The sensitivity of contrast-enhanced MR first pass perfusion imaging in detection and quantification of hypoperfused myocardium was evaluated using an instrumented, closed-chest dog model where graded regional hypoperfusion was induced by applying predetermined levels of stenosis to the left anterior descending artery (LAD). All measurements were performed at rest and under stress induced by dipyridamole (DIP). Myocardial perfusion was assessed both with MR and radiolabeled microspheres injected immediately before the administration of the MR contrast agent. Ultrafast MR imaging was performed using a Turbo FLASH sequence with a 180 degrees inversion prepulse. A Gd-DTPA bolus was injected into the left atrium and T1-weighted images were acquired with every heart beat. Signal intensity measured from the images in regions of the LAD and left circumflex (LCx) perfusion beds was plotted against time to generate signal intensity versus time curves (SI time curve). Various flow indices were derived according to the indicator dilution theory, and compared with and without volume correction due to vasodilation to the myocardial blood flow (MBF) calculated from radiolabeled microspheres. Correlation of the MR and MBF data demonstrated that different transmural and regional myocardial perfusion levels can be easily visualized in the perfusion images and accurately monitored by the SI time curves. Detection of the impairment of myocardial perfusion improved significantly after administration of DIP. The inverse mean transit time calculated from the SI time curve was found to yield a linear correlation to absolute MBF derived from the microsphere data. These results suggest that with intracardiac injections of exogenous contrast agent, myocardial perfusion can be assessed parametrically with first pass contrast enhanced ultrafast MRI.

Objectives: Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) pose a significant threat, requiring appropriate initial therapy to optimize patient outcomes. Ceftolozane/tazobactam (C/T), a novel cephalosporin in combination with a beta-lactamase inhibitor, has been evaluated in a Phase-3 clinical trial within a HABP/VABP population. The objective of this analysis was to obtain the relative treatment effect of C/T versus relevant comparators for the treatment of HABP/VABP. Methods: A systematic literature review was conducted (EMBASE®, MEDLINE®, Cochrane) to identify English language RCTs published from 2000 onwards for C/T or comparators for the treatment of gram-negative HABP/VABP. Outcomes included clinical response (CR), microbiological response (MR), and all-cause mortality as per the clinically evaluable (CE), microbiologically evaluable (ME), and intention-to-treat populations (ITT), respectively. The efficacy of C/T vs. comparators was estimated using network metaanalysis (NMA), and naïve indirect treatment comparison (NITC). Results: Of the 1582 citations retrieved, 22 unique studies describing 18 antibiotics were included in the analyses. The evidence-base was heterogeneous in terms of: study date, disease severity, % ventilated patients, population-and outcome-definitions; with a non-inferiority trial design observed most commonly. Results of the NMA showed no significant differences between C/T and any comparator for CR (CE and ITT population) or all-cause mortality (ITT population) in the available populations. C/T was estimated to be statistically superior to ceftazidime+amikacin for MR only, and was numerically comparable to all other comparators in the ME population available. NITC result showed C/T was comparable vs. all interventions, across all outcomes. Conclusions: The SLR and multi-treatment comparison results indicate the comparable efficacy of C/T with relevant comparators for the treatment of HABP/VABP; they also highlight the challenges faced within this heterogeneous evidence-base, often informed by a single trial which can mask any meaningful differences in the underlying severity-of-illness and ventilation status of the population.

No abstract

No abstract