Laura Ruano

BACKGROUND: Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome. METHODS: This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f T>MIC) and 100% (100% f T>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome. RESULTS: We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T>MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% f T>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status. CONCLUSIONS: Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.

OBJECTIVE: To examine whether patients with acute hypoxemia and bilateral opacities treated with high-flow nasal cannula and acute respiratory distress syndrome patients who were directly mechanically ventilated are similar in terms of lung epithelial, endothelial, and inflammatory biomarkers. DESIGN: Prospective, multicenter study. SETTING: ICUs at three university tertiary hospitals. PATIENTS: Intubated and nonintubated patients admitted to the ICU with acute hypoxemia (PaO2/FIO2 ≤ 300) and bilateral opacities. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Either high-flow nasal cannula or mechanical ventilation was initiated, at the discretion of the attending physician. We measured plasma biomarkers of lung epithelial injury (receptor for advanced glycation end products and surfactant protein D) and endothelial injury (angiopoietin-2) and inflammation (interleukin-6, interleukin-8, and interleukin-33 and soluble suppression of tumorigenicity-2) within 24 hours of acute respiratory distress syndrome onset. Propensity score matching was performed using six different variables (Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, PaO2/FIO2, origin of acute respiratory distress syndrome, steroids, renal failure and need for vasopressors). Nonhypoxemic mechanically ventilated critically ill patients and healthy volunteers served as controls. Of the 170 patients enrolled, 127 (74.7%) were intubated and 43 (25.3%) were treated with high-flow nasal cannula at acute respiratory distress syndrome onset. After propensity score matching (39 high-flow nasal cannula patients vs 39 mechanical ventilation patients), no significant differences were observed in receptor for advanced glycation end products, surfactant protein D, angiopoietin-2, interleukin-6, interleukin-8, interleukin-33, and soluble suppression of tumorigenicity-2 between matched patients who were treated with high-flow nasal cannula and those who were intubated at acute respiratory distress syndrome onset. After matching, no differences in mortality or length of stay were observed. All biomarkers (with the exception of interleukin-33) were higher in both groups of matched acute respiratory distress syndrome patients than in both control groups. CONCLUSIONS: Acute hypoxemic patients with bilateral infiltrates treated with high-flow nasal cannula presented a similar pattern of biomarkers of inflammation and injury to acute respiratory distress syndrome patients undergoing direct mechanical ventilation. The results suggest that these high-flow nasal cannula patients should be considered as acute respiratory distress syndrome patients.

BACKGROUND: Asbestos body (AB) counting by a single observer is the most commonly used objective technique to demonstrate asbestos deposition in the lung. In this study, the accuracy and reliability of this procedure is analyzed by evaluating the degree of agreement between two experienced readers. METHODS: Lung tissue specimens from 66 individuals, most of whom had not been exposed to asbestos, were studied: 35 were obtained in postmortem studies (upper, middle, and lower lung) and 31 were from patients who underwent surgery for lung cancer. Overall, 167 samples were analyzed. Lung tissue sections weighing 0.5 g were obtained prospectively and processed, and the inorganic residue was analyzed by light microscopy at 400× magnification by two experienced readers. Results were expressed as AB/g of dry lung tissue. Interobserver variability was analyzed using the Spearman correlation coefficient and agreement was evaluated by the Bland-Altman method and the kappa index. RESULTS: The interobserver correlation was 0.8975: 0.8029 for autopsy samples and 0.9592 for biopsy samples. Bland-Altman plots showed that most values were grouped around the 95% limits of agreement. The kappa index was 0.87 for all samples, and 0.79, 0.65, and 0.54 for upper, middle, and lower lung specimens, respectively. CONCLUSIONS: Asbestos body counting by a single reader is a reliable method, especially at low concentrations of asbestos bodies in lung tissue. Double reading may be indicated in borderline cases with asbestos body levels close to levels of 1 000 AB/g.