CCTA in patients with positive troponin and low clinical suspicion for ACS: a useful diagnostic option to exclude obstructive CAD.

PURPOSE: It is uncertain whether patients with elevated troponin and non-classical presentation of acute coronary syndrome (ACS) should receive coronary CT angiography (CCTA). A proportion of these patients will have no coronary artery disease (CAD) and would benefit from non-invasive investigations and expedited discharge. Objectives were to determine most common diagnoses and rate of ACS among patients with positive troponin and low clinical suspicion of ACS who received CCTA. METHODS: IRB approved retrospective analysis of 491 consecutive patients in a level I trauma center ED referred for CCTA between April 4, 2015 to April 2, 2017. Patients were included if there was an elevated troponin (TnI > 0.045 µg/L) and atypical chest pain within 24 h prior to imaging. One hundred one patients met inclusion criteria; 17 excluded due to technical factors or history. Scans performed on dual-source CT. RESULTS: Eighty-four patients (47 men, 37 women) with median TnI of 0.11 ± 0.21 µg/L underwent CCTA 8.20 ± 6.41 h after first elevated Tn. Mean age was 53.2 ± 14.6 years. CCTA demonstrated absence of CAD in 39 patients (46.4%; 20 M, 19 F). CAD < 25% stenosis was observed in 24 (28.6%; 9 M, 15 F). CAD with 25-50% stenosis was observed in seven (8.3%; six M, one F). CAD > 50% stenosis was observed in 11 (13.1%; 9 M, 2 F), and non-diagnostic in three (3.6%, 3 M, 0 F). Forty-six (56.8%) were discharged directly from ED with median stay 15.82 ± 6.41 h. CONCLUSIONS: Use of CCTA in ED patients with elevated troponin and low clinical suspicion for ACS allowed obstructive CAD to be excluded in 83%.

Clinician modifiable factors associated with better quality of life in children with acquired brain injury undergoing rehabilitation.

OBJECTIVES: To identify clinician-modifiable factors related to quality of life (QOL) in children with acquired brain injury (ABI). PARTICIPANTS AND METHODS: Thirty-nine children attending an ABI rehabilitation program (5-18 years) were assessed using the Personality Inventory for Children-2, Vineland Adaptive Behavior Scale-2, Handicap-Related Problems for Parents Inventory and Children's Assessment of Participation and Enjoyment. The Pediatric Quality of Life Inventory was completed by children and parents six months later. RESULTS: Children with lower levels of internalising and externalising behaviours, health and social skill problems, and higher family functioning had significantly higher levels of total QOL (child and parent rated) (r = -.47 to -.79). In addition, children with higher levels of adaptive behaviour had significantly higher parent rated total QOL (r = .46). Measures of mother's stressors had moderate but not statistically significant relationships with the child's total QOL (r = -.31 to -.35). There were moderate and statistically significant relationships between measures of participation in physical activities and total QOL as rated by children (r = .42-.48) but not parents (r = .11-.30). CONCLUSIONS: These findings suggest potential targets to be investigated in future clinical research in rehabilitation following ABI in children to optimise QOL.

Unenhanced Dual-Energy Computed Tomography: Visualization of Brain Edema.

PURPOSE: The aim of this study was to determine whether dual-energy computed tomography (DECT) imaging is superior to conventional noncontrast computed tomography (CT) imaging for the detection of acute ischemic stroke. MATERIALS AND METHODS: This was a retrospective, single-center study of 40 patients who presented to the emergency department (ED) of a major, acute care, teaching center with signs and symptoms of acute stroke. Only those patients who presented to the ED within 4 hours of symptom onset were included in this study. All 40 patients received a noncontrast DECT of the head at the time of presentation. Each patient also received standard noncontrast CT of the head 24 hours after their initial presentation to the ED. "Brain edema" images were then reconstructed using 3-material decomposition with parameters adjusted to suppress gray/white matter contrast while preserving edema and increasing its conspicuity. The initial unenhanced, mixed images, brain edema, and 24-hour follow-up true noncontrast (TNC) images were reviewed and assigned Alberta Stroke Program Early CT scores. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Of the 40 patients, 28 (70%) were diagnosed with an acute infarction. Brain edema reconstructions were better able to predict end infarction volume, with Alberta Stroke Program Early CT scores similar to the 24-hour follow-up TNC CT (7.75 vs 7.7; P > 0.05), whereas the mixed images routinely underestimated the extent of infarction (8.975 vs 7.7; P < 0.001). Initial TNC images had a sensitivity, specificity, PPV, and NPV of 80% (95% confidence interval [CI], 51.9%-95.7%), 72.7% (95% CI, 39%-94%), 80% (95% CI, 51.9%-95.7%), and 72.73% (95% CI, 51.91%-95.67%), respectively. The DECT brain edema images provided a sensitivity, specificity, PPV, and NPV of 93.33% (95% CI, 68.05%-99.83%), 100% (95% CI, 71.51%-100%), 100% (95% CI, 76.84%-100%), and 91.67% (95% CI, 61.52%-99.79%), respectively. There was very good interrater reliability across all 3 imaging techniques. CONCLUSION: Brain edema reconstructions are able to more accurately detect edema and end-infarct volume as compared with initial TNC images. This provides a better assessment of the degree and extent of infarction and may serve to better guide therapy in the future.

