B-147 Biomarker NMI: early Warning, Differential Diagnosis, and Treatment Monitoring in Sepsis

Abstract

Sepsis remains a life-threatening condition with no definitive gold standard for diagnosis, leading to reliance on nonspecific clinical criteria and traditional markers. Clinicians face three major challenges: (1) difficulty in early warning and detection, (2) rapid identification of the infection source, and (3) monitoring whether antibiotic treatment is appropriate and targeted. These gaps contribute to delayed intervention, overuse/misuse of antibiotics, and poor outcomes. This study evaluates N-Myc and STAT interactor (NMI), a novel serum protein biomarker reflecting the host immune response, for its potential to address these challenges, particularly early warning, definite diagnosis, and treatment monitoring, while offering superior performance over conventional inflammatory markers. A combined retrospective (n=984 total: 242 sepsis patients, 351 non-sepsis disease controls, 391 healthy control) and prospective (n=1219 total: 202 sepsis patients, 158 non-sepsis infection controls, 471 non-infectious shock/organ dysfunction cases, 388 healthy controls) multicenter observational study were conducted. Serum NMI levels were measured using a Rapid chemiluminescent immunoassay. Diagnostic performance was assessed by ROC analysis (AUC, sensitivity/specificity) versus procalcitonin (PCT), C-reactive protein (CRP) and Interleukin-6 (IL-6). Prognostic value was evaluated via 28-day mortality using Kaplan–Meier survival analysis and log-rank test. In the retrospective cohort, serum NMI levels were significantly elevated in sepsis patients compared to both non-septic controls and healthy individuals (both p<0.001), and achieved an AUC of 0.85 (95%CI:0.82-0.89) for distinguishing sepsis from non-sepsis. In the prospective cohort, NMI demonstrated superior diagnostic accuracy for sepsis (AUC=0.88, 95%CI: 0.85 - 0.91), outperforming PCT, CRP, and IL-6. At the optimal Youden index, NMI showed high specificity in distinguishing septic shock from non-infectious shock (AUC=0.89, specificity =100%) and infectious from non-infectious organ dysfunction (e.g., AUC=0.93, specificity =100% for trauma-induced; AUC=0.90, specificity=94% for pancreatitis-induced). In addition, a small patient-number cohort showed that NMI level enabled early warning by detecting elevations prior to clinical deterioration, and Longitudinal monitoring showed NMI kinetics correlating with appropriate antibiotic response (rapid decline in responders vs. persistent elevation in non-responders), addressing treatment appropriateness. Furthermore, Lower baseline/early NMI levels were strongly associated with reduced 28-day mortality (p<0.01). NMI emerges as a highly accurate, specific novel serum biomarker that effectively tackles key sepsis challenges: enabling early warning, supporting definite diagnosis via host immune response reflection, and facilitating monitoring of targeted antibiotic therapy. NMI offers substantial added value for timely intervention and personalized management. These findings position NMI-based IVD technology as a promising, transformative tool to enhance sepsis early intervention, optimize antibiotic stewardship, and advance clinical practice.