Early Physician Gestalt Versus Usual Screening Tools for the Prediction of Sepsis in Critically Ill Emergency Patients.

STUDY OBJECTIVE: Compare physician gestalt to existing screening tools for identifying sepsis in the initial minutes of presentation when time-sensitive treatments must be initiated. METHODS: This prospective observational study conducted with consecutive encounter sampling took place in the emergency department (ED) of an academic, urban, safety net hospital between September 2020 and May 2022. The study population included ED patients who were critically ill, excluding traumas, transfers, and self-evident diagnoses. Emergency physician gestalt was measured using a visual analog scale (VAS) from 0 to 100 at 15 and 60 minutes after patient arrival. The primary outcome was an explicit sepsis hospital discharge diagnosis. Clinical data were recorded for up to 3 hours to compare Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA), Modified Early Warning Score (MEWS), and a logistic regression machine learning model using Least Absolute Shrinkage and Selection Operator (LASSO) for variable selection. The screening tools were compared using receiver operating characteristic analysis and area under the curve calculation (AUC). RESULTS: A total of 2,484 patient-physician encounters involving 59 attending physicians were analyzed. Two hundred seventy-five patients (11%) received an explicit sepsis discharge diagnosis. When limited to available data at 15 minutes, initial VAS (AUC 0.90; 95% confidence interval [CI] 0.88, 0.92) outperformed all tools including LASSO (0.84; 95% CI 0.82 to 0.87), qSOFA (0.67; 95% CI 0.64 to 0.71), SIRS (0.67; 95% 0.64 to 0.70), SOFA (0.67; 95% CI 0.63 to 0.70), and MEWS (0.66; 95% CI 0.64 to 0.69). Expanding to data available at 60 minutes did not meaningfully change results. CONCLUSION: Among adults presenting to an ED with an undifferentiated critical illness, physician gestalt in the first 15 minutes of the encounter outperformed other screening methods in identifying sepsis.

Choline Supplementation Partially Restores Dendrite Structural Complexity in Developing Iron-Deficient Mouse Hippocampal Neurons.

BACKGROUND: Fetal-neonatal iron deficiency causes learning/memory deficits that persist after iron repletion. Simplified hippocampal neuron dendrite structure is a key mechanism underlying these long-term impairments. Early life choline supplementation, with postnatal iron repletion, improves learning/memory performance in formerly iron-deficient (ID) rats. OBJECTIVES: To understand how choline improves iron deficiency-induced hippocampal dysfunction, we hypothesized that direct choline supplementation of ID hippocampal neurons may restore cellular energy production and dendrite structure. METHODS: Embryonic mouse hippocampal neuron cultures were made ID with 9 µM deferoxamine beginning at 3 d in vitro (DIV). At 11 DIV, iron repletion (i.e., deferoxamine removal) was performed on a subset of ID cultures. These neuron cultures and iron-sufficient (IS) control cultures were treated with 30 µM choline (or vehicle) between 11 and 18 DIV. At 18 DIV, the independent and combined effects of iron and choline treatments (2-factor ANOVA) on neuronal dendrite numbers, lengths, and overall complexity and mitochondrial respiration and glycolysis were analyzed. RESULTS: Choline treatment of ID neurons (ID + Cho) significantly increased overall dendrite complexity (150, 160, 180, and 210 µm from the soma) compared with untreated ID neurons to a level of complexity that was no longer significantly different from IS neurons. The average and total length of primary dendrites in ID + Cho neurons were significantly increased by ∼15% compared with ID neurons, indicating choline stimulation of dendrite growth. Measures of mitochondrial respiration, glycolysis, and ATP production rates were not significantly altered in ID + Cho neurons compared with ID neurons, remaining significantly reduced compared with IS neurons. Iron repletion significantly improved mitochondrial respiration, ATP production rates, overall dendrite complexity (100-180 µm from the soma), and dendrite and branch lengths compared with untreated ID neurons. CONCLUSIONS: Because choline partially restores dendrite structure in ID neurons without iron repletion, it may have therapeutic potential when iron treatment is not possible or advisable. Choline's mechanism in ID neurons requires further investigation.