Inflammation and Hypervascularization in a Large Animal Model of Knee Osteoarthritis: Imaging with Pathohistologic Correlation.

PURPOSE: To evaluate if synovial inflammation and hypervascularization are present in a dog model of knee osteoarthritis and can be detected on conventional magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), contrast-enhanced magnetic resonance imaging (CE-MRI), and quantitative digital subtraction angiography (Q-DSA) imaging. MATERIALS AND METHODS: Six dogs underwent MRI and angiography of both knees before and 12 weeks after right knee anterior cruciate ligament injury. Synovial vascularity was evaluated on CE-MRI, DCE-MRI, and Q-DSA by 2 independent observers. Synovial inflammation and vascularity were histologically scored independently. Cartilage lesions and osteophytes were analyzed macroscopically, and cartilage volumetry was analyzed by MRI. Vascularity and osteoarthritis markers on imaging were compared before and after osteoarthritis generation, and between the osteoarthritis model and the control knee, using linear mixed models accounting for within-dog correlation. RESULTS: In all knees, baseline imaging showed no abnormalities. Control knees did not develop significant osteoarthritis changes, synovial inflammation, or hypervascularization. In osteoarthritis knees, mean synovial enhancement score on CE-MR imaging increased by 13.1 ± 0.59 (P < .0001); mean synovial inflammation variable increased from 47.33 ± 18.61 to 407.97 ± 18.61 on DCE-MR imaging (P < .0001); and area under the curve on Q-DSA increased by 1058.58 ± 199.08 (P = .0043). Synovial inflammation, hypervascularization, and osteophyte formations were present in all osteoarthritis knees. Histology scores showed strong correlation with CE-MR imaging findings (Spearman correlation coefficient [SCC] = 0.742; P = .0002) and Q-DSA findings (SCC = 0.763; P < .0001) and weak correlation with DCE-MR imaging (SCC = -0.345; P = .329). Moderate correlation was found between CE-MR imaging and DSA findings (SCC = 0.536; P = .0004). CONCLUSIONS: In this early-stage knee osteoarthritis dog model, synovial inflammation and hypervascularization were found on imaging and confirmed by histology.

Detection of Steatohepatitis in a Rat Model by Using Spectroscopic Shear-Wave US Elastography.

Purpose To compare low- versus high-frequency ultrasonographic (US) elastography for detection of steatohepatitis in rats by using histopathologic findings as the reference standard. Materials and Methods Between March and September 2014, after receiving approval from the institutional animal care committee, 60 male Sprague-Dawley rats were fed either a standard chow for 4 weeks or a methionine- and choline-deficient diet for 1, 4, 8, or 12 weeks to induce a continuum of steatohepatitis severity. Liver shear stiffness was assessed in vivo by using US elastography at low (40-130-Hz) and high (130-220-Hz) frequencies. Histologic features (steatosis, inflammation, and fibrosis) and modified nonalcoholic steatohepatitis categories were used as reference standards. Definite steatohepatitis was divided into steatohepatitis with fibrosis stage 1 or lower and stage 2 and higher. Analyses included the Kendall τ correlation, multivariable linear regression analyses, Kruskal-Wallis rank sum test, and post hoc Dunn test with Holm correction. Results Correlations between liver shear stiffness and histologic features were higher at high frequencies than at low frequencies (low frequency: 0.08, 0.24, and 0.20 for steatosis, inflammation, and fibrosis, respectively; high frequency: 0.11, 0.35, and 0.50, respectively). The absolute value of multivariable regression coefficients was higher at high frequencies for the presence of steatosis, inflammation grade, and fibrosis stage (low frequency: -0.475, 0.157, and 0.209, respectively; high frequency: -0.893, 0.357, and 0.447, respectively). The model fit was better at high frequencies (adjusted R2 = 0.57) than at low frequencies (adjusted R2 = 0.21). There was a significant difference between steatohepatitis categories at both low and high frequencies (P = .022 and P < .001, respectively). Conclusion Liver shear stiffness measured with US elastography provided better distinction of steatohepatitis categories at high frequencies than at low frequencies. Further, liver shear stiffness decreased with steatosis and increased with inflammation and fibrosis at both low and high frequencies. © RSNA, 2016 Online supplemental material is available for this article.

