Daily Sepsis Research Analysis
Analyzed 12 papers and selected 3 impactful papers.
Summary
Analyzed 12 papers and selected 3 impactful articles.
Selected Articles
1. Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification.
This mechanistic study shows that intracellular lactic acidification promotes NLRP3 inflammasome activation and ASC speck formation, while extracellular alkalinization blocks activation. Remarkably, lactic acid directly cleaves pro-IL-1β at the canonical Asp116 site and worsens survival and inflammation in a murine sepsis (CLP) model.
Impact: Identifies intracellular acidification by lactic acid as a driver of inflammasome signaling and cytokine maturation, offering a new mechanistic link between metabolic stress and hyperinflammation in sepsis.
Clinical Implications: Findings caution against exacerbating lactic acidosis and support exploring pH modulation or NLRP3/PKR-targeted strategies in sepsis. They also motivate clinical correlation of lactate levels with IL-1β activity and evaluation of alkalinizing interventions.
Key Findings
- Nigericin/ATP stimulation increased lactic acid production and efflux, leading to intracellular acidification that promoted NLRP3 activation.
- Elevated extracellular lactate impaired efflux, amplifying ASC specks, caspase-1 activation, and IL-1β secretion; extracellular alkalinization abrogated activation.
- Intracellular acidification induced mitochondrial dysfunction, ROS generation, and PKR phosphorylation, facilitating PKR–NLRP3 interaction.
- Lactic acid directly cleaved pro-IL-1β and pro-IL-18, including pro-IL-1β at Asp116, mimicking caspase-1 specificity.
- Systemic lactate administration in CLP sepsis increased IL-1β, neutrophil infiltration, hypothermia, and mortality.
Methodological Strengths
- Integrated in vitro macrophage assays with in vivo CLP sepsis model
- Mechanistic dissection including pH manipulation, mitochondrial/ROS assessments, and PKR–NLRP3 interaction
- Proteomic mapping of lactic acid-mediated cytokine cleavage sites
Limitations
- Preclinical models; absence of human patient validation
- Systemic lactate dosing and pH modulation may not fully recapitulate clinical lactic acidosis dynamics
Future Directions: Correlate lactate and IL-1β activity in patients, test alkalinization or NLRP3/PKR inhibitors in sepsis models, and evaluate safety/efficacy in early-phase clinical trials.
Glycolysis is critical for NLRP3 inflammasome activation, yet the link between lactic acid metabolism and inflammasome signaling remains unclear. Here, we show that stimulation of macrophages with the NLRP3 activators nigericin or ATP induces lactic acid production and efflux via a lactate dehydrogenase-dependent pathway. Accumulation of intracellular lactic acid leads to cytoplasmic acidification, which promotes NLRP3 inflammasome activation. Concurrently, elevated extracellular lactic ac
2. Real-Life Evaluation of Supplemental Anaerobic Blood Culture Bottles in the Virtuo System: Impact on Diagnosis and Therapeutic Management of Patients with Suspected Sepsis.
In 565 suspected sepsis episodes, 16.7% of pathogens were recovered exclusively from anaerobic bottles, prompting antimicrobial changes in 50.5% of those cases, with no time-to-positivity penalty. Routine inclusion of anaerobic bottles increased overall pathogen recovery without higher contamination.
Impact: Provides real-world evidence that adding anaerobic bottles materially enhances diagnostic yield and influences therapy, supporting protocol-level changes in blood culture practices for sepsis workups.
Clinical Implications: Adopt routine paired aerobic–anaerobic blood culture sets in adults with suspected sepsis to improve pathogen recovery and enable timely antimicrobial optimization without delaying detection.
Key Findings
- Of 498 pathogenic microorganisms, 16.7% were isolated only in anaerobic bottles, 26.9% only in aerobic, and 56.4% in both.
- Time to positivity did not differ between aerobic and anaerobic bottles (p > 0.05).
- Therapy was modified in 50.5% of patients with exclusive anaerobic isolates.
- Most exclusive anaerobic-bottle isolates were facultative anaerobes.
- Routine anaerobic bottle use did not increase contamination rates.
Methodological Strengths
- Prospective real-life workflow using BACT/Alert VIRTUO and MALDI-TOF identification
- Paired aerobic–anaerobic sets per patient enabling within-episode comparisons
Limitations
- Single diagnostic platform and adult-weight cohort limit generalizability
- Observational design; no randomized allocation or assessment of patient-centered outcomes beyond therapy modification
Future Directions: Validate across platforms and populations, quantify impact on time-to-appropriate therapy and clinical outcomes, and perform cost-effectiveness analyses.
OBJECTIVE: To evaluate the impact of the systematic inclusion of anaerobic blood culture bottles, in conjunction with aerobic bottles, in the diagnosis and management of patients with suspected sepsis, analyzing their effect on pathogen detection, time to positivity, and subsequent therapeutic modifications. METHODS: A cross-sectional observational study was conducted involving 565 patients weighing 36 kg or more with suspected bacteremia or fungemia. Two sets of blood culture bottles were colle
3. Diagnostic and Prognostic Value of LAMB2 in Sepsis Patients Admitted to the Intensive Care Unit.
In 172 ICU sepsis patients versus 39 controls, LAMB2 levels were significantly lower in septic shock and inversely correlated with lactate, SOFA, creatinine, and BUN. Serum LAMB2 predicted 28-day mortality with an AUC of 0.676, suggesting potential utility as a severity and mortality biomarker.
Impact: Introduces LAMB2, a basement membrane component, as a novel biomarker linked to sepsis severity and mortality, bridging extracellular matrix biology and critical illness.
Clinical Implications: Serum LAMB2 could complement existing scores and biomarkers for early risk stratification in sepsis, though moderate discrimination indicates it should be used within a multimarker panel.
Key Findings
- LAMB2 mRNA and serum levels were significantly lower in septic shock than in sepsis and healthy controls (p < 0.001).
- Serum LAMB2 strongly inversely correlated with lactate (r = -0.823), and LAMB2 mRNA inversely correlated with SOFA, creatinine, and BUN.
- Serum LAMB2 predicted 28-day mortality with AUC 0.676; LAMB2 mRNA AUC was 0.613.
- Baseline immune cell LAMB2 expression was profiled using the Human Protein Atlas dataset.
Methodological Strengths
- Combined serum protein (ELISA) and monocyte mRNA (RT-qPCR) measurements
- Multivariate analyses with ROC and Kaplan–Meier survival assessment
Limitations
- Single-center cohort with modest sample size; external validation not reported
- Predictive performance is moderate; observational design precludes causal inference
Future Directions: External validation in multicenter cohorts, integration into multimarker panels, and mechanistic studies probing how LAMB2 relates to endothelial/organ dysfunction in sepsis.
OBJECTIVE: Sepsis is a major cause of mortality in intensive care unit (ICU) patients. The LAMB2 gene encodes laminin β2, a critical basement membrane component involved in maintaining tissue and organ integrity. However, the clinical significance of LAMB2 expression in sepsis diagnosis and prognosis remains unclear. This study aimed to evaluate the potential of LAMB2 as a biomarker for sepsis. METHODS: A total of 172 sepsis patients admitted to the ICU of the First Affiliated Hospital of Anhui