Daily ReportOct 24, 2026
Sepsis, October 24 edition
We read 6 papers and selected 3.
Summary
The strongest paper identified a reproducible, trajectory-based stratification of sepsis-associated liver injury using early vital signs, with prognostic differences validated in an external cohort. A longitudinal metabolomics resource provides extensive temporal metabolic data for future biomarker and multi-omics studies, while a structured review summarizes the potential and limitations of extracorporeal kidney support in neonates and infants with severe organ dysfunction.
Research Themes
- Dynamic prognostic stratification in sepsis-associated liver injury
- Longitudinal metabolomics and reusable data resources
- Extracorporeal kidney support in critically ill neonates and infants
Selected Articles
1. Identification and validation of early vital sign trajectory subphenotypes for risk stratification in sepsis-associated liver injury: a multicenter retrospective cohort study.
Using 12-hour vital sign trajectories, the investigators identified four exploratory subphenotypes of sepsis-associated liver injury in 1,159 MIMIC-IV patients and externally validated them in 168 patients. A relatively stable subphenotype was associated with lower adjusted 28-day and 90-day mortality than the highest-risk group, with hazard ratios of 0.74 and 0.76, respectively.
Impact: This study moves prognostic assessment from static measurements toward dynamic physiological phenotyping and demonstrates external reproducibility. It provides a clinically interpretable framework that could support individualized monitoring and future treatment-stratification trials.
Clinical Implications: Early trends in heart rate, blood pressure, respiratory rate, and related vital signs may help identify sepsis-associated liver injury patients at different mortality risks. The approach should be considered prognostic rather than treatment-directing until prospective interventional validation is available.
Key Findings
- A four-cluster solution based on early vital sign trajectories identified clinically distinct exploratory subphenotypes.
- The relatively stable Subphenotype 3 had lower adjusted 28-day mortality than the highest-risk Subphenotype 4, with HR 0.74 (95% CI 0.56-0.97).
- The mortality pattern was also reproduced for 90-day mortality and in an external cohort of 168 patients.
Methodological Strengths
- The study used a large derivation cohort and an independent external validation cohort.
- Trajectory features were clustered using K-means, with candidate cluster solutions assessed by internal metrics and bootstrap stability.
Limitations
- The retrospective design limits causal inference and is susceptible to residual confounding and measurement-related bias.
- The four-cluster solution was exploratory, and its incremental prognostic value and clinical utility require prospective evaluation.
Future Directions: Future studies should prospectively validate the trajectory model across diverse intensive care settings, evaluate automated bedside implementation, and determine whether trajectory-guided interventions improve outcomes.
BACKGROUND: Sepsis-associated liver injury (SALI) is a serious clinical syndrome with heterogeneity in outcome among affected individuals. Physiological changes that are critical to outcome prediction are not considered in the existing system of stratification based on single-point observations. This could compromise the effectiveness of individualized treatment. OBJECTIVE: To develop and validate dynamic clinical subphenotypes of SALI using early vital sign trajectories. METHODS: This retrospective cohort study included 1,159 patients from MIMIC-IV as the derivation cohort and 168 patients from the Second Xiangya Hospital as the external validation cohort. Early vital sign trajectories within 12 h of ICU admission were summarized as trajectory-derived features and clustered using K-means.
2. A longitudinal plasma metabolomics dataset of sepsis-associated liver injury across multiple clinical time points.
This data paper provides an LC-MS longitudinal metabolomics resource based on 88 blood samples collected across multiple clinical time points from healthy controls and patients with sepsis-associated liver injury or sepsis without liver injury. It contains 18,247 high-quality metabolic features and 2,894 annotated metabolites, including nucleotide, lipid, and bile acid pathways, and applies exploratory temporal clustering, network analysis, and regularized regression.
Impact: The dataset addresses a major resource gap in the temporal biology of sepsis-associated liver injury and is explicitly designed for reuse. Its breadth may enable independent biomarker validation, pathway analysis, and integration with transcriptomic or proteomic data.
Clinical Implications: The resource may help identify temporal metabolic signatures for early recognition, phenotyping, and prognostic assessment of sepsis-associated liver injury. It is not itself a validated clinical diagnostic test and requires independent clinical validation.
Key Findings
- The resource contains 88 blood samples collected from healthy controls and sepsis patients with or without liver injury across multiple clinical time points.