Stabilization of renal function after the first year of follow-up in kidney transplant recipients treated for significant BK polyomavirus infection or BK polyomavirus-associated nephropathy.

BACKGROUND: BK polyomavirus virus (BKPyV) screening and immunosuppression reduction effectively prevent graft loss due to BKPyV-associated nephropathy (BKPVAN) during the first year after transplantation. The aim of our study was to evaluate the impact of this infection during longer follow-up periods. METHODS: We reviewed the outcome of our screening and immunosuppression reduction protocol in 305 patients who received a kidney transplant between March 2008 and January 2013. Quantitative BKPyV DNA surveillance in plasma was performed at 1, 2, 3, 6, 9, and 12 months after transplantation. Patients with significant viremia and/or biopsy-proven BKPVAN were treated with immunosuppression reduction and leflunomide. RESULTS: During the first post-transplant year, 24 patients (7.9%) developed significant viremia at a median time of 95 days, and 18 patients had BKPVAN; 23 of the 24 (7.5%) were treated according to our protocol (group BKV+); 225 patients (73.8%) did not develop any BK viremia (group BKV-). Allograft function was similar in both groups at 1 month post transplantation (P=.87), but significantly worse at 1 year in the BKV+ group (P=.002). Thereafter, kidney function stabilized in the BKV+ group and no differences in patient and graft survival were seen between the groups after a median follow-up of 4 years. CONCLUSIONS: We confirm the early occurrence of BKPyV replication after transplantation and the short-term decline in renal function. However, early detection of BKPyV replication, prompt diagnosis, and reduction in immunosuppression may offer long-term benefits for graft function.

Neutrophil count is associated with survival in localized prostate cancer.

BACKGROUND: Increasing evidence suggests a close relationship between systemic inflammation and cancer development and progression. The neutrophil to lymphocyte ratio (NLR) has been shown to be an independent prognostic indicator in various advanced and localized cancers. We investigated the influence of markers of systemic inflammation such as leucocyte counts and metabolic co-morbidities on overall survival (OS) after radiotherapy for localized prostate cancer. METHODS: We conducted a retrospective study of patients with localized prostate cancer treated with definitive external beam radiotherapy or brachytherapy. Univariate and multivariate cox proportional hazards models were used to investigate the influence of the following factors on OS: age, neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), Cancer of the Prostate Risk Assessment (CAPRA) score as well as comorbidities associated with inflammation such as cardiac history, diabetes and use of a statin. A stepwise selection of variable based on the Akaike information criterion (AIC) was used for multivariate analysis. RESULTS: In total, 1772 pts were included; blood count data was available for 950 pts. Median age was 68 years (44-87). Actuarial 5 years OS and biochemical recurrence-free survival (BRFS) for the 1772 patients were 93% and 95%, respectively, with a median follow-up of 44 months (1-156). On univariate analysis, neutrophil count (p = 0.04), cardiac history (p = 0.008), age (p = 0.001) and CAPRA (p = 0.0002) were associated with OS. Lymphocytes, NLR and comorbidities other than cardiac history were not associated with mortality. On multivariate analysis, neutrophil count (HR = 1.18, 95 % CI: 1.017-1.37, p = 0.028), age (HR = 1.06, 95 % CI: 1.01-1.1, p = 0.008) and CAPRA (HR = 1.16, 95 % CI: 1.03-1.31, p = 0.015) were independent predictors of OS. CONCLUSION: Neutrophil count, as a possible marker of systemic inflammation, appear to be an independent prognostic factor for overall mortality in localized prostate cancer. A validation cohort is needed to corroborate these results.

Association of epicardial fat with noncalcified coronary plaque volume and with low attenuation plaque in people with HIV.

