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BACKGROUND: The impact of inhalation injury on risk of nosocomial pneumonia (NP), an important complication in patients with burns, is not well established. RESEARCH QUESTION: Is more severe inhalation injury associated with increased risk of NP? STUDY DESIGN AND METHODS: We performed a retrospective cohort study of patients with suspected inhalation injury admitted to a regional burn center from 2011 to 2022 who underwent diagnostic bronchoscopy within 48 h of admission. We estimated the association of high-grade inhalation injury (Abbreviated Injury Scale score 3 and 4) vs low-grade inhalation injury (Abbreviated Injury Scale score 1 and 2) with NP adjusted for age, burn size, and comorbid obstructive lung disease. Death and hospital discharge were considered competing risks. RESULTS: Of the 245 patients analyzed, 51 (21%) had high-grade injury, 180 (73%) had low-grade injury, and 14 (6%) had no inhalation injury. Among the 236 patients hospitalized for ≥ 48 h, NP occurred in 24 of 50 patients (48%) in the high-grade group, 54 of 172 patients (31%) in the low-grade group, and two of 14 patients (14%) in the no inhalation injury group. High-grade (vs low-grade) inhalation injury was associated with higher hazard of NP in both the proportional cause-specific hazard model (cause-specific hazard ratio, 2.04; 95% CI, 1.26-3.30; P = .004) and Fine-Gray subdistribution hazard model (subdistribution hazard ratio for NP, 2.24; 95% CI, 1.38-3.64; P = .001). INTERPRETATION: Among patients with inhalation injury, more severe injury was associated with higher hazard of NP in competing risk analysis. Additional research is needed to investigate mechanisms that may explain the relationship between inhalation injury and NP and to identify more effective risk reduction strategies.
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Purpose: Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial. Methods: We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction. Results: Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen's Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) (p-value-for-interaction = 0.03). Conclusion: Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.