Daily Sepsis Research Analysis
Analyzed 10 papers and selected 3 impactful papers.
Summary
Analyzed 10 papers and selected 3 impactful articles.
Selected Articles
1. Sphingosine-1-phosphate regulates platelet fibrinogen binding via sphingosine-1-phosphate receptor type 4.
Using a murine peritonitis model, the study links S1P–S1PR4 signaling to platelet hyperfibrinogenemia, disorganized thrombus formation, and increased DIC incidence. S1PR4 deficiency shortened clotting time and increased clot firmness, suggesting S1PR4 as a brake on sepsis-associated coagulopathy.
Impact: Identifies a receptor-specific mechanism linking lipid signaling to sepsis coagulopathy, pointing to S1PR4 as a potential therapeutic target for DIC.
Clinical Implications: Targeting S1PR4 signaling could modulate platelet-fibrinogen interactions and mitigate coagulopathy in sepsis, warranting translational studies to assess safety and efficacy.
Key Findings
- S1PR4-deficient mice in the CASP sepsis model exhibited increased DIC incidence.
- Platelets lacking S1PR4 showed excessive fibrinogen binding and disorganized thrombus formation versus wild-type.
- Rotational thromboelastometry indicated shortened clotting time and increased clot size in S1PR4 deficiency, consistent with hypercoagulability.
Methodological Strengths
- Use of an established in vivo sepsis model (CASP) with genetic knockout controls
- Convergent functional assays including platelet binding studies and thromboelastometry
Limitations
- Preclinical murine study; human validation is lacking
- Incomplete mechanistic mapping of downstream signaling pathways beyond S1PR4
Future Directions: Test pharmacologic S1PR4 modulators in sepsis models and validate platelet S1PR4 function and biomarkers in human sepsis and DIC cohorts.
INTRODUCTION: Sphingosine-1-phosphate (S1P) is a bioactive signalling sphingolipid secreted by platelets during activation. Platelets express distinct S1P receptors on their surface, and a comprehensive understanding of their effects is yet to be achieved. Here, we describe the regulation of fibrinogen binding in activated platelets via S1P receptor type 4 (S1PR METHODS: Thrombus formation and platelet function in an S1pr RESULTS: In the Colon Ascendens Stent Peritonitis (CASP) model, an increased incidence of disseminated intravascular coagulation (DIC) was observed in S1PR4-deficient mice. Murine platelets from S1PR4-deficient mice showed excessive fibrinogen binding and disorganised thrombus formation compared to wild-type platelets. Rotational thromboelastometry confirmed this result, showing a shortened clotting time and an increased clot size in S1PR CONCLUSION: These findings strongly suggest that S1P signalling via S1PR
2. Analysis and comparison of the difference between two major blood culture system in the laboratory and neonatal intensive care unit.
Across in vitro, prospective NICU cohort, and head-to-head phases, VersaTREK showed higher yield at low bacterial loads and comparable overall performance to BD, with the notable ability to detect from as little as 0.1 mL of blood. These features are advantageous for ELBW infants where blood volume is limited.
Impact: Provides practical, methodologically diverse evidence supporting a blood culture platform suitable for minimal-volume neonatal sampling.
Clinical Implications: In NICUs, choosing systems capable of anaerobic culture and micro-volume detection (e.g., VersaTREK) may improve pathogen recovery in suspected neonatal sepsis, especially when only 0.1 mL can be drawn.
Key Findings
- In vitro testing showed VersaTREK outperformed BD at low bacterial loads.
- Prospective NICU cohort data indicated higher yield with VersaTREK, especially for Gram-positive cocci and Gram-negative bacteria.
- Head-to-head comparison demonstrated comparable overall performance, with VersaTREK detecting from as little as 0.1 mL.
Methodological Strengths
- Three-phase design integrating in vitro, prospective observational, and head-to-head comparisons
- Evaluation of anaerobic and aerobic culture media relevant to neonatal pathogens
Limitations
- Sample sizes and multicenter generalizability are not specified
- Nonrandomized comparisons may be influenced by selection and spectrum bias
Future Directions: Conduct multicenter, adequately powered studies to confirm micro-volume performance and clinical impact on time-to-positivity and antibiotic stewardship.
