Development of a point-of-care inflammatory biomarkers panel in sepsis management

Thesis Abstract

In the management of sepsis, rapid, accurate assessment of inflammatory status is critical for timely therapeutic decisions and improved patient outcomes, yet current workflows rely on single biomarkers that inadequately capture the dynamic host response and are hindered by limited availability in resource-constrained settings. This study aims to design, implement, and evaluate a point-of-care (POC) inflammatory biomarkers panel that integrates multiplexed assays for early detection, risk stratification, and treatment guidance in adult sepsis patients. Specific objectives are (i) to identify a multi-biomarker panel comprising validated inflammatory and innate immune markers (including IL-6, TNF-?, CRP, PCT, IL-10, HMGB1, and neutrophil CD64) that optimizes diagnostic accuracy and prognostic value; (ii) to develop a POC device-based workflow enabling rapid sample-to-result turnaround within 60 minutes for emergency department and intensive care unit settings; (iii) to evaluate analytical performance (sensitivity, specificity, linearity, precision) and clinical performance (predictive value for organ dysfunction, septic shock progression, and 28-day mortality) in a prospective, multicenter cohort; and (iv) to assess clinician usability, decision-making impact, and health-economic implications. The study adopts a pragmatic, mixed-methods design underpinned by the diffusion of innovations theory and the construct of actionable biomarker panels in clinical decision support. A prospective observational cohort of 520 adult sepsis patients will be recruited across three tertiary hospitals. At enrollment, venous blood samples will be collected for simultaneous measurement of the biomarker panel using a lab-developed multiplex immunoassay integrated into a microfluidic POC platform (lateral-flow + microarray readout) and standard laboratory assays as reference. Data will include demographic and clinical variables, Sequential Organ Failure Assessment (SOFA) scores, vascular and hemodynamic parameters, microbiology results, and 28-day outcomes. The analytical performance of the POC panel will be assessed using Bland-Altman analysis, Passing-Bablok regression, and receiver operating characteristic (ROC) curve analysis to determine optimal thresholds for diagnosis, risk stratification, and prognosis. Multivariate logistic regression and time-to-event (Cox proportional hazards) models will evaluate the incremental value of the biomarker panel over conventional scoring systems. Subgroup analyses will explore performance across age strata, comorbidity burden, source of infection, and pathogen type. Health economic evaluation will compare cost per correctly identified high-risk patient and cost per quality-adjusted life year (QALY) gained, informed by decision-analytic modeling. Qualitative data from semi-structured interviews with clinicians will be analyzed using thematic analysis to assess usability, perceived impact on clinical workflow, and barriers to adoption. Expected findings include that the multi-marker POC panel demonstrates superior diagnostic accuracy (AUC ? 0.90 for bacteremia differentiation) and improved prognostic discrimination (substantial incremental gain in SOFA-associated mortality risk prediction) relative to single biomarkers and standard-of-care tests, with rapid assay turnaround (<60 minutes) enabling earlier initiation of targeted therapies. The study anticipates favorable clinician acceptance and a positive impact on decision-making efficiency, balanced by considerations of cost and integration challenges into existing electronic medical record systems. The contribution to knowledge lies in validating a clinically actionable, scalable POC biomarker panel that captures the dynamic inflammatory milieu of sepsis, bridging biomarker science with bedside decision support, and providing evidence on implementation, economic viability, and patient outcomes in diverse hospital settings. The conclusions will discuss the panel’s potential to standardize early sepsis management, reduce unnecessary antibiotic exposure, and inform personalized treatment pathways, with recommendations for broader multicenter validation, harmonization of assay platforms, and integration into national sepsis guidelines to optimize patient care and health-system performance.