Intraoperative fluorescence imaging with indocyanine green in hepatic resection for malignancy: a systematic review and meta-analysis of diagnostic test accuracy studies.

BACKGROUND: Fluorescence imaging during hepatic resection has the potential to identify additional malignant tumors, increasing the chance for complete tumor resection. Indocyanine green (ICG) is an FDA approved, fluorescent dye used in a variety of surgical procedures. The objective of this study was to define the sensitivity of intraoperative ICG fluorescent imaging in the detection of hepatic malignancy in adult patients during hepatic resection, which was accomplished by performing a systematic review and meta-analysis. METHODS: The databases Medline, EMBASE, Scopus and Web of Science were assessed in September 2018. Article inclusion criteria was (1) Liver resection for malignancy (2) ICG injected pre or intraoperatively (3) Use of infrared electronic endoscopy or near-infrared fluorescence imaging intraoperatively (4) Patient age ≥ 18 years (5) N > 5 patients (6) Human and English studies only. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines were used for quality assessment. Data synthesis was completed using Meta-Disc and MedCalc software. A DerSimonian-Laird random effects model was used for the meta-analysis. RESULTS: 21 studies and 841 patients were included in our systematic review. Seven studies and 319 patients were included in the meta-analysis. The pooled sensitivity of intraoperative ICG fluorescence was 0.75 (0.71-0.79). Sensitivity for superficial tumors ranged from 0.96 to 1.00. Heterogeneity (I2) was calculated at 65.1%. ICG-related fluorescence imaging detected new malignant tumors not detected by conventional means in 42 of 362 patients across 13 studies. CONCLUSION: The sensitivity of intraoperative ICG-related imaging for superficial tumors is high; however, overall sensitivity is low, at 0.75, suggesting that it would have to be used in combination with current identification methods such as intraoperative ultrasound. Our study also found that intraoperative ICG fluorescence imaging was able to detect additional malignant hepatic tumors in 11.6% of patients.

The effects of inhaled aztreonam on the cystic fibrosis lung microbiome.

BACKGROUND: Aztreonam lysine for inhalation (AZLI) is an inhaled antibiotic used to treat chronic Pseudomonas aeruginosa infection in CF. AZLI improves lung function and quality of life, and reduces exacerbations-improvements attributed to its antipseudomonal activity. Given the extremely high aztreonam concentrations achieved in the lower airways by nebulization, we speculate this may extend its spectrum of activity to other organisms. As such, we sought to determine if AZLI affects the CF lung microbiome and whether community constituents can be used to predict treatment responsiveness. METHODS: Patients were included if they had chronic P. aeruginosa infection and repeated sputum samples collected before and after AZLI. Sputum DNA was extracted, and the V3-hypervariable region of the 16S ribosomal RNA (rRNA) gene amplified and sequenced. RESULTS: Twenty-four patients naïve to AZLI contributed 162 samples. The cohort had a median age of 37.1 years, and a  median FEV1 of 44% predicted. Fourteen patients were a priori defined as responders for achieving ≥3% FEV1 improvement following initiation. No significant changes in alpha diversity were noted following AZLI. Furthermore, beta diversity demonstrated clustering with respect to patients, but had no association with AZLI use. However, we did observe a decline in the relative abundance of several individual operational taxonomic units (OTUs) following AZLI initiation suggesting that specific sub-populations of organisms may be impacted. Patients with higher abundance of Staphylococcus and anaerobic organisms including Prevotella and Fusobacterium were less likely to respond to therapy. CONCLUSIONS: Results from our study suggest potential alternate/additional mechanisms by which AZLI functions. Moreover, our study suggests that the CF microbiota may be used as a biomarker to predict patient responsiveness to therapy suggesting the microbiome may be harnessed for the personalization of therapies.

The Evolving Cystic Fibrosis Microbiome: A Comparative Cohort Study Spanning 16 Years.

RATIONALE: The cystic fibrosis (CF) airways are infected with a diverse polymicrobial community. OBJECTIVES: Understanding how changes in the CF microbiome have occurred over time, similar to the observed changes in the prevalence of cultured pathogens, is key in understanding the microbiome's role in disease. METHODS: Drawing from a prospectively collected and maintained sputum biobank, we identified 45 patients with sputum samples collected between the ages of 18 and 21 years in three successive cohorts of adults transitioning to our CF clinic: A (1997-2000), B (2004-2007), and C (2010-2013). Patient demographics, clinical status, and medications were collected from detailed chart review. Microbial communities were assessed by Ilumina MiSeq sequencing of the variable 3 (V3) region of the 16S rDNA. RESULTS: The three cohorts were similar with respect to baseline demographics. There was a trend toward improved health and use of disease-modifying therapies in each successive cohort. Shannon diversity increased in the most recent cohort, suggesting an increase in the diversity of organisms between cohorts. Furthermore, the proportion of samples with Pseudomonas-dominated communities decreased over time, whereas Streptococcus increased. Although ß-diversity was associated with transition cohort, the greatest predictor of diversity remained lung function. Furthermore, core microbiome constituents were preserved across cohorts. CONCLUSIONS: Modest changes in the composition and structure of the microbiome of three successive cohorts of young adults with CF were observed, occurring in parallel with successive improvements in clinical status. Importantly, however, the core microbiome constituents were preserved across cohorts.

Effect of freezing sputum on Pseudomonas aeruginosa population heterogeneity.

Pseudomonas aeruginosa develops profound population heterogeneity in CF airways. How changes in these populations relate to clinical status is unknown. In order to facilitate this understanding, frequent sampling of this community is required. To determine if the collection and storage of sputum at home may pose a viable option, we collected sputum from ten patients. Sputum samples were partitioned in two, with half immediately processed on MacConkey agar and half assessed after freezing for one week in a home-freezer. From each sample, 88 isolates were assessed for antibiotic susceptibility and virulence factor production. Freezing resulted in a 103CFU/ml drop in P. aeruginosa. However, across 1760 isolates, no consistent difference in either antibiotic susceptibility nor virulence factors was observed suggesting freezing induced indiscriminate killing. Home collection and freezing of sputum will enable frequent and convenient assessment of P. aeruginosa population dynamics in CF.