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Supplementary Table S1. Characteristics of surgical HCC patients analysed in this study. Supplementary Table S2. Patients assessed for circulating miR-221. Supplementary Table S3. Primer sequences and PCR conditions for the cloning experiment. Supplementary Table S4. Primer sequences and PCR conditions. Supplementary Table S5. Antibodies used in Western blot analysis.

Figure S2. Histopathological images of HCC nodules arisen in DEN-treated rats following Sorafenib administration. Nodules that responded to Sorafenib displayed large necrotic areas.

Purpose: The aberrant expression of miR-221 is a hallmark of human cancers, including hepatocellular carcinoma (HCC), and its involvement in drug resistance, together with a proved in vivo efficacy of anti-miR-221 molecules, strengthen its role as an attractive target candidate in the oncologic field. The discovery of biomarkers predicting the response to treatments represents a clinical challenge in the personalized treatment era. This study aimed to investigate the possible role of miR-221 as a circulating biomarker in HCC patients undergoing sorafenib treatment as well as to evaluate its contribution to sorafenib resistance in advanced HCC.Experimental Design: A chemically induced HCC rat model and a xenograft mouse model, together with HCC-derived cell lines were employed to analyze miR-221 modulation by Sorafenib treatment. Data from the functional analysis were validated in tissue samples from surgically resected HCCs. The variation of circulating miR-221 levels in relation to Sorafenib treatment were assayed in the animal models and in two independent cohorts of patients with advanced HCC.Results: MiR-221 over-expression was associated with Sorafenib resistance in two HCC animal models and caspase-3 was identified as its target gene, driving miR-221 anti-apoptotic activity following Sorafenib administration. Lower pre-treatment miR-221 serum levels were found in patients subsequently experiencing response to Sorafenib and an increase of circulating miR-221 at the two months assessment was observed in responder patients.Conclusions: MiR-221 might represent a candidate biomarker of likelihood of response to Sorafenib in HCC patients to be tested in future studies. Caspase-3 modulation by miR-221 participates to Sorafenib resistance. Clin Cancer Res; 23(14); 3953–65. ©2017 AACR.

Background: Contrast-enhanced ultrasonography (CEUS) is used to evaluate vascularity of the gastrointestinal wall in neoplastic and inflammatory diseases. Objective: To assess the feasibility of CEUS for the evaluation of duodenal perfusion in dogs with inflammatory bowel disease (IBD). Animals: Forty-two dogs with IBD and 20 clinically healthy dogs. Methods: All CEUS studies of the duodenum were analyzed to obtain time-intensity curves and perfusion parameters. The procedure was repeated in 12 IBD dogs 2months after a standardized treatment. Results: On CEUS, the duodenal wall showed a typical perfusion pattern characterized by a radial and simultaneous enhancement of the wall in all dogs. On qualitative assessment, no differences were observed in contrast medium distribution between healthy and affected dogs, or between dogs with IBD before and after treatment. Peak intensity (PI) and area under the curve (AUC) significantly differed between healthy (PI=3.58 arbitrary units [au; 1.86-4.93 au] and AUC=47.63 au seconds [aus, 22.68-62.15]) and affected dogs (PI=5.10au [0.63-15.16 au] and AUC=63.62 aus [5.31-212.20 aus]; P=.03 and.03, respectively). No significant differences were found for the perfusion parameters before and after treatment. Conclusions and Clinical Importance: We showed that CEUS allows discrimination between IBD affected dogs and healthy dogs by evaluation of time-intensity curves, but did not provide useful information for monitoring therapeutic response. The qualitative assessment identified no significant differences between healthy and affected dogs, or between dogs before and after treatment.

