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Transgenic tumour necrosis factor alpha (TNFα)-driven models of polyarthritis such as the TNFΔARE mouse have proven to be invaluable in delineating aspects of inflammatory disease pathophysiology in humans. Unfortunately, the onset of joint destruction and inflammation in these models represents a significant detriment to breeding management. We examined whether TNFα depleting therapy ‘infliximab’ might represent a significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNFΔARE males receiving either infliximab (10 mg/kg) or saline by twice-weekly intraperitoneal injection. Joint histology and bone morphology were assessed by histological analysis and micro-computed tomography (CT), respectively. Analysis of breeding was examined retrospectively in TNFΔARE males prior to, and following, regular introduction of infliximab. Clinical scores of inflammation were significantly reduced in TNFΔARE males receiving infliximab (control 6.6 arbitrary units [AU] ± 0.88 versus infliximab 4.4 AU ± 1.4; P

Objective Determine plaque subtype and volume difference in male and female patients with obstructive and non-obstructive CAD using 320-row MDCTA. Materials and methods 128 patients with suspected CAD underwent MDCTA. All studies were divided into two groups based on disease severity. 0–70% stenosis (non-obstructive CAD) & >70% (obstructive). All were compared for plaque quantity and subtypes by gender. Main arteries, RCA, LM, LAD and LCX were analyzed using Vitrea 5.2 software to quantify fatty, fibrous and calcified plaque. Thresholds for coronary plaque quantification (volume in mm3) were preset at 35 ± 12 HU for fatty, 90 ± 24 HU for fibrous and >130 HU for calcified/mixed plaque and analyzed using STATA software. Results Total plaque burden in 118 patients [65M: 53F] was significantly higher in all arteries in males compared to females with non-obstructive disease. Total plaque volume for males vs. females was: RCA: 10.10 ± 5.02 mm3 vs. 6.89 ± 2.75 mm3, respectively, p = 0.001; LAD: 7.21 ± 3.38 mm3 vs. 5.89 ± 1.93 mm3, respectively, p = 0.04; LCX: 9.13 ± 3.27 mm3 vs. 7.16 ± 1.73 mm3, respectively, p = 0.002; LM 15.13 ± 4.51 mm3 vs. 11.85 ± 4.03 mm3, respectively, p = 0.001. In sub-analyses, males had significantly more fibrous and fatty plaque in LM, LAD & LCX than females. However in the RCA, only fibrous plaque was significantly greater in males. Calcified plaque volume was not significantly different in both genders. Only 8% of patients had obstructive CAD (>70% stenosis); there was no significant difference in plaque volume or subtypes. Conclusion In patients with non-obstructive CAD, males were found to have significantly higher total coronary plaque volume with predominance of fibrous and fatty subtypes compared to females of the same age and BMI. There was no significant difference in plaque subtype or volume in patients with obstructive disease.

We investigated the association of electrocardiographic (ECG) abnormalities with markers of insulin resistance and pancreatic beta-cell dysfunction in a cross-sectional study of type 2 diabetes patients.Electrocardiographic criteria were evaluated in the Penn Diabetes Heart Study participants (n = 1671; 64% male; 61% Caucasian), including a sub-sample (n = 710) that underwent oral glucose tolerance testing. The Matsuda Insulin Sensitivity Index and homeostasis model assessment of insulin resistance (HOMA-IR) estimated insulin sensitivity; Insulinogenic Index and homeostasis model assessment of beta-cell function assessed beta-cell function. Multivariable regression modelling was used to analyse associations of ECG changes with these indices.In unadjusted analyses, subjects in the highest quartile of Matsuda index had the lowest prevalence of Q-waves (6.3% versus 15.3%, p = 0.005). In adjusted models, an inverse association was seen between Q-waves and log Matsuda index [one standard deviation increase; OR = 0.59 (95% CI 0.43-0.87 p = 0.001)]. In the full Penn Diabetes Heart Study, there was a direct association between Q-waves and HOMA-IR [one standard deviation increase; OR = 1.43 (95% CI 1.13-1.81, p = 0.003)]. In adjusted models, left ventricular hypertrophy also was inversely associated with Matsuda index and directly with HOMA-IR. Higher Insulinogenic Index scores were associated with a lower prevalence of nonspecific ST changes [OR = 0.78 (95% CI 0.62-0.98, p = 0.032)].In type 2 diabetic patients, both oral glucose tolerance testing-derived and HOMA-derived measures of insulin resistance were associated with pathologic Q-waves and left ventricular hypertrophy on ECGs. Copyright © 2016 John WileySons, Ltd.

