UCP1-dependent brown adipose activation accelerates cardiac metabolic remodeling and reduces initial hypertrophic and fibrotic responses to pathological stress.

Brown adipose tissue (BAT) is correlated to cardiovascular health in rodents and humans, but the physiological role of BAT in the initial cardiac remodeling at the onset of stress is unknown. Activation of BAT via 48 h cold (16°C) in mice following transverse aortic constriction (TAC) reduced cardiac gene expression for LCFA uptake and oxidation in male mice and accelerated the onset of cardiac metabolic remodeling, with an early isoform shift of carnitine palmitoyltransferase 1 (CPT1) toward increased CPT1a, reduced entry of long chain fatty acid (LCFA) into oxidative metabolism (0.59 ± 0.02 vs. 0.72 ± 0.02 in RT TAC hearts, p < .05) and increased carbohydrate oxidation with altered glucose transporter content. BAT activation with TAC reduced early hypertrophic expression of ß-MHC by 61% versus RT-TAC and reduced pro-fibrotic TGF-ß1 and COL3α1 expression. While cardiac natriuretic peptide expression was yet to increase at only 3 days TAC, Nppa and Nppb expression were elevated in Cold TAC versus RT TAC hearts 2.7- and 2.4-fold, respectively. Eliminating BAT thermogenic activation with UCP1 KO mice eliminated differences between Cold TAC and RT TAC hearts, confirming effects of BAT activation rather than autonomous cardiac responses to cold. Female responses to BAT activation were blunted, with limited UCP1 changes with cold, partly due to already activated BAT in females at RT compared to thermoneutrality. These data reveal a previously unknown physiological mechanism of UCP1-dependent BAT activation in attenuating early cardiac hypertrophic and profibrotic signaling and accelerating remodeled metabolic activity in the heart at the onset of cardiac stress.

Magnetic Resonance Imaging Availability Reduces Computed Tomography Use for Pediatric Appendicitis Diagnosis.

OBJECTIVES: To determine if introducing magnetic resonance imaging (MRI) as an imaging option for children with suspected appendicitis and an inconclusive ultrasound reduces computed tomography (CT) use. METHODS: This is a retrospective cohort study of patients aged 5 to 18 years who presented to a pediatric emergency department (ED) with suspected appendicitis. Rates of CT use 1 year before and 1 year after MRI availability are compared. Secondary outcomes include missed and negative appendectomies, imaging charges, time to antibiotics and surgery, time to radiology read, ED length of stay, and test characteristics of MRI and CT. RESULTS: Of the 981 patients screened, 499 patients met inclusion criteria. There was an absolute reduction of CT use of 25% from 38% in year 1 to 13% in year 2 (95% confidence interval, 18% to 33%). Advanced imaging charges were $371 higher in year 2 (MRI) than year 1 (CT), and median time to radiologist reads was longer in MRIs than CTs (129 versus 62 minutes; difference 53 minutes, 95% confidence interval, 23 to 74 minutes). All other secondary outcomes, including ED length of stay and test characteristics, were statistically similar. CONCLUSIONS: Introducing MRI for as an imaging option for children with suspected appendicitis and an inconclusive ultrasound markedly reduced CT use, but did result in a small increase in imaging charges and time to preliminary radiology read.

Use of Pulmonary Computed Tomography for Evaluating Suspected Stroke-Associated Pneumonia.

OBJECTIVES: Accurate and timely diagnosis of pneumonia complicating stroke remains challenging and the diagnostic accuracy of chest X-ray (CXR) in the setting of stroke-associated pneumonia (SAP) is uncertain. The overall objective of this study was to evaluate the use of pulmonary computed tomography (CT) in diagnosis of suspected SAP. MATERIALS AND METHODS: Patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH) were recruited within 24h of clinically suspected SAP and underwent non-contrast pulmonary CT within 48h of antibiotic initiation. CXR and pulmonary CT were reported by two radiologists. Pulmonary CT was used as the reference standard for final diagnosis of SAP. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and diagnostic odds ratio (OR) for CXR were calculated. RESULTS: 40 patients (36 IS, 4 ICH) with a median age of 78y (range 44y-90y) and a median National Institute of Health Stroke Scale score of 13 (range 3-31) were included. All patients had at least one CXR and 35/40 patients (88%) underwent pulmonary CT. Changes consistent with pneumonia were present in 15/40 CXRs (38%) and 12/35 pulmonary CTs (34%). 9/35 pulmonary CTs (26%) were reported normal. CXR had a sensitivity of 58.3%, specificity of 73.9%, PPV of 53.8 %, NPV of 77.2 %, diagnostic OR of 3.7 (95% CI 0.7 - 22) and an accuracy of 68.5% (95% CI 50.7% -83.1%). DISCUSSION: CXR has limited diagnostic accuracy in SAP. The majority of patients started on antibiotics had no evidence of pneumonia on pulmonary CT with potential implications for antibiotic stewardship. CONCLUSIONS: Pulmonary CT could be applied as a reference standard for evaluation of clinical and biomarker diagnostic SAP algorithms in multi-center studies.