Clinical Experience with SonoVue in Myocardial Perfusion Imaging

Ultrasound-enhancing agents have the potential to evaluate myocardial perfusion, adding a new dimension to echocardiography. This article summarizes the clinical studies involving SonoVue, a new intravenous ultrasound contrast agent, in assessing myocardial perfusion. Safe and well tolerated, SonoVue coupled with echocardiography has the capability to identify perfusion abnormalities, as confirmed by scintigraphic imaging. While the optimal modalities for ultrasound perfusion assessment are not yet determined, numerous technical advances have been introduced: continuous infusion or slow intravenous administration of the agent, harmonic intermittent imaging, pulse inversion, background subtraction, color coding, and others. SonoVue is a promising new agent in the booming field of myocardial contrast echocardiography.     

Inter‐Breed Differences in Equine Forelimb Kinematics at the Walk

Linear, temporal and angular biokinematic characteristics of the forelimb at the walk in different breeds were determined, highlighting inter‐breed differences. Twenty‐three healthy stallions were used: ten Andalusians (AN), seven Arabs (AR) and six Anglo‐Arabs (AA). Height at the withers was significantly different between groups (P < 0.001). Six trials per horse were recorded using a levelled video camera (sampling frame rate 25 frames/s), digitized and analysed using a semi‐automatic movement analysis system. No statistically significant differences in speeds were recorded between breeds (P > 0.05). The only temporal parameter which was similar in the three breeds was the moment at which the hoof reached the highest point in its trajectory. The variables presenting the most significant differences were the percentages of deceleration and propulsion within the stance phase. ANOVA for angular variables showed that the greatest difference was in the range of angular movement of the carpal joint, being higher in AN, due to a lower minimum value. In the fetlock joint, the greatest difference was observed in minimum values, which differed in all three breeds. Significant inter‐breed differences were also observed for maximum limb retraction, being lowest in the AN group, followed by the AA and AR groups. This finding was reflected in the angular range of motion, despite smaller differences in the degree of limb protraction; very similar values were reported in all three breeds. As regards the elbow joint, no inter‐breed differences were observed in terms of minimum values, whereas differences were recorded for maximum and angular range of motion, higher values being displayed by the AR and AN groups than by AA animals. In conclusion, inter‐breed differences may be determined in equine forelimb biokinematics at the walk. This study distinguished between AN, AR and AA horses.     

Pharmacogenomic polygenic risk score for clopidogrel responsiveness among Caribbean Hispanics: A candidate gene approach

This multicenter clinical study was aimed at conducting a targeted pharmacogenomic association analysis of residual on‐clopidogrel platelet reactivity in 474 Caribbean Hispanic patients. Platelet reactivity was measured using the VerifyNow P2Y12 assay and clopidogrel resistance was defined as P2Y12 reaction units (PRUs) greater than or equal to 208. Genotyping was performed using the whole‐genome Infinium MEGA BeadChip array. An ancestry‐adjusted, weighted polygenic risk score (wPGxRS) was developed to account for the effect of multiple variants on PRU and compared between clopidogrel responders and nonresponders. The mean PRU across the study cohort was 173.8 ± 68.5 and 33.5% of patients were defined as clopidogrel resistant. Multivariate linear regression showed that 19% of PRU variability was attributed to nine independent predictors, with CYP2C19*2 (rs4244285) accounting for ~ 7% of observed PRU variation (p < 0.001). PON1 rs662, ABCB1/MDR1 rs2032582, PEAR1 rs12041331 carrier status, and the interaction between African ancestry and rs12041331 carriers also predicted PRU among the participants (p ≤ 0.05). A clear gene‐dose effect was detected between PRU and CYP2C19*2 genotype, consistent with previous studies in European patient populations, as well as rs12777823. Importantly, a significant positive correlation was detected between our novel wPGxRS (4 variants) and PRU among the Hispanic patient population (r _p = 0.35, p < 0.001). Moreover, the wPGxRS discriminated between nonresponders and responders (p = 0.003), indicating that this multigene‐based score is a useful predictor of clopidogrel resistance among Caribbean Hispanics. Taken together, these results help close the gap of knowledge on clopidogrel pharmacogenomics and its potential clinical implementation in this under‐represented population.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

