Omega-3 fatty acids as host-directed immunomodulatory therapeutics in sepsis: real-world evidence supporting drug development potential for systemic inflammatory diseases.

Unadjusted ICU mortality was higher in the omega-3 FA group compared to controls.

• The unadjusted mortality rate was 32.7% in the omega-3 FA group and 24.6% in controls (p=0.032).
• Total sample included 633 patients: omega-3 FA group n=211, control n=422.
• Patients were admitted with sepsis to the ICU of Shenzhen People's Hospital between December 2016 and July 2019.
• Propensity score matching was applied at a 1:2 ratio between omega-3 FA-treated and control groups.

After multivariate adjustment, omega-3 FA supplementation demonstrated a significant independent protective effect on ICU mortality.

• Adjusted HR=0.60, 95% CI: 0.43-0.83, p=0.003.
• Covariates adjusted for included age, hemofiltration (HF) and norepinephrine (NE) requirements, CRP, lymphocyte count, SOFA score, and abdominal infection.
• Univariate analysis showed only a weak, non-significant protective effect (HR=0.74, 95% CI: 0.54-1.02, p=0.062).
• Both logistic regression and inverse probability of treatment weighting (IPTW) were performed to determine the independent effect.

Kaplan-Meier survival analysis confirmed improved survival in the omega-3 FA group.

• Kaplan-Meier analysis showed statistically significant improved survival in the omega-3 FA group (p=0.038).
• This finding was consistent with the adjusted multivariate analysis results.

Advanced age, elevated CRP, and higher norepinephrine dependence were identified as factors that negatively modulated omega-3 FA efficacy.

• These three factors were identified as negative modulators of omega-3 FA therapeutic efficacy in sepsis patients.
• Norepinephrine requirement, CRP, and lymphocyte count were among the covariates used in propensity score matching.
• These findings suggest that patient subgroups may respond differently to omega-3 FA supplementation.

The study design used propensity score matching to control for confounding between omega-3 FA-treated and control groups.

• PSM was applied at a 1:2 ratio between omega-3 FA-treated and control groups.
• Covariates used in matching included age, sex, diagnosis, norepinephrine requirement, hemofiltration, CRP, and lymphocyte count.
• The study was retrospective in design, conducted at a single center (Shenzhen People's Hospital).
• The study period spanned from December 2016 to July 2019.

The authors propose that omega-3 FAs have translational potential as adjunct host-directed therapeutics not only for sepsis but also for neglected tropical diseases.

• Sepsis and neglected tropical diseases share dysregulated inflammation and immune dysfunction mechanisms.
• The authors highlight omega-3 FAs' 'potent anti-inflammatory and immunomodulatory properties' as the basis for this translational potential.
• The findings are presented as supporting 'further drug development toward host-directed treatments for neglected tropical diseases.'