Metabolic Heterogeneity in Human Lung Tumors.

Non-small cell lung cancer (NSCLC) is heterogeneous in the genetic and environmental parameters that influence cell metabolism in culture. Here, we assessed the impact of these factors on human NSCLC metabolism in vivo using intraoperative (13)C-glucose infusions in nine NSCLC patients to compare metabolism between tumors and benign lung. While enhanced glycolysis and glucose oxidation were common among these tumors, we observed evidence for oxidation of multiple nutrients in each of them, including lactate as a potential carbon source. Moreover, metabolically heterogeneous regions were identified within and between tumors, and surprisingly, our data suggested potential contributions of non-glucose nutrients in well-perfused tumor areas. Our findings not only demonstrate the heterogeneity in tumor metabolism in vivo but also highlight the strong influence of the microenvironment on this feature.

Probable Encephalopathy and Spasticity in a Multiple Sclerosis Patient Following Carbapenem Administration: A Case Report and Brief Literature Review.

Purpose: The purpose of this case report is to describe spasticity and encephalopathy that developed in a multiple sclerosis patient following carbapenem administration. Summary: A 55-year-old female with multiple sclerosis developed spasticity and encephalopathy within 24 hours of meropenem and ertapenem administration. This was the second time that she had developed encephalopathy following carbapenem administration. The patient gradually recovered over four days following discontinuation of carbapenem therapy. Conclusion: Carbapenem neurotoxicity, a well-documented adverse effect, has been linked to several risk factors, including central nervous system lesions. Despite this, there is little evidence describing the risk of neurotoxicity in patients with multiple sclerosis. It is important to understand the potential adverse effects of carbapenems in specific patient populations to help guide appropriate treatment of infections.

Bronchoalveolar Lavage Gram Stains for Early Bacterial Identification in Pneumonia: Should They Stay or Should They Go?

OBJECTIVES: The primary endpoint was to determine the sensitivity and specificity of the bronchoalveolar lavage Gram stain in predicting culture results. Secondary endpoints included determining the proportion of Gram stains from bronchoalveolar lavages that accurately identify culture isolates and the duration of antibiotic treatment before bronchoalveolar lavage collection. DESIGN: Retrospective, observational study. SETTING: Four ICUs at a single academic medical center. SUBJECTS: Patients at least 18 years old admitted to an ICU with a diagnosis of pneumonia, collection of a bronchoalveolar lavage sample, and receipt of antibiotics. MEASUREMENTS AND MAIN RESULTS: Two-hundred five isolates were included. Gram stains for Gram-positive and Gram-negative isolates showed high specificity, 97.3% and 100%, respectively, but lower sensitivity at 61.9% and 54.2%, respectively. The positive predictive value and negative predictive value were 77.2% and 95.7% for Gram-positive isolates and 100% and 84.4% for Gram-negative isolates, respectively. Gram stains correctly identified isolates on the bronchoalveolar lavage culture in 61.9% of Gram-positive organisms and in 54.2% of Gram-negative organisms. CONCLUSIONS: Gram stains accurately identified causative organisms in a limited number of patients making the utility of the Gram stain an uncertain modality for predicting causative respiratory pathogens from bronchoalveolar lavage samples.

The gut commensal Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape.

The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) causes severe diarrhea, but the influence of the gut microbiota on EHEC infection is largely unknown. A predominant member of the microbiota, Bacteroides thetaiotaomicron (Bt), is resident at EHEC attachment sites. We show that Bt enhances EHEC virulence gene expression through the transcription factor Cra, which is functionally sensitive to sugar concentrations. This enhanced virulence accompanies increased formation of attaching and effacing (AE) lesions requisite for EHEC colonization. Infection with Citrobacter rodentium, a natural mouse pathogen homologous to EHEC, in Bt-reconstituted mice results in increased gut permeability along with exacerbated host pathology and mortality compared to mice deplete of microflora. Bt modifies the metabolite environment at infection sites, increasing metabolites involved in gluconeogenesis, with stark increases in succinate, which can be sensed by Cra. Our findings suggest that microbiota composition affects disease outcome and may explain links between microbiota composition and disease susceptibility.