Lower Respiratory Tract Coinfection in the ICU: Prevalence and Clinical Significance of Coinfection Detected via Microbiological Analysis of Bronchoalveolar Lavage Fluid With a Comparison of Invasive Methodologies.

Pneumonia remains a significant cause of morbidity and mortality, with increasing interest in the detection and clinical significance of coinfection. Further investigation into the impact of bronchoalveolar lavage (BAL) sampling methodology and efficient clinical utilization of microbiological analyses is needed to guide the management of lower respiratory tract infection in the ICU. DESIGN: Retrospective observational study. SETTING: ICUs at a single center between August 1, 2012, and January 1, 2018. PATIENTS: Mechanically ventilated adult patients who underwent BAL testing during an ICU admission were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BAL methodology (bronchoscopic vs nonbronchoscopic), microbiological diagnostic testing, and clinical outcomes measures were obtained. Chi-square or Fisher exact tests assessed associations between categorical variables, whereas Kruskal-Wallis tests analyzed differences in distributions of measures. BAL samples from 803 patients met inclusion criteria. Coinfection was detected more frequently via bronchoscopic BAL compared with nonbronchoscopic BAL (26% vs 9%; p < 0.001). Viruses were detected more frequently in bronchoscopic (42% vs 13%; p < 0.001) and bacteria in nonbronchoscopic (42% vs 33%; p = 0.011) BALs. A positive correlation between mortality and the number of organisms isolated was identified, with 43%, 48%, and 58% 30-day mortality among those with 0, 1, and more than 2 organisms, respectively (p = 0.003). Viral organism detection was associated with increased 30-day mortality (56% vs 46%; p = 0.033). CONCLUSIONS: Even in the setting of standardized institutional techniques, retrospective evaluation of bronchoscopic and nonbronchoscopic BAL methodologies did not reveal similar microbiologic yield in critically ill patients, though bronchoscopic BAL overall yielded more organisms, and occurrence of multiple organisms in BAL was associated with worse outcome. Prospective data are needed for direct comparison of both methods to develop more standardized approaches for use in different patient groups.

Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity.

The aggregation of the amyloidogenic polypeptide IAPP (Islet Amyloid Polypeptide, amylin) is believed to play a direct role in the death of pancreatic ß-islet cells in type II diabetes. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the progression of this disease. Here, we investigate myricetin's potential as an inhibitor of IAPP aggregation. We show that myricetin prevented thioflavin T binding in a concentration dependent manner. Atomic force microscopy revealed that myricetin prevented fiber formation under rigorous conditions conducive to forming IAPP aggregates. Using an IAPP-EGFP (Enhanced Green Fluorescent Protein) protein construct, we find that high concentrations of myricetin slowed the in vivo aggregation of IAPP-EGFP. Myricetin was also found to rescue living mammalian cells from the toxic effects of IAPP. These results indicate that myricetin is a strong inhibitor of IAPP amyloid aggregation and a potential lead molecule for the development of an amyloid inhibiting therapeutic.