Background Atrial fibrillation (AF) is a common supraventricular arrhythmia more frequently observed in large breed dogs. Objectives Estimate the prevalence of AF in dogs with myxomatous mitral valve disease (MMVD) and identify risk factors for developing AF. Animals A total of 2194 client-owned dogs with MMVD, including 1280, 588, 290, and 36 dogs in ACVIM stages B1, B2, C, and D, respectively. Methods Retrospective, cross-sectional study. The medical databases of 3 veterinary teaching hospitals were reviewed. Inclusion criteria were a diagnosis of MMVD after complete cardiovascular evaluation and cardiac rhythm assessment using routine 2-minute ECG or good quality ECG tracing during echocardiographic examination. Results Atrial fibrillation was diagnosed in 59 dogs with a prevalence of 2.7%. Univariate analysis showed that mixed breed, male sex, advanced ACVIM stage, left atrial and ventricular enlargement, fractional shortening (FS), and presence of pulmonary hypertension were significantly associated with development of AF. According to 2 multivariable models, the left atrium (LA)-to-aorta ratio (odds ratio [OR] = 14.011, 7.463-26.304), early trans-mitral velocity (OR = 2.204, 1.192-4.076), body weight (OR = 1.094, 1.058-1.130), and FS (OR = 0.899, 0.865-0.934) and LA (OR = 5.28, 3.377-8.092), advanced ACVIM stage (OR = 4.922, 1.481-16.353), and FS (OR = 0.919, 0.881-0.959) were significant predictors of AF for models 1 and 2, respectively. Conclusions and clinical importance Atrial fibrillation is an uncommon complication of MMVD and is significantly associated with the more advanced stage of the disease, increased LA dimension and body weight, and decreased FS.

Objectives The aims of this study were to describe the radiographic features of cardiogenic pulmonary oedema (CPE) in a large group of cats with left-sided cardiac disease, and to determine the association between the radiographic features of CPE and the underlying cardiac disease. Methods Thoracic radiographs of cats with CPE and echocardiographic evidence of left-sided cardiac disease and left atrial enlargement (LAE) were reviewed, and cardiac silhouette, pulmonary vessels and pulmonary parenchyma evaluation were performed. Interstitial and/or alveolar patterns were classified according to their distribution (ie, diffuse, multifocal or focal) and location (ie, craniodorsal, cranioventral, caudodorsal, caudoventral and perihilar). A Student’s t-test and Mann–Whitney U-test, or the two-proportion z-test, were used to compare continuous or categorical variables, respectively, between cats affected by the two most represented cardiac diseases, namely hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM). Results Seventy-one cats were included; among them, 46 (64.7%) and 13 (18.3%) had presented for HCM and RCM, respectively. Subjective and objective cardiomegaly, and subjective and objective LAE were detected in 97.2% and 91.9% of cats and in 80.3% and 40.6% of cats, respectively. Pulmonary artery abnormalities, in particular caudal pulmonary artery dilation, were found in 77.5% of cats. Pulmonary artery to pulmonary vein ratio = 1 was found in 71.8% and 55% cats on right lateral and ventrodorsal or dorsoventral views, respectively. Interstitial (57.8%) and mixed interstitial–alveolar (38%) pattern, multifocal (84.5%) and symmetrical (75%) distribution with prevalent ventrocaudal (65.6% of cats) and ventrocranial (60.9% of cats) locations were most frequently observed. No difference was found for any of these radiographic features between cats with HCM and RCM. Conclusions and relevance Moderate-to-severe cardiomegaly and LAE, caudal pulmonary artery and vein dilation, as well as a ventral, multifocal and symmetrical interstitial pulmonary pattern, were the main radiographic features of CPE in evaluated cats. Underlying cardiac disease did not influence the aforementioned radiographic features.

