Daily Sepsis Research Analysis
Three studies advanced sepsis research across technology, biomarkers, and stewardship. A microfluidic digital ELISA enabled 2-hour, multiplex, 3.5-μL whole-blood cytokine monitoring in mice, predicting organ injury in sepsis. In 51,544 suspected infections, CRP percentile trajectories were modestly linked to antibiotic decisions and strongly to 5–30-day mortality. A prospective cohort tied GSDMD-driven NETs and glycocalyx injury to sepsis-induced coagulopathy and outcomes, highlighting actionabl
Summary
Three studies advanced sepsis research across technology, biomarkers, and stewardship. A microfluidic digital ELISA enabled 2-hour, multiplex, 3.5-μL whole-blood cytokine monitoring in mice, predicting organ injury in sepsis. In 51,544 suspected infections, CRP percentile trajectories were modestly linked to antibiotic decisions and strongly to 5–30-day mortality. A prospective cohort tied GSDMD-driven NETs and glycocalyx injury to sepsis-induced coagulopathy and outcomes, highlighting actionable biomarkers.
Research Themes
- Real-time multiplex biomarker monitoring for sepsis
- CRP dynamics informing antibiotic stewardship and prognosis
- GSDMD-NETs and endothelial glycocalyx injury in sepsis-induced coagulopathy
Selected Articles
1. High-temporal-resolution on-site multiplex biomarker monitoring in small animals using microfluidic digital ELISA.
This study introduces a semi-automated microfluidic digital ELISA that performs multiplex cytokine quantification from 3.5 μL whole blood with a 2-hour turnaround. In a murine sepsis model, early cytokine trajectories correlated with a liver-injury biomarker, enabling prognostication and reducing animal use via serial sampling.
Impact: Methodological innovation enabling real-time, low-volume, multiplex biomarker monitoring can reshape sepsis phenotyping, trial design, and precision therapeutics.
Clinical Implications: While preclinical, the platform paves the way for bedside serial biomarker-guided care in the ICU and for higher-fidelity preclinical testing that better mirrors clinical decision timelines.
Key Findings
- Developed a semi-automated microfluidic digital ELISA enabling multiplex cytokine profiling from 3.5 μL whole blood within 2 hours.
- Achieved precise temporal monitoring of cytokines in a murine sepsis model, with early cytokine levels correlating with a liver-injury biomarker.
- Enabled longitudinal sampling in single animals, substantially reducing animal numbers needed for preclinical studies.
Methodological Strengths
- Single-molecule counting with whole-blood compatibility enabling ultra-low-volume, high-sensitivity, multiplex assays.
- Demonstrated prognostic linkage between early cytokine dynamics and organ injury in a disease-relevant sepsis model.
Limitations
- Preclinical proof-of-concept; no human validation or clinical workflow integration yet.
- Prototype platform; assay menu, throughput, and automation for clinical deployment remain to be established.
Future Directions: Validate in large-animal and human studies, expand multiplex panels (e.g., host-response and endothelial markers), and integrate into ICU decision-support for biomarker-guided therapy.
2. Interplay between C-reactive protein responses and antibiotic prescribing in people with suspected infection.
In 51,544 suspected infection episodes, increases in CRP centiles modestly increased antibiotic escalation and faster-than-expected CRP recovery supported de-escalation, yet most prescribing remained unchanged. Early CRP percentile trajectories were strongly associated with 5–30-day mortality, supporting CRP dynamics as a prognostic marker.
Impact: This large, real-world analysis quantifies how CRP trajectories relate to stewardship decisions and mortality, informing pragmatic integration of CRP dynamics into clinical workflows.
Clinical Implications: Incorporating CRP percentile trajectories may refine escalation/de-escalation decisions and risk stratification, but should supplement—not replace—clinical judgment due to modest effects and testing bias.
Key Findings
- Analyzed 51,544 suspected infection episodes with linked CRP trajectories and prescribing data from 2016–2021.
- Suboptimal recovery (rising CRP centiles) was associated with higher antibiotic escalation (16.5% vs 10.7%), while faster-than-expected recovery supported de-escalation (23.6% vs 17.2%).
- Early CRP percentile changes (days 1–4) were strongly associated with 5–30-day mortality, underscoring prognostic value.
Methodological Strengths
- Very large cohort with detailed serial biomarker and prescribing data.
- Multivariable modeling (multinomial logistic regression, linear mixed models) addressing confounding and temporal dynamics.
Limitations
- Observational design with potential residual confounding and testing bias.
- Single-region UK dataset may limit generalizability; CRP is only one factor in decision-making.
Future Directions: Prospective interventional studies testing CRP-trajectory–guided stewardship, integration with other biomarkers (e.g., PCT, cytokines), and validation across diverse health systems.
3. GSDMD-NETs in patients with sepsis-induced coagulopathy and their interaction with glycocalyx damage.
In a registered prospective ICU cohort (n=70), plasma N-GSDMD and MPO-DNA were elevated in sepsis-induced coagulopathy and correlated with glycocalyx injury markers (syndecan-1, MMP-9). These biomarkers predicted SIC severity and mortality, linking GSDMD-driven NETs to endothelial damage and adverse outcomes.
Impact: Provides mechanistic-clinical linkage between GSDMD-driven NETs, endothelial glycocalyx damage, and coagulopathy in sepsis, identifying measurable biomarkers with prognostic utility.
Clinical Implications: N-GSDMD and MPO-DNA may aid early identification and risk stratification of SIC and inform trials of NET/GSDMD-targeted or glycocalyx-protective therapies.
Key Findings
- Prospective, registered ICU cohort (n=70) showed higher N-GSDMD and MPO-DNA in SIC versus non-SIC patients.
- GSDMD-NETs biomarkers correlated with glycocalyx injury markers (syndecan-1, MMP-9), linking NET formation to endothelial damage.
- N-GSDMD and MPO-DNA predicted SIC severity and mortality by logistic regression and ROC analyses.
Methodological Strengths
- Prospective cohort with trial registration and predefined biomarkers measured by ELISA.
- Multimodal analyses (logistic regression, ROC, correlation) linking biology to outcomes.
Limitations
- Single-center respiratory ICU with modest sample size limits generalizability.
- Observational associations cannot prove causality; timing of sampling vs. disease phase may influence levels.
Future Directions: External validation in larger multicenter cohorts, dynamic sampling to define temporal thresholds, and interventional studies of NET/GSDMD inhibition or glycocalyx-protective strategies.