Daily ReportOct 16, 2026
Sepsis, October 16 edition
We read 29 papers and selected 3.
Summary
Today's most impactful sepsis research spans mechanistic target discovery, organ-protective signaling, and implementation of rapid diagnostics. Preclinical studies identified PTPRO and Erbin-related pathways as potential therapeutic targets, while a pediatric before-and-after study showed that FilmArray integration substantially accelerated bacteremia reporting and improved antibiotic adjustment.
Research Themes
- Blood-brain barrier protection and sepsis-associated encephalopathy
- Mitochondrial oxidative stress and inflammasome-mediated organ injury
- Rapid microbiological diagnosis and antibiotic stewardship
Selected Articles
1. A PTPRO inhibitor Pi mitigates endotoxemia-induced encephalopathy-mediated blood-brain barrier disruption through cytoskeletal regulation.
Using endothelial cell systems and an LPS-induced murine encephalopathy model, the study showed that PTPRO promotes blood-brain barrier disruption through F-actin reorganization, stress-fiber formation, and intercellular gap development. Pharmacological inhibition with Pi or genetic PTPRO deficiency reduced barrier leakage through the ErbB2-Rho-MLC2 pathway, with limited effects on inflammatory cytokines.
Impact: This study identifies PTPRO as a previously underrecognized regulator of blood-brain barrier integrity in sepsis-associated encephalopathy and provides pharmacological target-validation evidence. It also separates vascular barrier protection from broad cytokine suppression, suggesting a potentially complementary therapeutic strategy.
Clinical Implications: PTPRO inhibition could become a mechanism-based approach to prevent or reduce blood-brain barrier injury and neurological complications during sepsis. Clinical translation will require confirmation of inhibitor specificity, pharmacokinetics, blood-brain barrier penetration, and safety in clinically relevant sepsis models.
Key Findings
- LPS increased PTPRO expression in brain tissue and cerebral endothelial cells.
- PTPRO promoted F-actin reorganization, stress-fiber formation, and endothelial gap formation.
- Pi treatment or PTPRO deficiency reduced blood-brain barrier leakage through the ErbB2-Rho-MLC2 pathway.
Methodological Strengths
- Convergent genetic and pharmacological experiments were performed across immortalized and primary endothelial cells and an in vivo mouse model.
- Barrier permeability, cytoskeletal remodeling, signaling, and in vivo leakage were assessed using complementary methods.
Limitations
- The study is preclinical and used an LPS endotoxemia model rather than polymicrobial sepsis.
- The abstract does not provide exact animal numbers or establish clinical pharmacology and long-term neurological outcomes.
Future Directions: Future studies should test PTPRO inhibition in polymicrobial sepsis models, define therapeutic timing and dosing, evaluate effects on cognition and survival, and develop selective inhibitors with suitable systemic and central nervous system exposure.
BACKGROUND AND PURPOSE: Septic encephalopathy (SE) is closely associated with disruption of blood-brain barrier (BBB), resulting in neurological deficits and poor clinical outcomes. Protein tyrosine phosphatase receptor type O (PTPRO) regulates disease states by dephosphorylating membrane-associated proteins and modulating intracellular signalling. Here we have examined the role of PTPRO in regulating BBB permeability and have assessed a PTPRO inhibitor (Pi) in mitigating BBB disruption during endotoxemia-associated encephalopathy. EXPERIMENTAL APPROACH: Genetic and pharmacological approaches, including PTPRO overexpression, knockdown or deficiency and Pi treatment, were used to evaluate endothelial dysfunction in bEND.3 cells, primary mouse brain microvascular endothelial cells and an LPS-induced murine model of endotoxemia-associated encephalopathy. Barrier dysfunction, cytoskeletal remodelling and signalling events were assessed using permeability assays, immunoblotting, immunofluorescence and in vivo BBB leakage analyses.
2. Erbin deficiency exacerbates sepsis‑induced liver injury through mitochondrial ROS/NLRP3‑mediated inflammatory responses.
In cecal ligation and puncture mice and LPS/ATP-stimulated macrophages, Erbin deficiency aggravated liver injury, mitochondrial disruption, oxidative stress, NLRP3 inflammasome activation, cytokine production, and pyroptotic responses. MitoQ attenuated the pro-inflammatory and pro-pyroptotic effects, supporting a protective Erbin–mitochondrial ROS–TXNIP/NLRP3 axis in sepsis-induced liver injury.
Impact: The study defines Erbin as an endogenous brake on mitochondrial oxidative stress and inflammasome-driven liver injury in sepsis. Use of knockout mice, macrophage experiments, and mitochondrial ROS scavenging provides a coherent mechanistic framework and a candidate pathway for therapeutic development.
Clinical Implications: The Erbin–TXNIP/NLRP3 pathway may provide a basis for therapies aimed at reducing sepsis-associated liver injury and pyroptosis. However, Erbin-directed interventions and mitochondrial antioxidants require validation for efficacy, timing, tissue selectivity, and effects on host defense.
Key Findings
- Erbin deficiency worsened CLP-induced liver histopathology, mitochondrial disruption, oxidative stress, and inflammatory cytokine production.
- Erbin loss enhanced mitochondrial ROS accumulation and TXNIP–NLRP3 inflammasome signaling.