To develop a simplified method to quantify liver fat using computed tomography (CT) fat % index (CTFPI) compared to liver spleen method (CTL/S, CTL-S).Noncontrast CT of the liver was performed in 89 patients (overweight, obese, severely obese) to quantify fat, using the following: CTFPI=[(65-patient HU)/65]×100, normal live r=65 HU.There was a strong linear correlation between CTFPI and the standard method of assessing liver fat using CTL/S (r=-0.901), CTL-S (r=-0.911). Hepatic HU and CTFPI were significantly different in the severely obese group compared to other two groups (P.05).Significant correlation indicates equal diagnostic accuracy of the two methods in appropriately calibrated scanners.

Purpose. To compare radiation dose and image quality using predefined narrow phase window versus complete phase window with dose modulation during R-R using 320-row MDCTA.Methods. 114 patients underwent coronary CTA study using 320-row MDCT scanner. 87 patients with mean age (61 + 13 years), mean BMI (29 + 6), and mean heart rate (HR) (58 + 7 bpm) were imaged at predefined 66–80% R-R interval and then reconstructed at 75% while 27 patients with mean age (63 + 16 years), mean BMI (28 + 5), and mean HR (57 + 7 bpm) were scanned throughout the complete R-R interval with tube current modulation. The effective dose (ED) was calculated from dose length product (DLP) and conversionk(0.014 mSv/mGy/cm). Image quality was assessed using a three-point ordinal scale (1 = excellent, 2 = good, and 3 = nondiagnostic).Results. Both groups were statistically similar to each other with reference of HR (P=0.59), BMI (P=0.17), and tube current mAs (P=0.68). The median radiation dose was significantly higher in those scanned with complete R-R phase window versus narrow phase window (P<0.0001). Independently of patient and scan parameters, increased phase window was associated with higher radiation dose (P<0.001). Image quality was better among those scanned with narrow phase window versus complete phase window (P<0.0001).Conclusion. Our study supports that good HR control and predefined narrow window acquisition result in lower radiation dose without compromising diagnostic image quality for coronary disease evaluation.

The aim of this study was to further explore the interplay between smoking status, coronary artery calcium (CAC), and all-cause mortality.Prior studies have not directly compared the relative prognostic impact of CAC in smokers versus nonsmokers. In particular, although a calcium score of zero (CAC = 0) is a known favorable prognostic marker, whether smokers with CAC = 0 have as good a prognosis as nonsmokers with CAC = 0 is unknown. Given that computed tomography (CT) screening for lung cancer appears effective in smokers, the relative prognostic implications of visualizing any CAC versus no CAC on such screening also deserve study.Our study cohort consisted of 44,042 asymptomatic individuals referred for noncontrast cardiac CT (age 54 ± 11 years, 54% men). Subjects were followed for a mean of 5.6 years. The primary endpoint was all-cause mortality.Approximately 14% (n = 6,020) of subjects were active smokers at enrollment. There were 901 deaths (2.05%) overall, with increased mortality in smokers versus nonsmokers (4.3% vs. 1.7%, p0.0001). Smoking remained a risk factor for mortality across increasing strata of CAC scores (1 to 100, 101 to 400, and400). At each stratum of elevated CAC score, mortality in smokers was consistently higher than mortality in nonsmokers from the CAC stratum above. In multivariable analysis within these strata, we found mortality hazard ratios of 3.8 (95% confidence interval [CI]: 2.8 to 5.2), 3.5 (95% CI: 2.6 to 4.9), and 2.7 (95% CI: 2.1 to 3.5), respectively, in smokers compared with nonsmokers. However, among the 19,898 individuals with CAC = 0, the mortality hazard ratio for smokers without CAC was 3.6 (95% CI: 2.3 to 5.7), compared with nonsmokers without CAC.Smoking is a risk factor for death across the entire spectrum of subclinical coronary atherosclerosis. Smokers with any CAC had significantly higher mortality than smokers without CAC, a finding with implications for smokers undergoing lung cancer CT-based screening. However, the absence of CAC might not be as useful a "negative risk factor" in active smokers, because this group has mortality rates similar to nonsmokers with mild-to-moderate atherosclerosis.

