How Three Self-Secreted Biofilm Exopolysaccharides of Pseudomonas aeruginosa, Psl, Pel, and Alginate, Can Each Be Exploited for Antibiotic Adjuvant Effects in Cystic Fibrosis Lung Infection.

In cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to their failure to eradicate infection but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of P. aeruginosa, wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. The three biofilm-associated EPSs secreted by P. aeruginosa (alginate, Psl, and Pel) are each under investigation and are being exploited in ways that potentiate antibiotics. In this review, we describe the development and structure of P. aeruginosa biofilms before examining each EPS as a potential therapeutic target for combating pulmonary infection with P. aeruginosa in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

ACR appropriateness criteria imaging of mediastinal masses

Mediastinal masses can present with symptoms, signs, and syndromes or incidentally. Selecting the appropriate diagnostic imaging study for mediastinal mass evaluation requires awareness of the strengths and weaknesses of the various imaging modalities with regard to tissue characterization, soft tissue contrast, and surveillance. This publication expounds on the differences between chest radiography, CT, PET/CT, ultrasound, and MRI in terms of their ability to decipher and surveil mediastinal masses. Making the optimal imaging choice can yield diagnostic specificity, avert unnecessary biopsy and surgery, guide the interventionist when necessary, and serve as a means of surveillance for probably benign, but indeterminate mediastinal masses. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Improved visualization of the coronary arteries using motion correction during vasodilator stress CT myocardial perfusion imaging.

BACKGROUND: Vasodilator stress computed tomography perfusion (sCTP) imaging is complementary to coronary CT angiography (CCTA), used to determine the hemodynamic significance of coronary artery disease. However, it requires a separate image acquisition due to motion artifacts caused by higher heart rates during stress, resulting in increased iodine contrast dose and radiation. We sought to determine whether a novel motion correction algorithm applied to stress images would improve the visualization of the coronary arteries to potentially allow CCTA + sCTP evaluation in a single scan. METHODS: 28 patients referred for clinically indicated CCTA (iCT, Philips) underwent sCTP imaging (retrospective-gating with dose modulation; 100 kVp and 250 mA; 5.2 ± 4.3 mSv) after regadenoson (0.4 mg, Astellas). Stress images were reconstructed using standard filtered back-projection (FBP) and also processed to generate interaction-free coronary motion-compensated back-projection reconstructions (MCR). Each coronary artery from standard FBP and MCR images was viewed side-by-side by a reader blinded to the reconstruction technique, who graded severity of motion artifact by segment (scale 0-5, with 3 as the threshold for diagnostic quality) and to measure signal-to-noise and contrast-to-noise ratios (SNR, CNR). RESULTS: Visualization scores were higher with MCR for all coronary segments, including 14/86 (16%) segments deemed as non-diagnostic on FBP images. SNR (7 ± 2) and CNR (15 ± 8) were unchanged by motion-correction (7 ± 3, p = 0.88 and 15 ± 5, p = 0.94, respectively). CONCLUSIONS: MCR improves the visualization of coronary anatomy on sCTP images without degrading image characteristics. This algorithm is an important step towards the combined assessment of coronary anatomy and myocardial perfusion in a single scan, which will reduce study time, radiation exposure and contrast dose.

Association Between Skin and Aortic Vascular Inflammation in Patients With Psoriasis: A Case-Cohort Study Using Positron Emission Tomography/Computed Tomography.

Importance: Inflammation is critical in the development of atherosclerosis. Psoriasis is a chronic inflammatory skin disease that is associated with increased vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography in vivo and future cardiovascular events. It provides a human model to understand the effect of treating inflammation in a target organ (eg, the skin) on vascular diseases. Objective: To investigate the association between change in skin disease severity and change in vascular inflammation at 1 year and to characterize the impact of 1 year of anti-tumor necrosis factor therapy on vascular inflammation. Design, Setting, and Participants: In this prospective cohort study, 220 participants from outpatient practices were recruited at the US National Institutes of Health. A total of 115 consecutively recruited patients with psoriasis were followed up at 1 year. The study was conducted from January 1, 2013, through October 31, 2016, with data analyzed in November 2016. Exposure: Skin inflammation measured as Psoriasis Area and Severity Index (PASI) score. Main Outcomes and Measures: Vascular inflammation assessed as target-to-background ratio by 18fluorodeoxyglucose positron emission tomography/computed tomography. Results: Among the 115 patients, the mean (SD) age at 1-year follow-up was 50.8 (12.8) years and 68 were men (59%). The cohort had a low cardiovascular risk by Framingham risk score and mild-to-moderate psoriasis, with a median PASI score of 5.2 (interquartile range, 3.0-8.9). At follow-up, the total cohort had a median improvement in PASI score of 33%, with use of topical therapy (60%), biological therapy (66%, mostly anti-tumor necrosis factor) and phototherapy (15%) (P < .001). Moreover, improvement in PASI score was associated with improvement in target-to-background ratio of 6%, mainly driven by those with higher responses in PASI score (P < .001). This association persisted beyond traditional risk factors (ß = 0.19; 95% CI, 0.012-0.375; P = .03) and was the strongest in those initiated with anti-tumor necrosis factor therapy (ß = 0.79; 95% CI, 0.269-1.311; P = .03). Conclusions and Relevance: Improvement in psoriasis skin disease severity was associated with improvement in aortic vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography, with greater improvement in aortic vascular inflammation observed in those who had higher than 75% reduction in skin disease severity. These findings suggest that controlling remote target organ inflammation (eg, in the skin) may improve vascular diseases; however, randomized clinical trials are needed to confirm these findings.