Cardiac disease in guinea pigs has been reported in the literature; however, reference intervals for normal radiographic heart size obtained using objective measurement methods have not been provided for this species. The aim of this prospective, reference interval study was to describe cardiac dimensions in presumed healthy guinea pigs using the vertebral heart scale (VHS) from thoracic radiographs, as described for dogs and cats. Furthermore, an anatomical study was carried out to compare the radiographic and anatomical findings. Thoracic radiographs were acquired in right lateral recumbency for 30, client-owned, conscious, presumed healthy guinea pigs and radiographs were acquired in left lateral recumbency for 10 presumed healthy guinea pigs as comparisons. The influence of sex, age, body weight (BW), and recumbency on the VHS and absolute cardiac measurements was investigated. The median (interquartile range; IQR) VHS was 7.4 (7.1-7.6). No differences emerged between the VHS measured in right versus left lateral recumbency (P=.41) or between sexes (P=.16). The VHS values were not influenced by age (P=.53) or BW (P=.26). The anatomical study was carried out on 10 guinea pig cadavers, and in situ and ex situ cardiac measurements were taken using a caliper. A median (IQR) 7.5 (7.2-8.0) VHS was assessed by this anatomical study. The reference intervals provided should be useful tools in the future for the radiographic interpretation of cardiac size in guinea pigs in clinical practice.

Background Improvement in cardiac function has been demonstrated after thyroxine treatment in humans with hypothyroidism using the myocardial performance index (MPI). Cardiac changes after thyroxine supplementation are poorly documented in dogs with spontaneous hypothyroidism and comparison with clinically healthy dogs is lacking. Objectives To evaluate the electrical activity and mechanical function of the heart in dogs with primary hypothyroidism at baseline (T0) and after thyroxine supplementation (T60). Animals Forty client‐owned dogs with hypothyroidism and 20 clinically healthy dogs. Methods Prospective cohort study. Selected electrocardiographic and echocardiographic variables, including the MPI, were measured in all dogs at T0 and in 30 hypothyroid dogs at T60. Results Hypothyroid dogs had significantly decreased median or mean heart rate (HR), P wave amplitude, and R wave amplitude (P = .04, P = .002, and P = .003, respectively) and E‐point‐to‐septal separation normalized to body weight (EPSSn) and trans‐mitral E wave velocity (E max; P

Congenital heart diseases have rarely been described in rabbits. The purpose of the present case report is to describe the clinical, radiographic, echocardiographic, and pathological features of a partial atrioventricular septal defect in a pet rabbit. A 3-month-old, 380-g male vaccinated pet rabbit was presented for decreased activity, increased respiratory rate and effort, anorexia, and decreased fecal output of 2 days duration. Total body radiographic images revealed severe cardiomegaly associated with enlarged caudal pulmonary vessels and increased interstitial to alveolar lung pattern. Echocardiographic imaging showed evidence of distended heart chambers, abnormal flow through the atria, and mitral valve regurgitation. The rabbit was treated with furosemide and an angiotensin-converting enzyme inhibitor but rapidly deteriorated and died. Necropsy confirmed the dilation of both ventricles and the presence of a partial atrioventricular septal defect associated with an ostium primum atrial septal defect just over the tricuspid valve and the mitral valve.

Objectives The aim of this study was to describe the results of two-dimensional (2D) and contrast-enhancement ultrasound (CEUS) in four cats with intestinal ischaemia. Methods Data were collected from hospital records of all cats that had intestinal ischaemia between January 2012 and August 2018. The inclusion criteria were complete abdominal ultrasound examination, colour flow Doppler and CEUS of lesions, confirmation of intestinal ischaemia detected by visual assessment of avascular intestinal segment at surgery, and/or necropsy and histopathology. All images and video clips were reviewed by the same experienced operator. Results Four cats with different intestinal ischaemic lesions were included in the study: duodenal perforating ulcer, jejunal necrotising enteritis, necrosis secondary to jejunojejunal intussusception and iatrogenic damage of jejunal arteries. On the 2D ultrasound, all intestinal lesions were characterised by non-specific findings: focal hypoechoic wall thickening with loss of normal layering associated with hyperechoic mesentery surrounding the intestinal tract. CEUS showed a reduced or absent enhancement of the intestinal lesions in comparison to the surrounding perfused wall. Conclusions and relevance Intestinal ischaemia is a potentially fatal disorder. Grey-scale, colour and power Doppler ultrasonography are not sensitive for evaluating this condition. Our preliminary findings illustrate the usefulness of CEUS for the detection of intestinal wall impaired perfusion in cats.