Background Non-cardiac findings (NCFs) are seen in more than a third of cardiac computed tomographic and cardiac magnetic resonance imaging studies. The prevalence and importance of NCFs in transthoracic echocardiographic (TTE) imaging is unknown. The aim of this study was to determine the prevalence of NCFs on TTE imaging. Methods The subcostal images of all comprehensive adult TTE studies performed at one institution in December 2008 were retrospectively reviewed for NCFs by a radiologist with fellowship training in cardiovascular and abdominal radiology and blinded to the TTE report findings and clinical histories. Additional TTE image orientations were assessed in a subset of 300 studies. NCFs were categorized as benign (e.g., simple hepatic cyst), indeterminate (e.g., ascites), or worrisome (e.g., liver metastases). If an indeterminate or worrisome NCF was identified, the patient's electronic medical record was reviewed to determine if the NCF was previously known. Results Of 1,008 TTE studies (443 inpatient, 565 outpatient) in 922 patients, 77 NCFs were identified in 69 patients (7.5%). These included 20 benign (26%), 52 indeterminate (67%), and five worrisome (7%) NCFs. Intermediate and worrisome NCFs were more common in inpatient TTE studies (9% vs 3% outpatient, P = .002). The additional views demonstrated 2% more NCFs. Record review demonstrated that 60% of worrisome and 67% of indeterminate NCFs were previously known. No unknown NCF ultimately led to a change in patient management. Conclusions Clinical TTE studies demonstrate NCFs in 7.5% of all patients, with an increased prevalence on inpatient studies. Although 75% of NCFs were potentially management changing, the majority of these were previously known and very unlikely to lead to management changes. Further study is needed to validate these findings in other populations and to assess their clinical impact.

The purpose of this study was to compare radiation dose and image quality of 320- and 64-MDCT angiography using prospective gating.One hundred seventy-four patients underwent 320-MDCT, and 95 patients underwent 64-MDCT. The scan parameters for 320-MDCT were 120 kVp, 400 mA, and gantry rotation of 350 milliseconds; the parameters for 64-MDCT were 120 kVp, 600 mA, and gantry rotation of 350 milliseconds. Effective dose (ED) was calculated from the dose-length product and a conversion factor (k = 0.014 mSv / mGy × cm). Two observers independently assessed image quality using a 3-point scale, where 3 denotes excellent quality and 1 denotes nondiagnostic quality, using a 16-segment model. Discrepancies were settled by consensus.The ED was significantly lower in patients undergoing 320-MDCT angiography, with a median ED of 4.4 mSv (interquartile range [IQR], 3.4-6.2 mSv), compared with 64-MDCT angiography, with a median ED of 6.2 mSv (IQR, 5.5-6.9 mSv) (p = 0.0001). In patients with a heart rate of 65 beats/min or less (92%), the median radiation dose using 320-MDCT was 4.1 mSv (IQR, 3.2-6.1 mSv), and that for 64-MDCT angiography was 6.2 mSv (IQR, 5.8-6.9 mSv) (p = 0.0001). In patients with heart rate greater than 65 beats/min (8%), the median dose was higher with 320-MDCT (8.7 mSv; IQR, 5.9-14.3 mSv) than with 64-MDCT (5.8 mSv; IQR, 5.3-6.7 mSv) (p = 0.02). Segmental image quality was significantly better for 320-MDCT (excellent or good quality, 96.66%; nondiagnostic quality, 0.1%) than for 64-MDCT angiography (excellent or good quality, 86%; nondiagnostic quality, 3.33%) (all p0.0001).Image quality was good for both 320- and 64-MDCT angiography. Overall radiation dose was significantly lower in 320-MDCT angiography when the heart rate was 65 beats/min or less. Every effort should be made to control heart rate to minimize radiation dose.

The purpose of this study was to evaluate the relation between radiation dose reduction and volume scan length for prospectively ECG-gated 320-MDCT angiography in the diagnosis of coronary artery disease.MDCT with prospective ECG gating was performed at one of the three volume scan lengths depending on heart length. Of 175 patients, 95 (55%; body mass index, 29 ± 5.9; mean heart rate, 59 ± 7 beats/min) underwent scanning at 160 mm; 46 (26%; body mass index, 30 ± 4.1; mean heart rate, 56 ± 5.74 beats/min) at 140 mm; and 34 (19%; body mass index, 30 ± 3.71; mean heart rate, 58 ± 3.96 beats/min) at 120 mm.The median radiation doses were 6.5 mSv (95% CI, 6.03-7.2 mSv) for the 95 patients who underwent scanning at a volume scan length of 160 mm, 4.33 mSv (95% CI, 4.06-6.62 mSv) for the 46 patients who underwent scanning at 140 mm, and 3.47 mSv (95% CI, 3.15-3.62 mSv) for the 34 patients who underwent scanning at 120 mm. The reduction in scan length from 160 to 140 mm represented a reduction in scan length of 12.5% and the reduction to 120 mm a reduction of 25%. The median radiation dose was reduced 33% when volume scan length was changed to 140 mm and 47% when the length was changed to 120 mm.Dose optimization remains an important concern in cardiac CT, and for 320-MDCT angiography, substantial dose reduction can be achieved by reducing volume scan length so that it is in concert with the patient's heart length.

