 95.3% (Enterobacterales), 100% (non-fermenters), 100% (Gram-positive cocci).
- DAST vs RAST categorical agreement (VITEK 2): 94.8%, 94.7%, 80%, and 100% across Enterobacterales, non-fermenters, S. aureus, and Enterococci spp.
- RAST vs SAST categorical agreement: BD Phoenix 86.9%, 95.3%, 100%, 82.3%; VITEK 2 91.8%, 91.9%, 85.7%, 84.6% across the same groups; DAST reduced turnaround time by 24 hours.
Methodological Strengths
- Head-to-head comparison of two automated platforms using DAST, RAST, and SAST with explicit categorical agreement metrics.
- Focus on clinically relevant ESKAPE pathogens from positive blood cultures.
Limitations
- Single-laboratory methodology study with 128 isolates; external validity may be limited.
- Clinical impact (time to effective therapy, outcomes) not directly measured.
Future Directions: Multicenter validation including outcome-linked implementation studies; expand organism/antibiotic panels and harmonize DAST protocols.