With the growing interest in cardiac magnetic resonance imaging (cMRI), veterinary radiologists will increasingly be asked to use this modality to answer complex cardiological questions. Plane alignment is crucial for reproducible assessment of the heart. Anesthesia time is a limiting factor in cMRI. Aims of this prospective experimental study were to introduce a flow chart for standardized cMRI-examination in dogs, to test it for reproducibility using a cardiac CT simulation and to estimate time requirements needed to complete the examination accurately. Six operators (3 radiologists, 1 cardiologist, 1 imaging-resident, 1 technician) simulated a cMRI examination on CT-scans of 6 healthy Beagle dogs twice within two to four weeks. Assessment included qualitative and quantitative scoring of plane quality and time requirements. The quality of planes was high for the left and moderate for the right side of the heart. The intraclass correlation coefficient (ICC) of linear measurements of structures on the left was good to excellent (ICC-range: 0.789-0.948) but dropped to moderate to poor levels for the right side (ICC-range: 0.429-0.738). The median time required to complete a full examination was 30 (range: 13-103) min in the first and 24 (range: 15-62) min in the second evaluation. It differed significantly between operators and was consistently shorter for the left than for the right side. In conclusion, a new standardized scheme for cMRI can be quickly adopted by radiologists with some expertise in cross sectional imaging. Qualitative and quantitative results were highly reproducible for the left but less for the right side.

Background Atrial fibrillation (AF) occurs in dogs with myxomatous mitral valve disease (MMVD) as a consequence of left atrial (LA) dilatation, and it affects survival and quality of life. Objectives To evaluate the usefulness of echocardiography in predicting the first occurrence of AF in dogs with MMVD. Animals Forty-four client-owned dogs with MMVD, 22 dogs that developed AF, and 22 dogs that maintained sinus rhythm. Methods Retrospective observational study. Medical databases were reviewed for dogs that developed AF during the year after diagnosis of MMVD (AF group). The last echocardiographic examination obtained while still in sinus rhythm was used to derive selected variables. For each dog with AF, a control dog matched for body weight, class of heart failure, and LA dimension was selected. Echocardiographic results including LA volumes and LA speckle tracking echocardiography (STE)-derived variables were measured. Results Among the tested echocardiographic variables, only LA diameter (P = .03) and left ventricular internal diameter in diastole (P = .03) differed significantly between groups, whereas body weight-indexed variables of cardiac dimension as well as LA volumes and volume-derived functional variables were not different. Among the STE-derived variables, peak atrial longitudinal strain (PALS) results differed significantly between the AF group (23.8% ± 8.6%) and the control group (30.5% ± 9.6%; P = .03). A value of PALS ≤28% predicted AF occurrence with sensitivity and specificity of 0.80 and 0.65, respectively. Conclusions and clinical importance Absolute cardiac diameters and LA STE (in particular, PALS) are useful echocardiographic predictors for the development of AF in dogs with MMVD.

Background: The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. Objectives: To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). Animals: One-hundred and fifteen dogs of different breeds with MMVD. Methods: Prospective cohort study. Conventional morphologic and echo-Doppler variables, LA areas and volumes, and STE-based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac-related death. Results: Most of the tested variables, including all LA STE-derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76-11.24; P

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Tumors of adrenal and thyroid glands have been associated with vascular invasions&mdash, so-called tumor thrombi, both in humans and dogs. The detection and characterization of venous thrombi is an important diagnostic step in patients with primary tumors for both surgical planning and prognosis. The aim of this study was to describe the use of contrast-enhanced ultrasonography (CEUS) for the characterization of tumor thrombi. Dogs with tumor thrombus who underwent bi-dimensional ultrasound (B-mode US) and CEUS were included. Seven dogs were enrolled in this retrospective case series. On B-mode US, all thrombi were visualized, and vascular distension and thrombus-tumor continuity were seen in three and two cases, respectively. On color Doppler examination, all thrombi were identified, seemed non-occlusive and only two presented vascularity. On CEUS, arterial-phase enhancement and washout in the venous phase were observed in all cases. Non-enhancing areas were identified in the tumor thrombi most likely representing non-vascularized tissue that could potentially be embolized in the lungs after fragmentation of the tumor thrombi. On the basis of these preliminary study, CEUS appeared to be useful for the characterization of malignant intravascular invasion.

Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.

Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.

There are no reports on use of contrast-enhanced ultrasonography (CEUS) in equine obstetrics. The aim of this study was to evaluate feasibility and safety of CEUS as a technique for monitoring and quantifying perfusion of the uterus throughout normal pregnancy in mares. Two pregnant Standardbred healthy mares underwent real-time two-dimensional ultrasonography, Doppler ultrasound, and CEUS of the uteroplacental unit on day 40, at 90–100 days, then every 30 days, and every 10 days during the last month of pregnancy. Foeto-placental well-being and in particular fetal heart rate as an index of fetal stress were monitored, and main uterine arteries diameter and Doppler parameter resistance index (RI) were measured. Contrast-enhanced ultrasonography quantitative perfusion variables, peak intensity, arrival time, time to peak from injection, and time to peak from initial rise were measured. No contrast medium was observed in the fetus, umbilical vein, and allantochorionic layer of the uteroplacental unit. Neonatal foals were clinically normal. Placenta was normal at postpartum gross examination in both mares. A progressive bilateral increase in diameter of the uterine arteries was noticed for both mares. The Doppler RI reduced early during the first half of the pregnancy and then remained relatively unchanged until delivery. Contrast enhancement was satisfactory in all CEUS. Peak intensity showed overall fivefold and 10-fold increase throughout pregnancy in mare no. 1 and no. 2, respectively. No discrete trend of change was noticed for other CEUS variables. Contrast-enhanced ultrasonography is feasible and seems safe to study microperfusion of the uterus during normal pregnancy in mares.

Purpose: The aberrant expression of miR-221 is a hallmark of human cancers, including hepatocellular carcinoma (HCC), and its involvement in drug resistance, together with a proved in vivo efficacy of anti-miR-221 molecules, strengthen its role as an attractive target candidate in the oncologic field. The discovery of biomarkers predicting the response to treatments represents a clinical challenge in the personalized treatment era. This study aimed to investigate the possible role of miR-221 as a circulating biomarker in HCC patients undergoing sorafenib treatment as well as to evaluate its contribution to sorafenib resistance in advanced HCC. Experimental Design: A chemically induced HCC rat model and a xenograft mouse model, together with HCC-derived cell lines were employed to analyze miR-221 modulation by Sorafenib treatment. Data from the functional analysis were validated in tissue samples from surgically resected HCCs. The variation of circulating miR-221 levels in relation to Sorafenib treatment were assayed in the animal models and in two independent cohorts of patients with advanced HCC. Results: MiR-221 over-expression was associated with Sorafenib resistance in two HCC animal models and caspase-3 was identified as its target gene, driving miR-221 anti-apoptotic activity following Sorafenib administration. Lower pre-treatment miR-221 serum levels were found in patients subsequently experiencing response to Sorafenib and an increase of circulating miR-221 at the two months assessment was observed in responder patients. Conclusions: MiR-221 might represent a candidate biomarker of likelihood of response to Sorafenib in HCC patients to be tested in future studies. Caspase-3 modulation by miR-221 participates to Sorafenib resistance. Clin Cancer Res; 23(14); 3953–65. ©2017 AACR.

PURPOSE: The aim of this study was to assess the early response to sorafenib using ultrasound molecular imaging in a murine model of hepatocellular carcinoma (HCC). PROCEDURES: A xenograft model of HCC was established. Then, mice were divided in two groups and received treatment (sorafenib) or placebo for 14 days. The treatment group was further divided into non-responders and responders according to the degree of growth. Contrast enhanced ultrasound (CEUS) was performed using VEGFR-2 targeted microbubbles (BR55, Bracco Suisse SA, Geneva, Switzerland). Dedicated software was used to quantify the amount of bound microbubbles in the tumor as a numerical value (differential targeted enhancement (dTE)). Tumors were then excised and western blot analysis performed. RESULTS: The dTE values decreased from day 0 to day +14 both in the treatment and control groups, but were lower in the former. The non-responder group had higher dTE levels at day 2 compared to responders (p = 0.019). CONCLUSION: BR55 appears to be useful in the prediction of response to sorafenib in a xenograft model of HCC.

