Evaluating Yield of 19 Versus 21 G EBUS-TBNA Needles: A Prospective Study.

BACKGROUND: Controversy remains regarding the effect of needle size on the diagnostic yield of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration. We conducted a prospective study comparing the diagnostic yield of 19 and 21 G EBUS needles and hypothesized that the 19 G have a greater EBUS-guided transbronchial needle aspiration diagnostic yield as compared with the 21 G needle. METHODS: A total of 60 patients undergoing EBUS-guided transbronchial needle aspiration were enrolled with informed consent. Both 19 and 21 G needles were used at each lymph node station in alternating fashion, we randomized which needle, to begin with. Two rapid on-site cytology evaluation stations were present and assigned to one of the 2 needles. They reported sample adequacy and prepared a separate cell block per lymph node sampled for their assigned needle. RESULTS: A total of 141 lymph nodes were analyzed. Diagnosis included 69 benign lymph nodes, 47 malignant lymph nodes, 22 noncaseating granulomas, and 3 infected lymph nodes. Five hundred seventy-three passes (average: 4.1 passes/lymph node) were done with 19 G and 581 passes with 21 G needles (average: 4.1 passes/lymph node). Diagnostic yield was similar between 19 and 21 G needles overall (89.4% vs. 88.7%, P=0.71). The 19 G needles showed higher smear cellularity (32.6% vs. 13.0%, P=0.05), and rapid on-site cytology evaluation adequacy (84.8% vs. 63.0%, P=0.004) in lymph nodes with cancer diagnosis. In 7 of the 141 lymph nodes, samples from only one of the needles provided the final diagnosis. CONCLUSION: There is no difference in the overall diagnostic yield between 19 and 21 G needles. Further studies are needed to confirm the trend of the superiority of 19 G in cancerous lymph nodes.

Interactions between the gut microbiome and host gene regulation in cystic fibrosis.

BACKGROUND: Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in the CFTR gene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions. Advancements in medical care have led to markedly increased longevity of patients with cystic fibrosis, but new complications have emerged, such as early onset of colorectal cancer. Although the pathogenesis of colorectal cancer in cystic fibrosis remains unclear, altered host-microbe interactions might play a critical role. To investigate this, we characterized changes in the microbiome and host gene expression in the colonic mucosa of cystic fibrosis patients relative to healthy controls, and identified host gene-microbiome interactions in the colon of cystic fibrosis patients. METHODS: We performed RNA-seq on colonic mucosa samples from cystic fibrosis patients and healthy controls to determine differentially expressed host genes. We also performed 16S rRNA sequencing to characterize the colonic mucosal microbiome and identify gut microbes that are differentially abundant between patients and healthy controls. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression. RESULTS: We find that 1543 genes, including CFTR, show differential expression in the colon of cystic fibrosis patients compared to healthy controls. These genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of colorectal cancer, tumor suppression, p53, and mTOR signaling pathways. In addition, patients with cystic fibrosis show decreased gut microbial diversity, decreased abundance of butyrate producing bacteria, such as Ruminococcaceae and Butyricimonas, and increased abundance of other taxa, such as Actinobacteria and Clostridium. An integrative analysis identified colorectal cancer-related genes, including LCN2 and DUOX2, for which gene expression is correlated with the abundance of colorectal cancer-associated bacteria, such as Ruminococcaceae and Veillonella. CONCLUSIONS: In addition to characterizing host gene expression and mucosal microbiome in cystic fibrosis patients, our study explored the potential role of host-microbe interactions in the etiology of colorectal cancer in cystic fibrosis. Our results provide biomarkers that may potentially serve as targets for stratifying risk of colorectal cancer in patients with cystic fibrosis.

Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.

Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these changes can be used to understand microbe-host interactions with potential functional biological relevance. Here, we characterized the association between CRC microbial communities and tumor mutations using microbiome profiling and whole-exome sequencing in 44 pairs of tumors and matched normal tissues. We found statistically significant associations between loss-of-function mutations in tumor genes and shifts in the abundances of specific sets of bacterial taxa, suggestive of potential functional interaction. This correlation allows us to statistically predict interactions between loss-of-function tumor mutations in cancer-related genes and pathways, including MAPK and Wnt signaling, solely based on the composition of the microbiome. In conclusion, our study shows that CRC microbiomes are correlated with tumor mutational profiles, pointing towards possible mechanisms of molecular interaction.

Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease.

Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung.

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis.

BACKGROUND: Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance. METHODS: We analyzed prospectively collected results of colonoscopies initiated at age 40years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30-39years performed during the same time period at the Center. RESULTS: The incidence of polyp detection increased markedly after age 40 in CF patients. Greater than 50% were found to have adenomatous polyps; approximately 25% had advanced adenomas as defined by size and/or histopathology; 3% were found to have colon cancer. Multivariate analysis demonstrated specific risk factors for adenoma formation and progression. CONCLUSIONS: Early screening and more frequent surveillance should be considered in patients with CF due to early incidence and progression of adenomas in this patient population.

The association of serum bilirubin levels on the outcomes of severe sepsis.

PURPOSE: Admission serum bilirubin levels have been incorporated into severity of illness scoring systems in critical illness as a marker of liver dysfunction. The purpose of our study is to determine the independent association of serum bilirubin with mortality in severe sepsis and septic shock. METHODS: We conducted a retrospective study of adult patients admitted with severe sepsis and septic shock. We excluded patients with a prior history of liver disease. We identified the highest serum bilirubin within 72 hours of admission and stratified bilirubin levels into ≤1 mg/dL (normal), 1.1 to 2 mg/dL (abnormal up to 2 mg/dL), and >2 mg/dL. We sought to determine the independent association of hyperbilirubinemia with mortality and length of intensive care unit stay in persons with severe sepsis and septic shock. RESULTS: A total of 251 patients met criteria for severe sepsis. In all, 200 patients had a bilirubin of <1 mg/dL, and 51 had a bilirubin of >1 mg/dL. Of these 51, 12 had a bilirubin >2 mg/dL. Mortality was 12%, 24%, and 42% in persons with a bilirubin ≤1, 1.1 to 2, and >2 mg/dL, respectively. Compared to those with a bilirubin ≤ 1 mg/dL, adjusted odds of mortality in patients were 3.85 (95% confidence interval [CI] 1.21-12.2) and 9.85 (95% CI 1.92-50.5) times higher in persons with bilirubin levels between 1.1 and 2 and >2 mg/dL, respectively. CONCLUSION: After multivariable adjustment for potential confounding factors, elevated serum bilirubin levels within 72 hours of admission are associated with an increased risk of mortality in patients with severe sepsis and septic shock. Prospective studies are warranted to further validate our findings.