Detection of Bone Marrow Edema in Nondisplaced Hip Fractures: Utility of a Virtual Noncalcium Dual-Energy CT Application.

Purpose To quantify the sensitivity and specificity of dual-energy computed tomographic (CT) virtual noncalcium images in the detection of nondisplaced hip fractures and to assess whether obtaining these images as a complement to bone reconstructions alters sensitivity, specificity, or diagnostic confidence. Materials and Methods The clinical research ethics board approved chart review, and the requirement to obtain informed consent was waived. The authors retrospectively identified 118 patients who presented to a level 1 trauma center emergency department and who underwent dual-energy CT for suspicion of a nondisplaced traumatic hip fracture. Clinical follow-up was the standard of reference. Three radiologists interpreted virtual noncalcium images for traumatic bone marrow edema. Bone reconstructions for the same cases were interpreted alone and then with virtual noncalcium images. Diagnostic confidence was rated on a scale of 1 to 10. McNemar, Fleiss κ, and Wilcoxon signed-rank tests were used for statistical analysis. Results Twenty-two patients had nondisplaced hip fractures and 96 did not have hip fractures. Sensitivity with virtual noncalcium images was 77% and 91% (17 and 20 of 22 patients), and specificity was 92%-99% (89-95 of 96 patients). Sensitivity increased by 4%-5% over that with bone reconstruction images alone for two of the three readers when both bone reconstruction and virtual noncalcium images were used. Specificity remained unchanged (99% and 100%). Diagnostic confidence in the exclusion of fracture was improved with combined bone reconstruction and virtual noncalcium images (median score: 10, 9, and 10 for readers 1, 2, and 3, respectively) compared with bone reconstruction images alone (median score: 9, 8, and 9). Conclusion When used as a supplement to standard bone reconstructions, dual-energy CT virtual noncalcium images increased sensitivity for the detection of nondisplaced traumatic hip fractures and improved diagnostic confidence in the exclusion of these fractures. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 17, 2017.

Novel riboswitch-binding flavin analog that protects mice against Clostridium difficile infection without inhibiting cecal flora.

Novel mechanisms of action and new chemical scaffolds are needed to rejuvenate antibacterial drug discovery, and riboswitch regulators of bacterial gene expression are a promising class of targets for the discovery of new leads. Herein, we report the characterization of 5-(3-(4-fluorophenyl)butyl)-7,8-dimethylpyrido[3,4-b]quinoxaline-1,3(2H,5H)-dione (5FDQD)-an analog of riboflavin that was designed to bind riboswitches that naturally recognize the essential coenzyme flavin mononucleotide (FMN) and regulate FMN and riboflavin homeostasis. In vitro, 5FDQD and FMN bind to and trigger the function of an FMN riboswitch with equipotent activity. MIC and time-kill studies demonstrated that 5FDQD has potent and rapidly bactericidal activity against Clostridium difficile. In C57BL/6 mice, 5FDQD completely prevented the onset of lethal antibiotic-induced C. difficile infection (CDI). Against a panel of bacteria representative of healthy bowel flora, the antibacterial selectivity of 5FDQD was superior to currently marketed CDI therapeutics, with very little activity against representative strains from the Bacteroides, Lactobacillus, Bifidobacterium, Actinomyces, and Prevotella genera. Accordingly, a single oral dose of 5FDQD caused less alteration of culturable cecal flora in mice than the comparators. Collectively, these data suggest that 5FDQD or closely related analogs could potentially provide a high rate of CDI cure with a low likelihood of infection recurrence. Future studies will seek to assess the role of FMN riboswitch binding to the mechanism of 5FDQD antibacterial action. In aggregate, our results indicate that riboswitch-binding antibacterial compounds can be discovered and optimized to exhibit activity profiles that merit preclinical and clinical development as potential antibacterial therapeutic agents.

Half-dose non-contrast CT in the investigation of urolithiasis: image quality improvement with third-generation integrated circuit CT detectors.