OBJECTIVE To determine variability of global longitudinal strain (GLS) and strain rate (SR) measurements in dogs with and without cardiac disease derived from 2-D speckle tracking echocardiography (STE) by use of various software. ANIMALS 2 cohorts comprising 44 dogs (23 cardiovascularly healthy and 21 with cardiac disease) and 40 dogs (18 cardiovascularly healthy and 22 with cardiac disease). PROCEDURES Transthoracic echocardiographic images in each cohort were analyzed with vendor-independent software and vendor-specific 2-D STE software for each of 2 vendors. Values for GLS and SR obtained from the same left parasternal apical views with various software were compared. Intraobserver and interobserver variability was determined, and agreement among results for the various software was assessed. RESULTS Strain analysis was not feasible with vendor-independent software for 20% of images obtained with the ultrasonography system of vendor 1. Intraobserver and interobserver coefficient of variation was < 10% for GLS values, whereas SR measurements had higher variance. There was a significant difference in GLS and SR obtained for each cohort with different software. Evaluation of Bland-Altman plots revealed wide limits of agreement, with variance for GLS of up to 6.3 units in a single dog. CONCLUSIONS AND CLINICAL RELEVANCE Results of longitudinal strain analysis were not uniform among software, and GLS was the most reproducible measurement. Significant variability in results among software warrants caution when referring to reference ranges or comparing serial measurements in the same patient because changes of < 6.5% in GLS might be within measurement error for different postprocessing software.

A 9-year-old Giant Schnauzer was referred for polyuria and polydipsia. On abdominal ultrasound, a hyperechoic mass with low color Doppler signal was detected in the medial right hepatic lobe. Contrast-enhanced ultrasound (CEUS) demonstrated increased enhancement of the mass during the arterial phase, and contrast washout during portal and late phases with decreased enhancement relative to the liver. These findings were consistent with primary liver malignancy or liver metastasis. A final diagnosis of cholangiocellular adenoma was made based on histopathology. To our knowledge, this is the first description of a benign hepatic neoplasm exhibiting malignant CEUS characteristics in a dog.

OBJECTIVE To determine the sensitivity, specificity, and interobserver variability of survey thoracic radiography (STR) for the detection of heart base masses (HBMs) in dogs. DESIGN Retrospective case-control study. ANIMALS 30 dogs with an HBM and 120 breed-matched control dogs (60 healthy dogs and 60 dogs with heart disease and no HBM). PROCEDURES In a blinded manner, 2 observers (designated as A and B) evaluated STR views from each dog for a mass-like opacity cranial to the heart, tracheal deviation, cardiomegaly, findings suggestive of pericardial effusion or right-sided congestive heart failure, and soft tissue opacities suggestive of pulmonary metastases. Investigators subsequently provided a final interpretation of each dog's HBM status (definitely affected, equivocal, or definitely not affected). RESULTS Considering equivocal interpretation as negative or positive for an HBM, the sensitivity of STR for diagnosis of an HBM was 40.0% (95% confidence interval [CI], 22.5% to 57.5%) and 56.7% (95% CI, 38.9% to 74.4%), respectively, for observer A and 63% (95% CI, 46.1% to 80.6%) and 80.0% (95% CI, 65.7% to 94.3%), respectively, for observer B. The corresponding specificity was 96.7% (95% CI, 93.5% to 99.9%) and 92.5% (95% CI, 87.8% to 97.2%), respectively, for observer A and 99.2% (95% CI, 97.5% to 100%) and 92.5% (95% CI, 87.8% to 97.2%), respectively, for observer B. The presence of a mass-like opacity cranial to the heart or tracheal deviation, or both, was significantly associated with a true diagnosis of HBM. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that STR is a highly specific but not a highly sensitive predictor of HBM in dogs.

