Daily Sepsis Research Analysis
Analyzed 43 papers and selected 3 impactful papers.
Summary
Analyzed 43 papers and selected 3 impactful articles.
Selected Articles
1. Dynamic CD177/CD10 ratio for infection diagnosis and mortality risk stratification in critically ill patients: a prospective cohort study.
In a prospective cohort with serial neutrophil phenotyping, the CD177/CD10 ratio outperformed CRP and PCT in differentiating non-septic infection from sepsis (AUC 0.92) and distinguished non-infectious inflammation from infection. Dynamic trajectory subtypes stratified short-term mortality, with a ‘rising’ pattern associated with 62.5% 7-day mortality.
Impact: This study proposes an accessible, mechanism-informed biomarker that improves diagnostic accuracy and real-time risk stratification beyond current standards. It offers a path to integrate functional neutrophil states into sepsis triage and monitoring.
Clinical Implications: The CD177/CD10 ratio could augment ED/ICU triage by distinguishing infection from sterile inflammation and flagging high-risk trajectories early. Implementation requires standardized flow cytometry protocols and multicenter validation before incorporation into sepsis pathways.
Key Findings
- At a cut-off of 6.07, the CD177/CD10 ratio differentiated non-septic infection from sepsis with AUC 0.92, outperforming CRP (0.85) and PCT (0.85).
- The ratio distinguished non-infectious inflammation from infection (AUC 0.79 for NI vs others; AUC 0.71 for NI vs NS-I).
- Dynamic subtyping (rising/declining/stable) stratified 7-day outcomes: rising subtype had 62.5% mortality; declining and stable subtypes had 85% and 92.59% survival, respectively.
- Serial flow cytometry of PMN CD177 and CD10 enabled longitudinal, physiology-linked monitoring.
Methodological Strengths
- Prospective design with serial biomarker measurements and predefined clinical strata
- Head-to-head comparison against CRP and PCT with AUC-based performance metrics
Limitations
- Modest patient sample size and need for multicenter external validation of thresholds
- Flow cytometry-based assay requires standardization and may limit immediate scalability
Future Directions: Conduct multicenter validation with standardized protocols, assess integration into early sepsis bundles, automate gating/analysis, and test impact on clinical decision-making and outcomes.
2. A preclinical randomised controlled dose optimization of megadose sodium ascorbate for reversal of gram-negative sepsis-induced cardiovascular, brain and kidney dysfunction.
In a randomized, controlled ovine model of gram-negative sepsis, only 3.0 g/kg sodium ascorbate (plasma ~10 mmol/L) rapidly restored MAP, halved norepinephrine dependence, and improved renal medullary oxygenation and urine flow, while lower doses were ineffective. Molecular readouts showed reduced renal NF-κB and increased eNOS phosphorylation.
Impact: This study defines a clear therapeutic threshold for megadose vitamin C in established sepsis with multi-organ dysfunction in a large-animal model, directly informing dose selection and mechanistic endpoints for upcoming human trials.
Clinical Implications: Supports testing high-dose sodium ascorbate (targeting plasma ~10 mmol/L) in early-phase human trials with careful safety monitoring. Provides mechanistic and physiologic endpoints (MAP, renal oxygenation) to guide trial design.
Key Findings
- Only 3.0 g/kg sodium ascorbate (plasma ~10 mmol/L) rapidly restored MAP and enabled norepinephrine withdrawal in 50% of animals (P=0.007).
- Dose-dependent improvements in renal medullary oxygenation (from 25.2±3.3 to 43.4±4.5 mmHg) and urine flow (0.5±0.2 to 6.9±2.4 ml/kg/h).
- Renal NF-κB expression decreased (~−53%) and phosphorylated eNOS (Ser-1177) increased (~+220%) at 3.0 g/kg vs vehicle.
- Lower doses (1.0, 2.0 g/kg) did not significantly reduce vasopressor requirements.
Methodological Strengths
- Randomized, controlled dose-ranging in a large-animal sepsis model with invasive physiologic monitoring
- Multi-organ mechanistic readouts linking hemodynamics to molecular signaling
Limitations
- Preclinical animal study with small group sizes (n=7–8/group) and short observation window
- Human safety and efficacy at megadose levels remain to be established
Future Directions: Proceed to phase I/II human dose-finding with pharmacokinetic targeting (~10 mmol/L), organ-specific endpoints, and safety labs (oxalate, electrolytes); explore combination with vasopressor-sparing strategies.
3. SIRT2 Regulates Ex Vivo PBMC Adhesion in Septic Shock Patients.
Septic shock PBMCs exhibited endotoxin and adhesion tolerance with elevated SIRT2, reduced CD18 activation, and impaired transmigration. Ex vivo SIRT2 inhibition with AK-7 restored PBMC adhesion/transmigration and enhanced macrophage phagocytosis, supporting PBMC adhesion as a physiological biomarker of hypo-inflammation and SIRT2 as a therapeutic target.
Impact: Identifies a modifiable immunometabolic driver of sepsis-associated hypo-inflammation in human cells and a physiological biomarker (PBMC adhesion) with potential for patient stratification.
Clinical Implications: PBMC adhesion assays may detect hypo-inflammatory states to guide immunoadjuvant timing; SIRT2 inhibition merits clinical development but requires safety/efficacy trials.
Key Findings
- Septic shock PBMCs showed endotoxin tolerance with muted TNF/IL-1β response and ‘adhesion tolerance’ with reduced adhesion to ICAM-1, decreased CD18 activation, and impaired transmigration.
- SIRT2 expression was elevated in endotoxin-tolerant PBMCs; pharmacologic inhibition with AK-7 restored CD18 activation, adhesion, and transmigration.
- In monocyte-derived macrophages from septic shock patients, AK-7 improved phagocytosis ex vivo.
- PBMC adhesion is proposed as a physiological biomarker for detecting hypo-inflammation in sepsis.
Methodological Strengths
- Use of primary human samples with complementary functional assays (adhesion, transmigration, phagocytosis)
- Pharmacologic modulation (AK-7) provides causal support for SIRT2 involvement
Limitations
- Sample size and detailed cohort characteristics are not specified in the abstract
- Ex vivo findings without in vivo clinical outcomes; single inhibitor used
Future Directions: Validate PBMC adhesion as a biomarker in larger, phenotyped cohorts; develop standardized assays; assess SIRT2 modulation in early-phase clinical trials with immune function endpoints.