- MitoQ substantially attenuated the pro-inflammatory and pro-pyroptotic effects of Erbin deficiency in macrophages.
Methodological Strengths
- The mechanism was examined in both a polymicrobial mouse sepsis model and stimulated primary bone marrow-derived macrophages.
- Histology, ultrastructure, biochemical assays, cytokine measurements, gene expression, and protein signaling were evaluated using multiple complementary methods.
Limitations
- The findings are preclinical and do not establish whether Erbin modulation improves survival or organ function in human sepsis.
- The study focuses mainly on macrophage and liver mechanisms, so effects on other immune and organ systems remain uncertain.
Future Directions: Future work should determine whether Erbin augmentation or targeted inhibition of mitochondrial ROS/TXNIP/NLRP3 improves survival in diverse sepsis models, preserves antimicrobial immunity, and remains effective during clinically relevant treatment windows.
Sepsis‑induced liver injury (SLI) is a life‑threatening complication of sepsis characterized by microcirculatory dysfunction, oxidative stress, excessive inflammation, and immune dysregulation. However, the role of ErbB2 interacting protein (Erbin) in SLI remains unclear. In the present study, the functional role and underlying mechanism of Erbin were investigated in a cecal ligation and puncture (CLP)‑induced mouse model of SLI using wild‑type and Erbin‑knockout (Erbin‑/‑) mice, together with lipopolysaccharide (LPS)/adenosine triphosphate (ATP)‑stimulated bone marrow‑derived macrophages (BMDMs). Liver histopathology, mitochondrial ultrastructure, oxidative stress, inflammatory cytokine production, and pyroptosis‑related signaling were assessed using H&E staining, transmission electron microscopy, biochemical assays, ELISA, quantitative PCR, immunohistochemistry, and western blotting. Erbin deficiency markedly aggravated CLP‑induced liver injury, as evidenced by more severe histopathological damage, mitochondrial disruption, oxidative stress, NOD‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, and pro‑inflammatory cytokine production.
3. [Rapid microbiological diagnosis of bacteremia in pediatrics: a quasi-experimental study].
In 173 children with bacteremia, integrating FilmArray into a multidisciplinary antibiotic stewardship program reduced the median microbiological reporting time from 26 hours to 6 hours. Antibiotic adjustment increased from 41% to 55%, and adjustment within 48 hours of blood culture collection increased from 31% to 47%, with reduced empirical meropenem and vancomycin exposure.
Impact: This study demonstrates a practical, system-level intervention that translates rapid molecular microbiology into earlier antibiotic optimization in children with bacteremia. Its direct effect on reporting time and stewardship processes is clinically actionable, even though causal inference is limited by the before-and-after design.
Clinical Implications: Pediatric hospitals may consider integrating FilmArray or comparable rapid blood-culture platforms with multidisciplinary stewardship teams to accelerate targeted antibiotic therapy and reduce unnecessary broad-spectrum exposure. Implementation should include local cost-effectiveness assessment, workflow integration, and monitoring for resistance and safety outcomes.
Key Findings
- The study included 173 children with bacteremia, with 88 in the pre-intervention group and 85 in the post-intervention group.
- Median microbiological reporting time decreased from 26 hours to 6 hours after FilmArray implementation.
- Antibiotic adjustment increased from 41% to 55%, and adjustment within 48 hours increased from 31% to 47%.
Methodological Strengths
- The intervention was evaluated in a real pediatric hospital antibiotic stewardship workflow with clinically relevant process outcomes.
- The pre- and post-intervention groups were reported as comparable, and the study included objective timing and antibiotic-use measures.
Limitations
- The before-and-after design is vulnerable to temporal confounding, secular trends, and changes in clinical staffing or practice.
- The sample was relatively small and the abstract does not establish effects on mortality, length of stay, adverse events, or resistance.
- The study was conducted in a single pediatric hospital, which may limit generalizability.
Future Directions: Multicenter prospective evaluations should assess patient-centered outcomes, cost-effectiveness, antimicrobial resistance, turnaround-time reliability, and subgroup effects according to pathogen and clinical severity. Cluster-randomized implementation studies would provide stronger causal evidence.
INTRODUCTION: Timely treatment of bacteremia is essential to reduce morbidity and mortality. Multidisciplinary collaboration and the use of rapid microbiological diagnostic methods are key to optimizing antibiotic (ATB) use. AIMS: To compare reporting time, clinical outcomes, and antibiotic use in children with bacteremia before and after the integration of FilmArray® (FA) into an antibiotic stewardship program. Materials y methods: A quasi-experimental beforeand- after study was conducted to evaluate the integration of FA into an antibiotic stewardship program. Patients younger than 18 years with bacteremia hospitalized at a pediatric hospital were randomly included. Clinical, microbiological, and antibiotic-related variables were analyzed. Statistical analysis was performed using STATA 16. RESULTS: A total of 173 patients were included: 88 in the pre-intervention period and 85 in the post-intervention period; 58 (57%) were male. The median age was 57 months (IQR: 16-112), and 142 patients (83%) had comorbidities. The groups were comparable. In the post-intervention period, there was a significant increase in the proportion of patients who underwent antibiotic adjustment (41% vs. 55%; p=0.01) and in adjustments made within the first 48 hours after blood culture collection (31% vs. 47%; p=0.02).