Objectives This study aimed to assess non-invasively the cardiovascular effects of high-dose medetomidine on healthy male cats undergoing semen collection. Methods Haemodynamic evaluations were assessed on the basis of clinical examination, systolic arterial pressure (SAP) and transthoracic echocardiographic examination. Eight client owned, male domestic shorthair cats were sedated with a bolus of medetomidine intramuscularly (IM; 0.13 mg/kg), and semen collection was performed. A second transthoracic echocardiographic examination and SAP measurement were carried out 15 mins after sedation. At the end of the examination, the patients received a bolus of atipamezole (0.3 mg/kg) IM. Results The cats were deeply sedated, relaxed and laterally recumbent during the entire procedure. No rhythm abnormalities were observed during the examinations and no significant increase in SAP was recorded. Heart rate dropped from 200 ± 33 to 92 ± 13.1 beats per min after sedation. There was a significant increase in left ventricular dimensions and the left atrial area. The parameters of left ventricular systolic function were reduced, as were systemic and pulmonary cardiac outputs. Peak diastolic wave velocities were significantly reduced, while isovolumic contraction and relaxation time of the left ventricle were prolonged. Aortic valve insufficiency was recorded for all cats, while mitral valve insufficiency was noted in five cats. None of the subjects developed systolic anterior motion of the mitral valve. Conclusions and relevance The protocol allowed us to collect good semen samples in healthy cats. However, high-dose medetomidine induces significant haemodynamic effects on the feline heart, mainly due to a reduced heart rate, an increased cardiac preload and impaired systolic function. The animals recovered from the anaesthesia, after antagonist administration, without showing any clinically relevant consequences.

Electrocardiographic tracings of an English Bulldog referred for cardiogenic shock due to an orthodromic atrioventricular reciprocating tachycardia conducted with intraventricular conduction disturbance and mimicking ventricular tachycardia (VT) are presented. At admission the surface ECG showed a wide QRS complex tachycardia (WCT) that was converted to sinus rhythm using manual cardioversion (chest thump). This change revealed pre-existing right bundle branch block, and a final diagnosis of supraventricular tachycardia (SVT) with intraventricular conduction disturbance was made. Electrophysiologic study defined the SVT mechanism as an atrioventricular macroreentrant tachycardia mediated by a single mid-septal accessory pathway. The differentiation between various types of WCT is essential when antiarrhythmic therapy is considered. The surface ECG should be systematically evaluated in order to recognize the characteristic features of SVT and VT. Moreover chest thump procedure can be very helpful in the attempt to convert the rhythm to sinus rhythm and to correctly recognize the underlying arrhythmia. © 2012 Elsevier Ltd. All rights reserved.

An 11-year-old, male, Pekinese was examined because of a sporadic, nonresponsive, nonproductive cough. Radiographically there was cardiomegaly and a soft tissue mass in the cranial mediastinum. Echocardiographically, chronic degenerative valvular disease was diagnosed. Furthermore, a large anechoic structure located cranial to the right atrium was detected. Computed tomography was performed to define the mediastinal mass and a right auricle aneurysm was diagnosed. The dog died suddenly 1 day after the diagnostic imaging procedures. At necropsy, a right auricular aneurysm without discontinuity of the pericardial sac was confirmed. Intrapericardial right auricular aneurysm should be included in the differential diagnoses of cranial mediastinal masses.