The purpose of this article is to estimate the absorbed radiation dose in radiosensitive organs during coronary MDCT angiography using 320-MDCT and to determine the effects of tube voltage variation and heart rate (HR) control on absorbed radiation dose.Semiconductor field effect transistor detectors were used to measure absorbed radiation doses for the thyroid, midbreast, breast, and midlung in an anthropomorphic phantom at 100, 120, and 135 kVp at two different HRs of 60 and 75 beats per minute (bpm) with a scan field of view of 320 mm, 400 mA, 320 × 0.5 mm detectors, and 160 mm collimator width (160 mm range). The paired Student's t test was used for data evaluation.At 60 bpm, absorbed radiation doses for 100, 120, and 135 kVp were 13.41 ± 3.59, 21.7 ± 4.12, and 29.28 ± 5.17 mGy, respectively, for midbreast; 11.76 ± 0.58, 18.86 ± 1.06, and 24.82 ± 1.45 mGy, respectively, for breast; 12.19 ± 2.59, 19.09 ± 3.12, and 26.48 ± 5.0 mGy, respectively, for lung; and 0.37 ± 0.14, 0.69 ± 0.14, and 0.92 ± 0.2 mGy, respectively, for thyroid. Corresponding absorbed radiation doses for 75 bpm were 38.34 ± 2.02, 59.72 ± 3.13, and 77.8 ± 3.67 mGy for midbreast; 26.2 ± 1.74, 44 ± 1.11, and 52.84 ± 4.07 mGy for breast; 38.02 ± 1.58, 58.89 ± 1.68, and 78 ± 2.93 mGy for lung; and 0.79 ± 0.233, 1.04 ± 0.18, and 2.24 ± 0.52 mGy for thyroid. Absorbed radiation dose changes were significant for all organs for both tube voltage reductions as well as for HR control from 75 to 60 bpm at all tube voltage settings (p0.05). The absorbed radiation doses for the calcium score protocol were 11.2 ± 1.4 mGy for midbreast, 9.12 ± 0.48 mGy for breast, 10.36 ± 1.3 mGy for lung, and 0.4 ± 0.05 mGy for thyroid.CT angiography with 320-MDCT scanners results in absorbed radiation doses in radiosensitive organs that compare favorably to those previously reported. Significant dose reductions can be achieved by tube voltage reductions and HR control.

Plasma C-reactive protein (CRP) is associated with cardiovascular disease (CVD), but effects may vary by gender and degree of CVD risk. Whether CRP has value as a CVD risk marker in type-2 diabetes (T2DM) is unclear. We examined whether CRP has gender differences in association with coronary artery calcium (CAC) in diabetic and nondiabetic samples without clinical CVD.We performed cross-sectional analyses of gender influence on CRP association with CAC in the Penn Diabetes Heart Study (N = 1299 with T2DM), the Study of Inherited Risk of Coronary Atherosclerosis (N = 860 nondiabetic subjects) and a combined sample.Female gender was associated with higher plasma CRP in diabetic and nondiabetic samples after adjustment for covariates. There was a strong interaction by gender in the association of CRP with CAC (interaction P0·001). In diabetic women, CRP was associated with higher CAC even after further adjustment for age, race, medications, metabolic syndrome, Framingham risk score and body mass index [Tobit ratio 1·60, 95% CI (1·03-2·47)]. Although this relationship was attenuated in nondiabetic women, the combined sample maintained this association in fully adjusted models [1·44, 95% CI (1·13-1·83)]. There was no association of CRP with CAC in either diabetic or nondiabetic men.CRP may be a useful marker of cardiovascular risk in women, particularly in diabetic women who otherwise have no known CVD. Prospective studies are needed to better assess the gender differences in CRP utility and the use of CRP in T2DM.

Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as coronary artery calcium (CAC). Although CAC is an established predictor of cardiovascular events, limited evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing electron beam computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. Multivariate Cox regression models were developed to predict all-cause mortality according to the presence of AVC. A total of 517 patients (6%) had AVC on electron beam computed tomography. During follow-up, 124 patients died (1.5%), for an overall survival rate of 96.1% and 98.7% for those with and without AVC, respectively (hazard ratio 3.39, 95% confidence interval 2.09 to 5.49). After adjustment for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking, and a family history of premature coronary heart disease, AVC remained a significant predictor of mortality (hazard ratio 1.82, 95% confidence interval 1.11 to 2.98). Likelihood ratio chi-square statistics demonstrated that the addition of AVC contributed significantly to the prediction of mortality in a model adjusted for traditional risk factors (chi-square = 5.03, p = 0.03) as well as traditional risk factors plus the presence of CAC (chi-square = 3.58, p = 0.05). In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC.