Daily Sepsis Research Analysis
Analyzed 7 papers and selected 3 impactful papers.
Summary
Across sepsis research today: a multicentre prospective ED study found presepsin offers only modest diagnostic accuracy but may support early risk stratification; a preclinical study shows Bruceine A attenuates sepsis-associated lung injury by promoting M2 macrophage polarization and inhibiting NF-κB; and a small randomized study suggests adjunct vitamin C improves hemodynamics and inflammation in septic shock while a composite biomarker panel shows strong prognostic performance.
Research Themes
- Early diagnosis and risk stratification in sepsis
- Immunomodulatory mechanisms in sepsis-associated lung injury
- Adjunctive therapies and prognostic biomarkers in septic shock
Selected Articles
1. Presepsin for sepsis diagnosis in emergency departments: a multicentre study.
In eight Thai EDs, presepsin modestly outperformed PCT for identifying Sepsis-3 sepsis and septic shock and declined over time. Higher presepsin and PCT were associated with increased 30-day mortality, suggesting presepsin may aid early risk stratification when used alongside clinical assessment.
Impact: A multicentre prospective diagnostic study directly comparing presepsin with PCT under Sepsis-3 provides practice-relevant evidence for ED triage and early management.
Clinical Implications: Use presepsin alongside clinical assessment and routine labs to support early risk stratification and decisions on resuscitation and antibiotics; it should not replace clinical judgment due to modest accuracy.
Key Findings
- Presepsin showed AUROC 0.63 for sepsis and 0.73 for septic shock, slightly higher than PCT.
- Presepsin and PCT levels were higher at ED admission in Sepsis-3 cases and decreased over time.
- Elevated presepsin (OR 2.61) and PCT (OR 1.62) were associated with higher 30-day mortality.
Methodological Strengths
- Multicentre prospective cohort across eight EDs
- Sepsis-3 adjudication and head-to-head comparison with PCT
- Serial biomarker measurements at days 0, 3, and 7 with 30-day mortality follow-up
Limitations
- Overall diagnostic accuracy was modest (AUROC near 0.6 for sepsis)
- Conducted in EDs across a single country, which may limit generalizability
Future Directions: Externally validate presepsin cutoffs and integrate with clinical scores to improve ED triage; evaluate cost-effectiveness and impact on patient-centered outcomes.
OBJECTIVES: To evaluate the diagnostic accuracy of presepsin and procalcitonin (PCT) for sepsis and septic shock (Sepsis-3) in the emergency department (ED) based on the Sepsis-3 definition, where early diagnosis remains challenging due to the lack of rapid and reliable diagnostic methods. METHODS: This multicentre prospective cohort study recruited adults from eight EDs in Thailand between October 2020 and June 2022. Patients with suspected infection or those who met the quick Sequential Organ Failure Assessment criteria were enrolled. Admission blood samples were analysed for presepsin, PCT, lactate and blood culture, with follow-up presepsin and PCT measurements performed on days 3 and 7, and follow-up for 30-day mortality. Sepsis diagnosis was adjudicated with reference to the Sepsis-3 criteria and blood culture result. Diagnostic accuracy metrics, including the area under the receiver operating characteristics curve (AUROCs), sensitivity, specificity and predictive values of presepsin and PCT were evaluated. RESULTS: Of 668 included participants, 438 (65.6%) were diagnosed with sepsis and 58 (8.7%) with septic shock. Presepsin levels were significantly higher in patients with Sepsis-3 than in patients without sepsis at ED admission and decreased over time. Presepsin exhibited a slightly higher AUROC for predicting sepsis (AUROC 0.63 (95% CI 0.59 to 0.67)) and septic shock (AUROC 0.73 (95% CI 0.66 to 0.80)) compared with PCT (AUROC for sepsis 0.62, 95% CI 0.58 to 0.66 and septic shock 0.72, 95% CI 0.65 to 0.78). Elevated presepsin and PCT levels were associated with increased mortality within 30 days (OR 2.61, 95% CI 1.73 to 3.92 and OR of 1.62, 95% CI 1.09 to 2.42 consequently). CONCLUSIONS: Presepsin showed slightly higher diagnostic accuracy than PCT, but overall diagnostic accuracy was modest. When interpreted together with clinical assessment and routine tests, presepsin may assist early risk stratification and support, rather than replace, clinical judgement in decisions such as resuscitation or antibiotic initiation.
2. Bruceine A alleviates lung injury in sepsis-associated acute respiratory distress syndrome by modulating macrophage polarization and NF-κB pathway activity.
In an LPS-induced murine ARDS model, Bruceine A reduced lung edema, tissue injury, and apoptosis; lowered TNF-α/IL-6/IL-1β while increasing IL-10; shifted macrophages toward M2; and inhibited NF-κB activation. Effects were comparable to dexamethasone, indicating a potential natural immunomodulator for sepsis-associated ARDS.
Impact: This study identifies a mechanistic pathway—M2 polarization and NF-κB inhibition—by which a natural compound reduces sepsis-related lung injury, offering a novel therapeutic avenue.
Clinical Implications: While preclinical, the data support further development of Bruceine A or related agents as immunomodulators for inflammatory lung diseases, including sepsis-associated ARDS.
Key Findings
- Bruceine A reduced LPS-induced lung edema, tissue damage, and alveolar apoptosis.
- Proinflammatory cytokines (TNF-α, IL-6, IL-1β) decreased while IL-10 increased with BA.
- BA shifted macrophage polarization from M1 to M2 and inhibited NF-κB activation (↓p-p65, restored IκBα), with effects comparable to dexamethasone.