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A retrospective search was conducted to evaluate the diagnostic accuracy of the vertebral heart score (VHS) and other related radiographic indices in the detection of cardiac enlargement associated with different cardiac disorders in the cat. One hundred and five cats with a complete echocardiographic examination and radiographic examination of the thorax with at least two orthogonal views were enrolled. Eighty-three cats had different cardiac disorders, 72 with left-sided cardiac disorders (LSCD) and 11 with right-sided cardiac disorders; 22 cats were free of cardiovascular abnormalities. Measurements of VHS and cardiac long and short axes on lateral (L) and dorsoventral or ventrodorsal radiographs were obtained. Receiver operating characteristic curves were calculated to evaluate the diagnostic accuracy of each radiographic index in differentiating between cats with cardiac disorders or cats with LSCD and cats without cardiac abnormalities and, among cats with LSCD, between those with no or mild left atrial enlargement (LAE) or those with moderate-to-severe LAE and healthy cats. The L-VHS at the cut-off of 7.9 had high diagnostic accuracy in distinguishing cats with LSCD and moderate-to-severe LAE from healthy cats, but all the other radiographic indices were moderately accurate in distinguishing between cats with overall cardiac disorders or LSCD, either with no or mild LAE and moderate-to-severe LAE, and healthy cats. The considered radiographic indices were also moderately accurate in predicting different degrees of LAE in cats with LSCD. Radiographic indices are reasonably specific, but less sensitive predictors of cardiac enlargement in cats with heart disorders.

Objective—To evaluate the diagnostic accuracy of radiographically derived measurements of vertebral heart score (VHS) and sphericity index (SI) in the detection of pericardial effusion (PE) in dogs. Design—Retrospective case-control study. Animals—51 dogs with PE associated with various cardiac disorders, 50 dogs with left- or right-sided cardiac disorders without PE, 50 dogs with bilateral cardiac disorders without PE, and 50 healthy dogs. Procedures—Measurements of VHS on lateral (lateral VHS) and ventrodorsal (ventrodorsal VHS) radiographs, SI on lateral (lateral SI) and ventrodorsal (ventrodorsal SI) radiographs, and global SI (mean of lateral SI and ventrodorsal SI) were obtained. Receiver operating characteristic curves were calculated to evaluate the diagnostic accuracy of the radiographic indexes at differentiating dogs with PE from those with other cardiac disorders without PE. Results—Measurements of lateral and ventrodorsal VHS were significantly higher in dogs with PE, compared with values for all dogs without PE. Measurements of lateral, ventrodorsal, and global SI were significantly lower in dogs with PE, compared with values for all dogs without PE. Cutoff values of > 11.9, > 12.3, and ≤ 1.17 for lateral VHS, ventrodorsal VHS, and global SI, respectively, were the most accurate radiographic indexes for identifying dogs with PE. Conclusions and Clinical Relevance—Cardiac silhouettes of dogs with PE were larger and more rounded, compared with those of dogs with other cardiac disorders without PE. Objective radiographic indexes of cardiac size and roundness were only moderately accurate at distinguishing dogs with PE from dogs with other cardiac disorders without PE.

Objective—To noninvasively assess the influence of ingestion of a standard meal on gallbladder volume (GBV) in healthy cats. Animals—10 healthy adult domestic shorthair cats (4 neutered females, 5 neutered males, and 1 sexually intact male). Procedures—Nonsedated cats were positioned in dorsal and left lateral recumbency to obtain ultrasonographic measurements of the gallbladder via the subcostal and right intercostal acoustic windows, respectively. Gallbladder volume was calculated from linear measurements by use of an ellipsoid formula (volume [mL] = length [mm] × height [mm] × width [mm] × 0.52). Measurements were recorded after food was withheld for 12 hours (0 minutes) and at 5, 15, 30, 45, 60, and 120 minutes after cats were fed 50 g of a standard commercial diet (protein, 44.3%; fat, 30.3%; and carbohydrate, 15.6% [dry matter percentage]). Results—Agreement between gallbladder linear measurements or GBV obtained from the subcostal and right intercostal windows was good. Feeding resulted in linear decreases in gallbladder linear measurements and GBV. Via the subcostal and intercostal windows, mean ± SD GBV was 2.47 ± 1.16 mL and 2.36 ± 0.96 mL, respectively, at 0 minutes and 0.88 ± 0.13 mL and 0.94 ± 0.25 mL, respectively, at 120 minutes. Gallbladder width most closely reflected postprandial modification of GBV. Conclusions and Clinical Relevance—Results indicated that ultrasonographic assessment (via the subcostal or right intercostal acoustic window) of postprandial changes in GBV can be used to evaluate gallbladder contractility in cats. These data may help identify cats with abnormal gallbladder emptying.