CYP2C19*2 is significantly associated with an impaired response to clopidogrel in patients of mainly European ancestry, but this genetic variant accounts for only a small fraction of observed variability in clopidogrel resistance.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study answers the question of whether there is an association of relevant candidate pharmacogenes involved in clopidogrel absorption, metabolism, and pharmacodynamics with antiplatelet response among Caribbean Hispanics using a multigene‐based score approach.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study closes the existing gap of knowledge about clopidogrel pharmacogenomics in Caribbean Hispanics by both confirming and identifying relevant genetic determinants of clopidogrel responsiveness in this underrepresented population after developing an ancestry‐based polygenic risk score model.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

By gaining a better understanding of underlying determinants of poor clopidogrel response among marginally represented groups, such as Caribbean Hispanics, worldwide efforts to translate such findings into a global precision medicine paradigm of true benefit for everyone can finally bring cardiovascular health equity to the population at large.     

Dietary Patterns and Weight Status in Italian Preschoolers with Autism Spectrum Disorder and Typically Developing Children

Atypical eating habits are more common in children with autism spectrum disorders (ASD) than typically developing (TD) peers. Feeding problems may lead to the double burden of specific nutrient deficiencies and excessive weight gain, with a consequent increase in obesity prevalence. The dietary intake of Italian preschoolers with ASD compared to their TD peers and the impact of their dietary choices on their weight status and relationship to food selectivity (FS) were investigated. Dietary patterns and their associations with body mass index (BMI) were evaluated in 65 children with ASD and 82 peers with TD aged 1.3–6.4 years. Eating habits were assessed with a modified version of a parent-rated semi-quantitative Food Frequency Questionnaire. Moreover, the prevalence of FS and possible links with dietary patterns and BMI were investigated in the ASD group. Children with ASD consumed significantly higher amounts of simple sugars, processed and ultra-processed carbohydrates, both low- and high-fat animal proteins, and lower amounts of vegetables and fruits compared to peers with TD. The obesity rate was 1.5% in children with TD and more than fourfold (6.2%) in children with ASD, although the difference between groups was not statistically significant. FS was significantly more frequent in children with ASD than in peers with TD. Children with ASD and FS showed significantly lower annual intakes of vegetable proteins and fiber (considered essential nutrients for a healthy diet) than children with ASD without FS. Our results showed that children with ASD showed different dietary habits than those with TD, with the higher consumption of energy-dense foods and lower amounts of food-sourced fibers, which could place them at increased risk to develop overweight, obesity, and micronutrient deficiencies later in life.     

Enhancing obstetric and gynecology ultrasound images by adaptation of the speckle reducing anisotropic diffusion filter

OBJECTIVE: So far there is no ideal speckle reduction filtering technique that is capable of enhancing and reducing the level of noise in medical ultrasound (US) images, while efficiently responding to medical experts' validation criteria which quite often include a subjective component. This paper presents an interactive tool called evolutionary speckle reducing anisotropic diffusion filter (EVOSRAD) that performs adaptive speckle filtering on ultrasound B-mode still images. The medical expert runs the algorithm interactively, having a permanent control over the output, and guiding the filtering process towards obtaining enhanced images that agree to his/her subjective quality criteria. METHODS AND MATERIAL: We employ an interactive evolutionary algorithm (IGA) to adapt on-line the parameters of a speckle reducing anisotropic diffusion (SRAD) filter. For a given input US image, the algorithm evolves the parameters of the SRAD filter according to subjective criteria of the medical expert who runs the interactive algorithm. The method and its validation are applied to a test bed comprising both real and simulated obstetrics and gynecology (OB/GYN) ultrasound images. RESULTS: The potential of the method is analyzed in comparison to other speckle reduction filters: the original SRAD filter, the anisotropic diffusion, offset and median filters. Results obtained show the good potential of the method on several classes of OB/GYN ultrasound images, as well as on a synthetic image simulating a real fetal US image. Quality criteria for the evaluation and validation of the method include subjective scoring given by the medical expert who runs the interactive method, as well as objective global and local quality criteria. CONCLUSIONS: The method presented allows the medical expert to design its own filters according to the degree of medical expertise as well as to particular and often subjective assessment criteria. A filter is designed for a given class of ultrasound images and for a given medical expert who will later use the respective filter in clinical practice. The process of designing a filter is simple and employs an interactive visualization and scoring stage that does not require image processing knowledge. Results show that filters tailored using the presented method achieve better quality scores than other more generic speckle filtering techniques.