OBJECTIVES: People with HIV are exposed to a higher risk of coronary artery disease (CAD) compared with the general population. Epicardial fat may play a unique role in promoting coronary atherosclerosis. We measured epicardial fat in participants living with HIV and controls and investigated its association with coronary plaque volume and low attenuation plaque, a marker of plaque vulnerability. DESIGN: This is a cross-sectional study, nested in the Canadian HIV and Aging Cohort Study, a large prospective cohort actively following participants with HIV and controls. Participants with low/intermediate cardiovascular risk without symptoms/history of CAD were invited to undergo cardiac computed tomography (CT). METHODS: Volume of epicardial fat, coronary plaque and low attenuation component of the plaque were measured. Association between epicardial fat, coronary plaque volume and low attenuation component was tested using adjusted regression analysis. RESULTS: A total of 169 participants with HIV and 81 controls underwent cardiac CT. Participants with HIV had a greater epicardial fat volume compared with controls (P = 0.019). In participants with HIV, epicardial fat volume was positively associated with duration of nonnucleoside reverse transcriptase inhibitors (NNRTI) (ß=2.19, P = 0.004). After adjustment for cardiovascular risk factors, epicardial fat volume was positively associated to noncalcified plaque volume [odds ratio (OR) = 1.09, P = 0.028] and to the low-attenuation plaque component portion (ß=0.38, P = 0.026). CONCLUSION: The association of epicardial fat volume to noncalcified plaque volume and to low attenuation component plaque may suggest a potential mechanism by which epicardial fat could be a silent driver of CAD in the HIV population.

LI-RADS for CT diagnosis of hepatocellular carcinoma: performance of major and ancillary features.

PURPOSE: To evaluate the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) v2017 major features, the impact of ancillary features, and categories on contrast-enhanced computed tomography (CECT) for the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 59 patients (104 observations including 72 HCCs) with clinical suspicion of HCC undergoing CECT between 2013 and 2016. Two radiologists independently assessed major and ancillary imaging features for each liver observation and assigned a LI-RADS category based on major features only and in combination with ancillary features. The composite reference standard included pathology or imaging. Per-lesion estimates of diagnostic performance of major features, ancillary features, and LI-RADS categories were assessed by generalized estimating equation models. RESULTS: Major features (arterial phase hyperenhancement, washout, capsule, and threshold growth) respectively had a sensitivity of 86.1%, 81.6%, 20.7%, and 26.1% and specificity of 39.3%, 67.9%, 89.9%, and 85.0% for HCC. Ancillary features (ultrasound visibility as discrete nodule, subthreshold growth, and fat in mass more than adjacent liver) respectively had a sensitivity of 42.6%, 50.8%, and 15.1% and a specificity of 79.2%, 66.9%, and 96.4% for HCC. Ancillary features modified the final category in 4 of 104 observations. For HCC diagnosis, categories LR-3, LR-4, LR-5, and LR-TIV (tumor in vein) had a sensitivity of 5.3%, 29.0%, 53.7%, and 10.7%; and a specificity of 49.1%, 84.4%, 97.3%, and 96.4%, respectively. CONCLUSION: On CT, LR-5 category has near-perfect specificity for the diagnosis of HCC and ancillary features modifies the final category in few observations.

Shear wave elasticity imaging for residual endoleak and thrombus characterisation after endoleak embolisation following endovascular aneurysm repair: a canine animal study.

