Daily Sepsis Research Analysis
Three studies advance sepsis science and care: a consensus Core Outcome Set for neonatal sepsis to standardize trials, a multicenter prospective cohort defining four post-sepsis survivor phenotypes with distinct recovery and mortality trajectories, and a large real-world cohort mapping sepsis-associated acute kidney disease (SA-AKD) trajectories with risks of dialysis, mortality, and new CKD. Together, they enable comparable research, risk stratification, and targeted follow-up.
Summary
Three studies advance sepsis science and care: a consensus Core Outcome Set for neonatal sepsis to standardize trials, a multicenter prospective cohort defining four post-sepsis survivor phenotypes with distinct recovery and mortality trajectories, and a large real-world cohort mapping sepsis-associated acute kidney disease (SA-AKD) trajectories with risks of dialysis, mortality, and new CKD. Together, they enable comparable research, risk stratification, and targeted follow-up.
Research Themes
- Standardizing outcomes in neonatal sepsis trials
- Phenotyping post-sepsis trajectories and PICS
- AKI-to-AKD-to-CKD progression after sepsis
Selected Articles
1. Proposed Core Outcomes After Neonatal Sepsis: A Consensus Statement.
An international, multi-stakeholder process produced a 9-item Core Outcome Set for neonatal sepsis research, addressing heterogeneity in trial endpoints. The COS spans mortality, organ support, neurological injury, infection control, multi-organ dysfunction, neurodevelopment, and parental quality of life.
Impact: Establishing a COS enables comparability across trials and strengthens evidence synthesis, accelerating progress in neonatal sepsis therapeutics.
Clinical Implications: Future neonatal sepsis trials should incorporate this 9-outcome COS to improve consistency, facilitate meta-analyses, and ensure patient- and family-centered endpoints.
Key Findings
- Four-stage process (systematic review, real-time Delphi, consensus meetings, dissemination) across global stakeholders
- 306 participants identified 55 candidate outcomes; final COS includes 9 outcomes with ≥80% agreement
- COS items: all-cause mortality, need for mechanical ventilation, brain injury on imaging, neurologic status at discharge, antimicrobial escalation, CNS infections, multiorgan dysfunction, neurodevelopmental impairment, parental quality of life
Methodological Strengths
- Systematic review informing a stakeholder-driven real-time Delphi
- Predefined consensus threshold (≥80%) across diverse international participants
Limitations
- Consensus methods do not establish measurement instruments or timing
- Potential selection bias in stakeholder participation and geographic representation
Future Directions: Develop standardized, validated instruments and timing for each COS item and promote adoption in registries and trial protocols.
2. Phenotypes of Functional Decline or Recovery in Sepsis ICU Survivors: Insights From a 1-Year Follow-Up Multicenter Cohort Analysis.
In 220 sepsis ICU survivors across 21 ICUs, four PICS phenotypes were identified at discharge with distinct 12-month trajectories. Mild PICS improved by 3 months, whereas moderate/severe PICS disabilities persisted and were associated with reduced QoL, low employment, and declining survival in the most severe group.
Impact: Phenotype-based trajectories enable targeted rehabilitation and follow-up pathways, informing resource allocation and trial stratification in post-sepsis care.
Clinical Implications: Use discharge assessments (Barthel Index, cognitive and psychiatric scales, EQ-5D) to phenotype PICS and prioritize intensive rehabilitation for moderate/severe groups with persistent deficits.
Key Findings
- Four PICS phenotypes at discharge: none (n=62), mild physical/cognitive (n=55), moderate all domains (n=53), severe all domains (n=50)
- Mild PICS improved by 3 months; moderate/severe PICS disabilities persisted over 12 months
- All groups had persistently reduced QoL and low employment (0–50%); group 4 showed continuous survival decline
Methodological Strengths
- Prospective multicenter design across 21 ICUs
- Standardized functional, cognitive, psychiatric, and QoL assessments with 12-month follow-up
Limitations
- Observational design limits causal inference
- Generalizability may be limited to similar ICU settings and healthcare systems
Future Directions: Test phenotype-guided rehabilitation and mental health interventions, and integrate phenotype-based stratification into post-sepsis clinical trials.
3. Sepsis-Associated Acute Kidney Disease Incidence, Trajectory, and Outcomes.
Among 24,038 sepsis inpatients, 42.2% developed SA-AKI and 17.6% progressed to SA-AKD. Non-recovery SA-AKD phenotypes (relapse, persistent) had substantially higher 1-year risks of kidney replacement therapy and mortality versus recovery, delineating trajectories from AKI to CKD.
Impact: Defines actionable renal risk trajectories after sepsis, enabling post-discharge surveillance and nephrology referral strategies to prevent progression to CKD and dialysis.
Clinical Implications: Identify SA-AKD phenotypes before discharge and prioritize close renal follow-up for relapse/persistent groups with early nephrology co-management and kidney-protective strategies.
Key Findings
- Of 24,038 sepsis inpatients, 42.2% had SA-AKI; 17.6% progressed to SA-AKD
- SA-AKD subgroups: recovery (43.6%), relapse (8.3%), persistent (32.2%), unclassified (15.9%)
- Compared with recovery: 1-year mortality aHR 1.57 (relapse) and 1.36 (persistent); KRT initiation risk 3.27x (relapse) and 6.01x (persistent)
Methodological Strengths
- Large, longitudinal real-world cohort with standardized AKI/AKD definitions
- Multivariable Cox models to adjust for confounders and define risk trajectories
Limitations
- Retrospective single-center design with potential selection and information biases
- Kidney function follow-up not standardized across patients
Future Directions: Prospective validation of SA-AKD phenotypes, embed prediction tools in EHRs, and test targeted post-sepsis renal care pathways to reduce CKD progression.