PURPOSE: The objective of this study is to establish the effect of third-generation integrated circuit (IC) CT detector on objective image quality in full- and half-dose non-contrast CT of the urinary tract. METHODS: 51 consecutive patients with acute renal colic underwent non-contrast CT of the urinary tract using a 128-slice dual-source CT before (n = 24) and after (n = 27) the installation of third-generation IC detectors. Half-dose images were generated using projections from detector A using the dual-source RAW data. Objective image noise in the liver, spleen, right renal cortex, and right psoas muscle was compared between DC and IC cohorts for full-dose and half-dose images reconstructed with FBP and IR algorithms using 1 cm(2) regions of interest. Presence and size of obstructing ureteric calculi were also compared for full-dose and half-dose reconstructions using DC and IC detectors. RESULTS: No statistical difference in age and lateral body size was found between patients in the IC and DC cohorts. Radiation dose, as measured by size-specific dose estimates, did not differ significantly either between the two cohorts (10.02 ± 4.54 mGy IC vs. 12.28 ± 7.03 mGy DC). At full dose, objective image noise was not significantly lower in the IC cohort as compared to the DC cohort for the liver, spleen, and right psoas muscle. At half dose, objective image noise was lower in the IC cohort as compared to DC cohort at the liver (21.32 IC vs. 24.99 DC, 14.7% decrease, p < 0.001), spleen (19.33 IC vs. 20.83 DC, 7.20% decrease, p = 0.02), and right renal cortex (20.28 IC vs. 22.98 DC, 11.7% decrease, p = 0.005). Mean obstructing ureteric calculi size was not significantly different when comparison was made between full-dose and half-dose images, regardless of detector type (p > 0.05 for all comparisons). CONCLUSIONS: Third-generation IC detectors result in lower objective image noise at full- and half-radiation dose levels as compared with traditional DC detectors. The magnitude of noise reduction was greater at half-radiation dose indicating that the benefits of using novel IC detectors are greater in low and ultra-low-dose CT imaging.

Assessment of sex differences in plaque morphology by coronary computed tomography angiography--are men and women the same?

PURPOSE: The objective of this study was to assess whether sex differences exist in plaque burden and plaque subtype as assessed by coronary computed tomography angiography (CCTA). METHODS: The study cohort included 937 consecutive patients who underwent CCTA between 2008 and 2010. Stenosis was quantified using the Society of Cardiovascular Computed Tomography stenosis grading scale and a total stenosis score (TSS) was generated. Plaque morphology (PM) was reported as predominantly calcified (CP), noncalcified (NCP), or mixed (MP) plaque, and CP, NCP, and MP percentages were calculated. RESULTS: On multivariate analysis, men were significantly more likely to have plaque (65.9% of men vs. 44.6% of women, p<0.001), at least one segment with ≥50% stenosis (22.7% of men vs. 10.3% of women, p<0.001) and higher TSS (mean score=2.81 for men vs. 1.58 for women, p<0.001). Sex was the strongest predictor in all models (odds ratio [OR]=2.55, 95% confidence interval [CI] 1.78-3.67, p<0.001 for any plaque; OR=2.48, 95% CI 1.48-4.16, p<0.01 for segments with ≥50% stenosis; ß=1.46, 95% CI 0.69-2.22, p<0.001 for TSS). Among patients with coronary plaque present, no significant sex differences in PM were found. CONCLUSIONS: Sex was the strongest risk factor for the presence and extent of plaque. Significant sex differences in PM did not exist.

Self-esteem, self-concept, and quality of life in children with hemiplegic cerebral palsy.

OBJECTIVES: To investigate self-esteem, self-concept and quality of life in children with hemiplegic cerebral palsy (HCP) compared with typically developing peers. STUDY DESIGN: Cross-sectional evaluation of 86 children (3-16 years; 54 boys; mean age 9.4 +/- 3.7 years) with HCP and age and sex-matched peers. Self-esteem/concept was measured with the Self-Perception Profile for Children (age 8-16; n = 55 pairs) and the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children (age 3-7 years; n = 31 pairs). Quality of life was measured with the Pediatric Quality of Life Inventory, version 4. RESULTS: Significant differences in mean scores ([95%CI] P < .05) favoring the peer group were found for physical competence (HCP 2.8 [2.5, 3.0]; peer 3.2 [3.1, 3.3]), athletic competence (HCP 2.7 [2.5, 2.9]; peer 3.1 [3.0, 3.3]), and scholastic competence (HCP 2.8 [2.6, 3.0]; peer 3.1 [3.0, 3.3]), but favored children with HCP for maternal acceptance (HCP 3.1 [2.9, 3.3]; peer 2.7 [2.5, 3.0]). Quality of life was significantly higher for the peer group for both parent (HCP 54.5 [51.1, 58.0]; peer 80.6 [78.3, 82.9]) and child (HCP 67.6 [62.7, 72.6]; peer 80.6 [78.1, 83.1]) scales. CONCLUSIONS: Children with HCP experience reduced quality of life and self-concept compared with typically developing peers.

Navigating the signalling network in mouse cardiac myocytes.

Cardiac myocytes have a complex network of signals that regulates their essential role in the rhythmic pumping of the heart. This network is an appealing model system in which to study the basic principles underlying cellular signalling mechanisms. Progress in this effort has come through the establishment of standardized myocyte isolation and culture procedures and characterization of important signalling responses.