BACKGROUND: To evaluate residual endoleak and thrombus organisation with shear wave imaging (SWI) after endoleak embolisation through an animal study. METHODS: This prospective experimental study involved eight dogs with creation of 16 iliac aneurysms and type I endoleak after endovascular aneurysm repair (EVAR). Embolisation agents were injected into the sac to seal endoleak. SWI and colour flow Doppler ultrasound (DUS) were performed at implantation, one week, and one and three months after implantation; for three dogs, SWI and DUS were also performed six months after implantation. Digital subtraction angiography and contrast-enhanced computed tomography were performed at sacrifice. Macroscopic and histopathological analyses were processed to identify regions of interest (ROIs) for endoleak, fresh thrombus, organised thrombus and embolisation agent, where SWI elasticity moduli were compared. RESULTS: At sacrifice, nine aneurysms had residual endoleak, while seven were sealed. Ten had a fresh and 15 had an organised thrombus. SWI was able to detect all endoleaks, including two cases undetected with DUS. Elasticity moduli of 0.2 kPa ± 0.1 kPa (mean ± SD), 9.5 kPa ± 3.3 kPa, 48.1 kPa ± 21.3 kPa and 44.9 kPa ± 23.7 kPa were found in the ROIs positioned in endoleaks, fresh thrombi, organised thrombi and embolisation agent, respectively. Elasticity values of endoleak and fresh thrombus were lower than those of organised thrombi and embolisation agent (p < 0.001). Stiffness of fresh thrombus at one week (8.7 kPa ± 3.6 kPa) increased at three months (30.2 kPa ± 13.8 kPa), indicating thrombus maturation (p < 0.001). CONCLUSIONS: In a dog model of iliac EVAR, SWI was able to identify endoleak, thrombus maturation and embolising agents after endoleak embolisation.

Anxiety, depression and PTSD-related symptoms in spouses and close relatives of burn survivors: When the supporter needs to be supported.

OBJECTIVES: The aim of the study was to assess the prevalence of anxiety, depression and PTSD-related symptoms reported by spouses and close relatives of adult burn survivors. Potential associations between these symptoms and variables such as the severity of the burn were also explored. METHOD: Participants were spouses (n=31) and close relatives (n=25) of hospitalized patients with acute burns. Anxiety and depression symptoms were assessed by the Hospital Distress Anxiety and Depression Scale and PTSD-related symptoms by the Modified PTSD Symptom Scale at both admission to and discharge from the burn unit. RESULTS: At admission, 77% of spouses and 56% of close relatives of burn patients reported anxiety, depression or PTSD-related symptoms in the clinical range. While spouses had higher scores than close relatives on symptom measures, significant differences were only established for anxiety symptoms (p<.02). A significant effect was found for gender, with women reporting more anxiety (p=.01) and depression (p=.02) symptoms than men. Results also showed a main effect for time, with anxiety (p<.0001), depression (p<.0001) and PTSD-related (p<.0001) symptoms being higher at admission than at discharge. Variables associated with the index patient, such as total body surface area burned, length of stay, number of ventilated days, facial burns, or level of care at admission, were not associated with outcome measures. CONCLUSIONS: Spouses and close relatives of burn survivors showed high levels of psychological distress in the first few days following admission, and more than a quarter still reported symptoms in the clinical range at discharge. Our analysis points to the need to offer psychological support and guidance to family members so that they can in turn provide effective support to the burn survivor.

Value of mechanical dyssynchrony as assessed by radionuclide ventriculography to predict the cardiac resynchronization therapy response.

AIMS: To assess the value of mechanical dyssynchrony measured by equilibrium radionuclide angiography (ERNA) in predicting long-term outcome in cardiac resynchronization therapy (CRT) patients. METHODS AND RESULTS: We reviewed 146 ERNA studies performed in heart failure patients between 2001 and 2011 at our institution. Long-term follow-up focused on death from any cause or heart transplantation. Phase images were computed using the first harmonic Fourier transform. Intra-ventricular dyssynchrony was calculated as the delay between the earliest and most delayed 20% of the left ventricular (LV) (IntraV-20/80) and inter-ventricular dyssynchrony as the difference between LV- and right ventricular (RV)-mode phase angles (InterV). Eighty-three patients (57%) were implanted with a CRT device after ERNA. Median follow-up was 35 [21-50] months. Twenty-four events were observed during the first 41 months. Median baseline ERNA dyssynchrony values were 28 [3 to 46] degrees for intraV-20/80 and 9 [-6 to 24] degrees for interV. Comparing survival between CRT and non-CRT patients according to dyssynchrony status, log-rank tests showed no difference in survival in patients with no ERNA dyssynchrony (P = 0.34) while a significant difference was observed in ERNA patients with high level of mechanical dyssynchrony (P = 0.004). CONCLUSION: ERNA mechanical dyssynchrony could be of value in CRT patient selection.