Sepsis Research Analysis
July’s sepsis literature coalesced around three themes: a systems-level glycoproteomic regulator tied to outcomes, critical gaps in bedside hemodynamic monitoring validation, and a mechanistically novel antimicrobial entry pathway with in vivo efficacy. Work on the mannose receptor Mrc1 linked lectin biology to broad shifts in circulating mannosylated proteins and sepsis mortality, reframing biomarker interpretation. A rigorous meta-analysis challenged reliance on many cardiac output monitors in
Summary
July’s sepsis literature coalesced around three themes: a systems-level glycoproteomic regulator tied to outcomes, critical gaps in bedside hemodynamic monitoring validation, and a mechanistically novel antimicrobial entry pathway with in vivo efficacy. Work on the mannose receptor Mrc1 linked lectin biology to broad shifts in circulating mannosylated proteins and sepsis mortality, reframing biomarker interpretation. A rigorous meta-analysis challenged reliance on many cardiac output monitors in septic shock, urging inclusion of trending and latency metrics. Finally, antimicrobial polymers leveraging transient carbene formation achieved non-lytic intracellular uptake and activity against MDR pathogens in murine sepsis models, opening a translational avenue.
Selected Articles
1. Mrc1 (MMR, CD206) controls the blood proteome in reducing inflammation, age-associated organ dysfunction and mortality in sepsis.
Using glycosidic linkage enrichment in genetic mouse models, this study shows Mrc1 governs the abundance of over 200 circulating mannosylated proteins. Mrc1 dysfunction aligns with inflammatory and organ dysfunction pathways overlapping human sepsis signatures, linking lectin receptor biology to systemic sepsis pathobiology and clarifying glycoprotein biomarker interpretation.
Impact: Reveals a systems-level regulator of the circulating glycoproteome with direct links to sepsis outcomes, bridging mechanistic biology and biomarker/prognostic development.
Clinical Implications: Supports validation of Mrc1 and mannosylated glycoprotein panels in human cohorts for prognostication and encourages exploration of lectin receptor modulation to reduce inflammation and organ failure.
Key Findings
- Mrc1 deficiency causes accumulation of >200 endogenous mannosylated plasma proteins.
- Accumulated proteins map to inflammatory and organ dysfunction pathways overlapping human sepsis signatures.
- Circulating Mrc1 increases during sepsis proportionally to mannosylated protein accumulation.
2. Cardiac output monitors in septic shock: do they deliver what matters? A systematic review and meta-analysis.
A pre-registered meta-analysis of 26 prospective studies (1,323 patients) found a pooled percentage error of 49% across CO monitors (threshold 30%), with calibrated pulse contour analysis meeting acceptable error while many uncalibrated and noninvasive devices performed poorly. Trending ability and time-response were rarely reported, prompting a shift in validation standards.
Impact: Challenges routine reliance on continuous CO devices in septic shock and elevates trending and latency as essential validation metrics for real-time care.
Clinical Implications: Prefer calibrated pulse-contour systems for continuous CO in septic shock; mandate reporting of trending, precision, and time-response in validation studies.
Key Findings
- Pooled percentage error across devices was 49%, exceeding the 30% threshold.
- Calibrated pulse contour analysis achieved acceptable error (25%); uncalibrated PCA, bioimpedance, and bioreactance performed poorly.
- Only a minority of datasets assessed trending, and few reached ≥90% concordance.
3. Carbene formation as a mechanism for efficient intracellular uptake of cationic antimicrobial carbon acid polymers.
Mechanistic preclinical work shows oligoimidazolium carbon-acid polymers transiently form N-heterocyclic carbenes that enable non-lytic membrane translocation, achieving potent activity against colistin- and multidrug-resistant bacteria. Amide derivatives improved outcomes in murine sepsis and infection models, indicating a new class of intracellular-targeting antimicrobials.
Impact: Offers a generalizable, non-lytic uptake mechanism that addresses a key translational barrier for antimicrobial polymers with demonstrated in vivo efficacy against MDR pathogens.
Clinical Implications: Supports development of intracellular-targeting antimicrobials for MDR sepsis pathogens; next steps include PK/PD, toxicity, and dosing studies to enable translation.
Key Findings
- Transient N-heterocyclic carbene formation enables membrane translocation without lysis.
- Carbon-acid OIMs are active against colistin- and multidrug-resistant bacteria.
- OIM amide derivatives improved outcomes in murine sepsis and infection models; polymeric variants showed prophylactic efficacy.