Methodological Strengths
- Randomized allocation into four well-defined groups including an active comparator (dexamethasone)
- Integrated morphological, biochemical, and molecular readouts (histology, ELISA, IHC, Western blot)
- Consistent effects across multiple markers of injury and inflammation
Limitations
- LPS-induced ARDS in mice may not fully recapitulate human sepsis pathophysiology
- No reported survival outcomes or dose–response/PK data to inform translation
Future Directions: Define dose–response and pharmacokinetics, test in additional sepsis models and human primary cells, and assess safety/efficacy in translational studies.
BACKGROUND: Sepsis-associated acute respiratory distress syndrome (ARDS) is a severe inflammatory lung disorder with high mortality. Bruceine A (BA), a quassinoid from Brucea javanica, exhibits anti-inflammatory and immunomodulatory activities, but its role in ARDS is unclear. OBJECTIVES: This study evaluated the protective effects of BA in lipopolysaccharide (LPS)-induced ARDS and explored its underlying mechanisms. METHODS: Thirty-six C57BL/6 mice were randomized into four groups: Control, LPS, LPS+BA and LPS+dexamethasone (Dex). Lung injury was assessed by histopathology, wet/dry weight ratio and TUNEL assay. Cytokine levels (TNF-α, IL-6, IL-1β, IL-10) were measured by ELISA. Macrophage polarization markers (iNOS, COX-2, Arg-1, YM1, CD206) and NF-κB pathway proteins were evaluated using immunohistochemistry and Western blotting. RESULTS: BA significantly alleviated LPS-induced lung injury, reducing edema, tissue damage and alveolar apoptosis. It suppressed proinflammatory cytokines while enhancing IL-10. BA shifted macrophage polarization from proinflammatory M1 toward anti-inflammatory M2 phenotypes. Furthermore, BA inhibited NF-κB activation, evidenced by reduced phosphorylated p65 and restored IκBα levels. These effects were comparable to Dex. CONCLUSION: BA protects against LPS-induced ARDS in mice by modulating cytokine release, promoting M2 macrophage polarization and suppressing NF-κB activation. These findings suggest BA as a promising natural immunomodulatory agent for inflammatory lung diseases.
3. Prognostic value of T-lymphocyte subsets, lymphocyte-to-high-density lipoprotein ratio, interleukin 6, C-reactive protein and procalcitonin in patients with septic shock and effects of vitamin C on patients with septic shock.
Among 110 septic shock patients, a composite panel (LHR, IL-6, CRP, PCT, CD4+/CD8+) achieved high prognostic accuracy (AUC 0.960). In a randomized comparison, hydrocortisone plus vitamin C led to greater improvements in MAP/CVP, lower HR, and larger reductions in PCT, TNF-α, IL-6, and SOFA than hydrocortisone alone.
Impact: Provides both a high-performing prognostic biomarker combination and randomized evidence suggesting vitamin C may enhance hemodynamics and reduce inflammation in septic shock.
Clinical Implications: The biomarker panel could inform early risk stratification, and adjunct vitamin C may be considered for further study; current evidence is preliminary and should not change practice without larger trials.
Key Findings
- Composite of LHR, IL-6, CRP, PCT, and CD4+/CD8+ predicted 28-day death with AUC 0.960, outperforming single markers.
- Hydrocortisone plus vitamin C improved MAP and CVP more than hydrocortisone alone and reduced HR.
- Vitamin C adjunct led to larger decreases in PCT, TNF-α, IL-6, and SOFA scores compared with control.
Methodological Strengths
- Randomized allocation to adjunct vitamin C vs control on top of hydrocortisone
- Multiple objective endpoints (hemodynamics, inflammatory markers, SOFA) and 28-day outcome stratification
- ROC analysis demonstrating additive prognostic value of a composite biomarker panel
Limitations
- Small sample size and no details on blinding or trial registration
- Single study without external validation of the biomarker panel raises risk of overfitting
Future Directions: Conduct adequately powered, blinded RCTs of vitamin C in septic shock and externally validate the composite biomarker panel in diverse cohorts.
BACKGROUND: Septic shock remains a critical condition with high mortality, necessitating reliable prognostic biomarkers and effective adjunct therapies. OBJECTIVES: This study explored prognostic biomarkers and the effect of vitamin C in septic shock. METHODS: This study analyzed 110 patients (January 2023-March 2024), stratified by 28-day outcome into survival (n=90) and death (n=20) groups. Compared to survivors, the death group exhibited significantly lower lymphocyte-to-high-density lipoprotein ratio (LHR), CD3+, CD3+CD4+, CD4+/CD8+ and higher interleukin 6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), CD3+CD8+. RESULTS: The receiver operating characteristic analysis showed the combination of LHR, IL-6, CRP, PCT and CD4+/CD8+ predicted death best [area under the receiver operating characteristic curve (AUC) =0.960], outperforming single markers. Patients were randomized to control (hydrocortisone) or observation (hydrocortisone with vitamin C) group. Post-treatment, both groups showed improved mean arterial pressure (MAP), central venous pressure (CVP) (increased), heart rate (HR) (decreased) and reduced PCT, tumor necrosis factor-α (TNF-α), IL-6 and Sequential Organ Failure Assessment (SOFA) score; however, improvements were significantly greater in the vitamin C group. CONCLUSION: The combination of LHR, IL-6, CRP, PCT and CD4+/CD8+ has prognostic value. Vitamin C adjunct therapy significantly enhances hemodynamic improvement, reduces inflammation, lowers SOFA scores and improves prognosis in septic shock patients.