- Metabolomic profiling produced 18,247 high-quality metabolic features and 2,894 annotated metabolites.
- The dataset includes information relevant to nucleotide, lipid, and bile acid metabolism and supports temporal clustering, network analysis, and feature selection.
Methodological Strengths
- Longitudinal sampling across clinically relevant time points enables temporal rather than purely cross-sectional analyses.
- The dataset provides high-dimensional feature detection, metabolite annotation, and multiple exploratory analytical approaches to facilitate reuse.
Limitations
- The sample size is modest, with 88 total blood samples, which may limit statistical power and generalizability.
- The analyses are exploratory and the identified metabolic signatures have not been independently validated as biomarkers.
Future Directions: Future work should expand the dataset across institutions and disease severities, standardize sampling and preprocessing, and validate candidate metabolites in prospective cohorts with clinically defined outcomes.
Sepsis-associated liver injury is a severe complication of sepsis characterized by substantial metabolic alterations, yet longitudinal metabolomics resources for this condition remain limited. Here, we present an LC-MS-based longitudinal metabolomics dataset comprising 88 blood samples collected from healthy controls and sepsis patients with or without liver injury across multiple ICU-associated clinical time points. Comprehensive metabolomic profiling generated 18,247 high-quality metabolic features and 2,894 annotated metabolites, providing a resource for investigating temporal metabolite patterns with annotations related to nucleotide, lipid, and bile acid metabolism across clinical groups and sampling time points.
3. Extracorporeal kidney support in neonates and infants: therapeutic perspectives and outcomes in multiple organ dysfunction syndrome-a structured narrative review.
This structured narrative review examined hemodiafiltration and continuous kidney replacement therapy in neonates and infants weighing up to 8 kg with multiple organ dysfunction syndrome, sepsis, hyperammonemia, or acute kidney injury. Available reports suggest possible metabolic, acid-base, electrolyte, and hemodynamic stabilization, but the evidence is heterogeneous and predominantly derived from observational studies and case series, with complications including hypotension, circuit clotting, and coagulation abnormalities.
Impact: The review addresses a technically difficult and high-risk population for whom evidence-based extracorporeal support guidance is limited. Its balanced synthesis emphasizes potential benefits while preventing overinterpretation of case-based observations and identifies priorities for multicenter prospective research.
Clinical Implications: Hemodiafiltration may be considered in selected neonates and infants with severe metabolic derangements or organ dysfunction when conventional support is inadequate, but use should occur in experienced centers with careful monitoring of hemodynamics, vascular access, circuit function, and coagulation. The review does not establish a standard indication or superiority over other kidney replacement strategies.
Key Findings
- Hemodiafiltration may support metabolic stabilization, correction of acid-base disturbances, and electrolyte balance in selected neonates and infants.
- Some case-based reports describe hemodynamic stabilization and reduced vasopressor support after extracorporeal therapy, but causality cannot be established.
- Reported complications include hypotension, circuit clotting, and coagulation abnormalities, with substantial variation across studies.
Methodological Strengths
- The review used multiple bibliographic databases and structured search elements covering recent and landmark literature.
- It explicitly considered technical aspects, safety, clinical indications, and limitations across heterogeneous neonatal and infant populations.
Limitations
- The evidence synthesis is descriptive rather than quantitative because of substantial heterogeneity in study designs, populations, protocols, and outcomes.
- Most available evidence comes from observational studies and case series, creating substantial risk of selection bias and confounding.
Future Directions: Prospective multicenter registries and comparative studies should define patient selection, timing, dose, anticoagulation, vascular access, circuit configuration, and short- and long-term outcomes of extracorporeal support in this population.
BACKGROUND: Multiple organ dysfunction syndrome (MODS) remains a major challenge in the intensive care of neonates and infants and is associated with substantial morbidity and mortality, particularly in the presence of sepsis and acute kidney injury. Conventional kidney replacement and detoxification strategies may be difficult to implement in neonates and low-weight infants because of technical and physiological limitations. Hemodiafiltration (HDF), which combines convective and diffusive clearance mechanisms, has emerged as a potential extracorporeal support modality for metabolic and inflammatory control while maintaining hemodynamic stability. OBJECTIVE: To provide a structured narrative review of the available literature on the clinical applications, potential benefits, safety considerations, and technical aspects of hemodiafiltration in neonates and infants with multiple organ dysfunction syndrome.