Daily Sepsis Research Analysis

IMPORTANCE: Sepsis remains a leading cause of death in infectious cases. The heterogeneity of immune responses is a major challenge in the management and prognostication of patients with sepsis. Identifying distinct immune response subphenotypes using parsimonious classifiers may improve outcome prediction, particularly in resource-limited settings. OBJECTIVES: This study aimed to evaluate whether classification of the immune response can serve as a predictor of mortality. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted in the emergency department, inpatient wards, and ICU of a tertiary hospital. Adult patients diagnosed with sepsis within the previous 24 hours were included. Exclusion criteria were history of RBC transfusion, major thalassemia, decompensated cirrhosis, hematologic malignancy, or use of immunosuppressive or chronic corticosteroid therapy. Demographic, clinical, and laboratory data-including serum ferritin and monocyte human leukocyte antigen-DR/Human Leukocyte Antigen-DR) (mHLA-DR) levels-were collected. MAIN OUTCOMES AND MEASURES: Subjects were classified into the following immune subphenotypes: macrophage activation-like syndrome (MALS) (if ferritin > 4420 ng/mL), immunoparalysis (if mHLA-DR < 10,000 receptors/cell and ferritin ≤ 4420 ng/mL), and unclassified (if they did not meet the criteria for either MALS or immunoparalysis). The primary outcome was in-hospital mortality. RESULTS: Of the 200 subjects recruited, 54 (27%) were classified into the MALS group, 19 (9.5%) into the immunoparalysis group, and the remainder into the unclassified group. The in-hospital mortality rates for the MALS, immune paralysis, and unclassified groups were 83.3%, 68.4%, and 51.1%, respectively. The proportional hazards assumption was met between the MALS and unclassified groups (crude hazard ratio [HR] 2.3; 95% CI, 1.56-3.35) but not between the immunoparalysis and unclassified groups (crude HR 1.4; 95% CI, 0.76-2.50). After adjusting for confounding variables, MALS's adjusted HR was 1.7 (95% CI, 1.13-2.49; p = 0.01). CONCLUSIONS AND RELEVANCE: The MALS subphenotype is an independent predictor of in-hospital mortality in sepsis.

INTRODUCTION: Sepsis remains a leading cause of mortality, with mortality from septic shock exceeding 40%. Standardized resuscitation (30 mL/kg) may cause adverse outcomes, including fluid overload or prolonged hypotension, emphasizing the need for individualized strategies. Sepsis-induced shock arises from varying degrees of vasodilation and hypovolemia, yet patients often present with similar clinical signs in the emergency department (ED). Photoplethysmography (PPG), a non-invasive technique reflecting peripheral perfusion, may help identify patients with a predominant vasodilatory profile who could benefit from early vasopressor therapy. METHODS: This post hoc analysis used data from the Acutelines biobank at the University Medical Centre Groningen. Adults admitted for non-trauma specialties with suspected infection and hemodynamic instability (MAP < 70 mmHg, SBP < 90 mmHg, shock index > 0.9, or lactate > 4.0 mmol/L) were included. PPG data were pre-processed and features extracted. Principal component analysis (PCA) and K-means clustering enabled dimensionality reduction and hemodynamic profiling. Logistic regression assessed the discriminative performance of PPG-based models for vasopressor therapy initiation within 24 h. RESULTS: Among 325 patients, 16.3% received vasopressors. PCA identified three principal components explaining 80.3% of variance: PC1 (arterial compliance), PC2 (cardiac output and systemic vascular resistance), and PC3 (peripheral vasomotor tone). The PPG-based model showed moderate discriminative power (AUROC: 0.75), improving when combined with MAP and lactate (AUROC: 0.83). CONCLUSION: PPG enables identification of patients likely to benefit from vasopressor therapy during the first 20 min after ED arrival. By providing additional insight into peripheral perfusion, this proof-of-principle study supports further exploration of PPG as a clinical support tool for personalized hemodynamic resuscitation in sepsis. EDITORIAL COMMENT: This secondary analysis demonstrates early peripheral circulatory patterns in sepsis using photoplethysmography at the start of resuscitation. Distinct PPG-derived profiles were associated with vasopressor initiation within 24 h, supporting PPG as a tool for personalized resuscitation.

OBJECTIVES BACKGROUND: Monocyte anisocytosis (monocyte distribution width [MDW]) has been previously validated to predict sepsis and outcome in patients presenting in the emergency department and mixed-population ICUs. Determining sepsis in a critically ill surgical/trauma population is often difficult due to concomitant inflammation and stress. We examined whether MDW could identify sepsis among patients admitted to a surgical/trauma ICU and predict clinical outcome. DESIGN: Secondary analysis of three prospective observational clinical studies. SETTING: Single institution ICU. PATIENTS/SUBJECTS: Two hundred thirty-eight participants were included in this study: 107 patients who were admitted to the ICU and adjudicated to have sepsis, 80 patients who were considered critically ill nonseptic (CINS), and 51 healthy control participants. INTERVENTIONS: MDW was measured among hospitalized patients admitted to the ICU with the diagnosis of sepsis or CINS patients at risk of developing sepsis. Blood samples were collected at admission and at intervals during ICU admission. MEASUREMENTS AND MAIN RESULTS: MDW significantly differed between septic and CINS patients on ICU admission (26.4, interquartile range [IQR, 23.5-30.8] vs. 20.1 [IQR, 17.9-21.9]; p < 0.001) and could discriminate with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.79-0.91; p < 0.001). An MDW of greater than 22.0 at admission to the ICU could identify sepsis with a 78% specificity and a 90% sensitivity but could not discriminate in-hospital, 30-day, or 90-day mortality. LIMITATIONS: Small sample size from a single institution. Our analysis did not include other relevant biomarkers such as procalcitonin, C-reactive protein, and interleukin-6. In the imputation of missing values, linear mixed-effect models were used, risking model misspecification and the violation of the missing-at-random assumption. CONCLUSIONS: Among surgical/trauma ICU patients, MDW can discriminate between sepsis and nonseptic inflammation, but it is a weak predictor of mortality.