Daily Sepsis Research Analysis
Three studies advance sepsis science across the translational spectrum: (1) a multi-omics human-mouse investigation reveals early serine-centered metabolic rewiring that differentiates uncomplicated infection from sepsis; (2) a PROSPERO-registered meta-analysis clarifies the diagnostic value and limits of complete blood count parameters in neonatal sepsis; and (3) a 20-year population-based analysis delineates species shifts, resistance patterns, and sex differences in Candida bloodstream infect
Summary
Three studies advance sepsis science across the translational spectrum: (1) a multi-omics human-mouse investigation reveals early serine-centered metabolic rewiring that differentiates uncomplicated infection from sepsis; (2) a PROSPERO-registered meta-analysis clarifies the diagnostic value and limits of complete blood count parameters in neonatal sepsis; and (3) a 20-year population-based analysis delineates species shifts, resistance patterns, and sex differences in Candida bloodstream infection outcomes.
Research Themes
- Early metabolic biomarkers and mitochondrial pathways in sepsis onset
- Diagnostic accuracy of CBC parameters in neonatal sepsis
- Long-term epidemiology and antifungal resistance in Candida bloodstream infection
Selected Articles
1. Multi-Omics and -Organ Insights into Energy Metabolic Adaptations in Early Sepsis Onset.
This translational study integrates human serum metabolomics/lipidomics with mouse single-nucleus RNA-seq to reveal early serine-centered energy metabolic adaptations that distinguish uncomplicated infection from sepsis. Mitochondrial gene modules (Cox4i1, Cox8a, Ndufa4) are down-regulated across tissues, with liver-specific serine-dependent shifts. Findings suggest feasible early biomarkers and mitochondrial-metabolic targets for risk stratification.
Impact: Bridging presymptomatic human biomarkers with mechanistic in vivo validation advances early sepsis detection and illuminates mitochondrial pathways. It identifies specific metabolites and gene modules with translational potential.
Clinical Implications: Supports development of early risk-stratification assays using serine-centered metabolite panels and suggests evaluating mitochondrial bioenergetic pathways as therapeutic targets, particularly hepatic serine metabolism.
Key Findings
- Untargeted serum metabolomics/lipidomics in 152 presymptomatic surgical patients identified serine and aminoadipic acid as discriminators between postoperative uncomplicated infection and sepsis.
- Single-nucleus RNA-seq in a mouse sepsis model showed tissue-independent down-regulation of serine and energy-related genes with key roles for mitochondrial genes Cox4i1, Cox8a, and Ndufa4.
- Liver-specific serine-dependent metabolic shifts were highlighted, linking systemic metabolite signatures to organ-level energy metabolism.
- Integrative multi-omics across species indicates early bioenergetic failure as a unifying feature preceding sepsis onset.
Methodological Strengths
- Cross-species, multi-omics design integrating human metabolomics/lipidomics with mouse single-nucleus RNA-seq.
- Organ- and pathway-level resolution identifying mitochondrial gene modules linked to systemic metabolites.
Limitations
- Moderate human sample size from a surgical cohort may limit generalizability.
- External validation cohorts and prospective diagnostic performance metrics are needed.
Future Directions: Validate metabolite panels in multicenter cohorts, define predictive thresholds, and test serine/mitochondrial pathway modulation in preclinical and early-phase interventional studies.
2. Population-based longitudinal study over two decades of Candida and Candida-like species bloodstream infection reveals gender and species differences in mortality, recurrence and resistance.
In 2,586 Candida/Candida-like bloodstream infection episodes over 20 years in Queensland, species distributions shifted with overall low antifungal resistance. Thirty-day mortality remained 21%; C. parapsilosis complex was linked to lower mortality, while C. tropicalis trended higher. Recurrence (3.1%) was associated with uncommon species and endovascular sources, and females exhibited higher fluconazole resistance.
Impact: Large-scale, population-based surveillance with rigorous modeling provides actionable insights into species dynamics, resistance, and risk factors that can refine empirical therapy and follow-up strategies.
Clinical Implications: Supports species-aware empiric antifungal choices, closer monitoring for recurrence in patients with uncommon species or endovascular sources, and consideration of sex-specific resistance patterns.
Key Findings
- Across 2,586 Ca-BSI episodes, C. albicans and C. parapsilosis complex declined, while Nakaseomyces glabratus and Candida dubliniensis increased.
- Overall resistance remained low: fluconazole 3.2% and echinocandins 0.7%; fluconazole resistance decreased from 4.5% to 2.2% over time (P<0.01).
- Thirty-day mortality was 21% and unchanged; C. parapsilosis complex associated with reduced mortality (aHR 0.44), while C. tropicalis trended higher (aHR 1.35).
- Recurrence within one year was 3.1%, linked to uncommon species (aSHR 6.60) and endovascular source (aSHR 4.42); males had lower recurrence risk (aSHR 0.57).
- Females exhibited higher fluconazole resistance (4.1% vs 2.4%, P=0.02); resistance was higher in recurrent episodes.
Methodological Strengths
- Population-wide, 20-year surveillance with linkage to clinical, microbiological, and outcome databases.
- Appropriate time-to-event modeling (Cox and Fine-Gray) for mortality and recurrence.
Limitations
- Retrospective design with potential residual confounding and incomplete susceptibility testing (1836/2586 isolates tested).
- Generalizability may be limited outside Queensland or differing healthcare settings.
Future Directions: Enhance prospective, real-time antifungal resistance surveillance, include emerging species (e.g., Candida auris), and evaluate targeted interventions for high-risk recurrence groups.
3. Role of complete blood count in the diagnosis of culture-proven neonatal sepsis: a systematic review and meta-analysis.
This PROSPERO-registered systematic review/meta-analysis found that functional CBC indices, especially ITR (>0.20), offer moderate diagnostic accuracy (sensitivity 66.3%, specificity 85.4%) for culture-proven neonatal sepsis. Mean neutrophil volume is promising, but heterogeneity limits generalization; CBC should augment, not replace, comprehensive sepsis evaluation.
Impact: Clarifies the real-world diagnostic contribution and limits of ubiquitous CBC testing in neonatal sepsis, guiding algorithms and resource-conscious care.
Clinical Implications: Use ITR thresholds (e.g., >0.20) and potentially MNV as adjuncts within sepsis bundles, while avoiding overreliance on CBC alone; standardize cut-offs and sampling timing in protocols.
Key Findings
- ITR >0.20 achieved pooled sensitivity 66.3% and specificity 85.4% for culture-proven neonatal sepsis.
- Mean neutrophil volume showed promising diagnostic utility but with substantial inter-study heterogeneity.
- CBC is rapid and low-volume, suitable as an adjunct rather than a stand-alone diagnostic tool in neonates.
Methodological Strengths
- PROSPERO-registered protocol and comprehensive multi-database search.
- Bias assessment with modified QUADAS-2 and pooled accuracy estimates across CBC parameters.
Limitations
- Substantial heterogeneity across studies, including varying definitions, thresholds, and timing of sampling.
- Potential publication bias and limited standardization of emerging parameters like MNV.
Future Directions: Prospective, standardized diagnostic accuracy studies harmonizing CBC thresholds/timing and integrating CBC with biomarkers (e.g., CRP, PCT) and clinical scores.