BACKGROUND: Neonatal sepsis is a critical health concern that demands accurate and timely diagnosis. Blood culture, the gold standard, is challenging in extremely low birth weight (ELBW) infants because of the limited blood volume and potential aerobic culture limitations. The VersaTREK (Thermo Fisher Scientific, Waltham, MA, USA) blood culture system, which requires less blood and offers both aerobic and anaerobic cultures, presents a potential solution. This study aimed to compare the diagnostic performance with the widely used BD (Becton Dickinson, Franklin Lakes, NJ, USA) blood culture systems for neonatal sepsis patients. METHODS: We conducted a three-step study, including in vitro testing of common pathogens, prospective observational cohort data from a neonatal intensive care unit (NICU), and a head-to-head comparison. VersaTREK's blood culture bottles include aerobic and anaerobic media, whereas BD uses a specialized bottle for aerobic cultures. RESULTS: In phase 1 of this in vitro comparison study, VersaTREK outperformed BD, particularly at low bacterial loads. In phase 2, a prospective observational cohort analysis revealed a significantly greater yield with VersaTREK, especially for gram-positive cocci and gram-negative bacteria. In phase 3, a head-to-head comparison demonstrated comparable performance between the two systems, with potential advantages for VersaTREK in scenarios involving minimal blood volumes, as little as 0.1 mL. CONCLUSIONS: The VersaTREK and BD blood culture systems demonstrated similar diagnostic performance, with VersaTREK capable of detecting as little as 0.1 mL of blood. While this is promising in scenarios with minimal blood volume, further investigations with larger sample sizes are needed.
3. The impact of urine output trajectory on clinical outcomes in female patients with genitourinary infections in the intensive care unit.
Among 1,289 ICU females with genitourinary infections, early 3-day urine output trajectories stratified risk: persistently low or declining urine predicted higher 28-day mortality (HR 4.329 and 3.477 vs low-to-high) and more AKI. Dynamic trajectory analysis adds prognostic information beyond static urine volumes.
Impact: Introduces a dynamic, trajectory-based biomarker for early risk stratification in infections prone to sepsis and AKI, enabling timely interventions.
Clinical Implications: Incorporating early urine output trajectories into ICU risk models may improve triage, monitoring intensity, and nephroprotective strategies in female patients with genitourinary infections.
Key Findings
- Four distinct urine output trajectories were identified in the first 3 ICU days: persistently low (65.7%), high-to-low (13.7%), persistently high (4.0%), and low-to-high (16.7%).
- Compared with the low-to-high group, 28-day mortality risk increased in a graded fashion: HR 4.329 (persistently low), 3.477 (high-to-low), and 2.081 (persistently high).
- Persistently low urine output also correlated with a higher incidence of acute kidney injury.
Methodological Strengths
- Latent class growth modeling to capture dynamic physiologic trajectories
- Multivariable adjustment to control confounding in a sizable ICU cohort
Limitations
- Retrospective single-condition (female GU infections) design limits generalizability
- Potential residual confounding and lack of external validation
Future Directions: Prospective multicenter validation and interventional studies testing trajectory-guided care pathways to reduce mortality and AKI.
Genitourinary infections are common in female intensive care unit patients and are associated with acute kidney injury and sepsis, often becoming life-threatening. Although urine volume correlates with these adverse outcomes, the prognostic value of dynamic urine output trajectories remains unclear. This study investigates the relationship between early urine output trajectories and clinical outcomes in female with genitourinary infections. A retrospective cohort of 1289 patients were analyzed. Latent class growth modeling identified distinct urine output trajectories in the first 3 days after intensive care unit admission. The primary endpoint was 28-day mortality, and the secondary outcome was the incidence of acute kidney injury. Four trajectory classes were identified: Class 1-persistently low (65.7%), Class 2-high-to-low (13.7%), Class 3-persistently high (4.0%), and Class 4-low-to-high (16.7%). In multivariable analysis, compared to Class 4, the 28-day mortality risk showed a graded increase with hazard ratio of 4.329 for Class 1, 3.477 for Class 2, and 2.081 for Class 3. Additionally, Class 1 was associated with a significantly higher incidence of acute kidney injury compared to Class 4. The trajectory of urine output changes in female patients with genitourinary infections is a potential variable in predicting mortality and acute kidney injury outcomes.