Novel anti-inflammatory therapies to reduce cardiovascular burden of psoriasis.

Psoriasis mainly affects the skin and joints and has serious impacts on the physical, emotional, and financial life of patients. Recent studies have demonstrated that other comorbidities are frequently detected in psoriatic patients. A strong association with the development of cardiovascular diseases, such as hypertension, myocardial infarction, and stroke is responsible for the shortened (by 4.5-5 years) life expectancy of severe psoriatic patients. Systemic inflammation plays an important role in the interrelationship between psoriasis and atherosclerotic plaque formation, which is a common immunopathogenic pathway that explains the multiorgan involvement in psoriasis. As far life-threatening cardiovascular diseases are very often symptom-free, the treating dermatologist's responsibility is to initiate interdisciplinary holistic patient care, which may lead to directly saved patients' lives. Holistic care of severe psoriatic patients should include regular cardiac monitoring using cardiovascular imaging modalities and functional testing to detect even subclinical coronary artery disease. Effective anti-inflammatory treatment with biologic therapies may have beneficial effects on the cardiovascular state and may reduce the incidence of cardiac events. The authors review the latest findings on the shared immunopathogenic background of psoriasis and cardiovascular diseases and discuss the available data about the cardiovascular responses to the currently used biologic treatments.

Impact of effective tumor necrosis factor-alfa inhibitor treatment on arterial intima-media thickness in psoriasis: results of a pilot study.

BACKGROUND: Psoriasis is associated with higher incidence of atherosclerotic comorbidities. Sustained arterial wall inflammation mediated by common cytokines of psoriasis and atherogenesis precedes atherosclerotic plaque development. Increased intima-media thickness (IMT) is an accepted indicator of subclinical atherosclerosis and has been reported in severe psoriasis. OBJECTIVE: This pilot study aimed to clarify whether effective long-term tumor necrosis factor-alfa inhibition decreases IMT in psoriasis. METHODS: In 16 patients with severe psoriasis, the Psoriasis Area and Severity Index score was calculated before therapy (etanercept, infliximab, adalimumab) and after 6-month treatment. Simultaneously, carotid and brachial IMT was measured by high-resolution, B-mode ultrasonography. Difference between initial and 6-month IMT values was determined for monitored arteries collectively and separately in carotid and brachial arteries. RESULTS: All of 16 patients achieved Psoriasis Area and Severity Index 75, and 14 of 16 achieved Psoriasis Area and Severity Index 90 improvement. In the group of patients without initial calcified atherosclerotic plaques (13 of 16) significant IMT decrease was detected when arteries were measured collectively (P = .0002). Initial and follow-up data differed significantly also at individual analysis of carotid (P = .011) and brachial (P = .006) arteries. Eleven of 13 patients had initial carotid IMT exceeding age-adjusted normal values. The other group (3 of 16) with initial manifest plaques showed increasing IMT tendency. Their baseline ultrasonography revealed carotid IMT above the upper limit of healthy adults' age-adjusted values. LIMITATIONS: Study limitation involves small patient numbers, self-controlled study design, and lack of patients' stratification according to common cardiovascular risk factors. CONCLUSION: In our pilot study effective tumor necrosis factor-alfa inhibition was found to decrease IMT in psoriatic patients without irreversible atherosclerotic plaques. Further analysis is recommended to confirm and complete our primary observations.

Preliminary Clinical Experience with a Novel Optical-Ultrasound Imaging Device on Various Skin Lesions.

A compact handheld skin ultrasound imaging device has been developed that uses co-registered optical and ultrasound imaging to provide diagnostic information about the full skin depth. The aim of the current work is to present the preliminary clinical results of this device. Using additional photographic, dermoscopic and ultrasonic images as reference, the images from the device were assessed in terms of the detectability of the main skin layer boundaries and characteristic image features. Combined optical-ultrasonic recordings of various types of skin lesions (melanoma, basal cell carcinoma, seborrheic keratosis, dermatofibroma, naevus, dermatitis and psoriasis) were taken with the device (N = 53) and compared with images captured with a reference portable skin ultrasound imager. The investigator and two additional independent experts performed the evaluation. The detectability of skin structures was over 90% for the epidermis, the dermis and the lesions. The morphological and echogenicity information observed for the different skin lesions were found consistent with those of the reference ultrasound device and relevant ultrasound images in the literature. The presented device was able to obtain simultaneous in-vivo optical and ultrasound images of various skin lesions. This has the potential for further investigations, including the preoperative planning of skin cancer treatment.

Automated Skin Lesion Classification on Ultrasound Images.

The growing incidence of skin cancer makes computer-aided diagnosis tools for this group of diseases increasingly important. The use of ultrasound has the potential to complement information from optical dermoscopy. The current work presents a fully automatic classification framework utilizing fully-automated (FA) segmentation and compares it with classification using two semi-automated (SA) segmentation methods. Ultrasound recordings were taken from a total of 310 lesions (70 melanoma, 130 basal cell carcinoma and 110 benign nevi). A support vector machine (SVM) model was trained on 62 features, with ten-fold cross-validation. Six classification tasks were considered, namely all the possible permutations of one class versus one or two remaining classes. The receiver operating characteristic (ROC) area under the curve (AUC) as well as the accuracy (ACC) were measured. The best classification was obtained for the classification of nevi from cancerous lesions (melanoma, basal cell carcinoma), with AUCs of over 90% and ACCs of over 85% obtained with all segmentation methods. Previous works have either not implemented FA ultrasound-based skin cancer classification (making diagnosis more lengthy and operator-dependent), or are unclear in their classification results. Furthermore, the current work is the first to assess the effect of implementing FA instead of SA classification, with FA classification never degrading performance (in terms of AUC or ACC) by more than 5%.

Automated seeding for ultrasound skin lesion segmentation.

The segmentation of cancer-suspicious skin lesions using ultrasound may help their differential diagnosis and treatment planning. Active contour models (ACM) require an initial seed, which when manually chosen may cause variations in segmentation accuracy. Fully-automated skin segmentation typically employs layer-by-layer segmentation using a combination of methods; however, such segmentation has not yet been applied on cancerous lesions. In the current work, fully automated segmentation is achieved in two steps: an automated seeding (AS) step using a layer-by-layer method followed by a growing step using an ACM. The method was tested on images of nevi, melanomas, and basal cell carcinomas from two ultrasound imaging systems (N=60), with all lesions being successfully located. For the seeding step, manual seeding (MS) was used as a reference. AS approached the accuracy of MS when the latter used an optimal bounding rectangle based on the ground truth (Sørensen-Dice coefficient (SDC) of 72.3 vs 74.6, respectively). The effect of varying the manual seed was also investigated; a 0.7 decrease in seed height and width caused a mean SDC of 54.6. The results show the robustness of automated seeding for skin lesion segmentation.

Impact of Interleukin-17 Inhibitor Therapy on Arterial Intima-media Thickness among Severe Psoriatic Patients.

BACKGROUND: Psoriasis is frequently accompanied by cardiovascular diseases based on the shared immunopathogenic pathway. Authors determined the effect of interleukin (IL)-17 inhibitor therapy on arterial intima-media thickness (IMT) among severe psoriatic patients. METHODS: Thirty-one severe psoriatic patients were enrolled. Twenty received secukinumab and 11 received ixekizumab. Before treatment initiation and after 6 months, the carotid-brachial-femoral IMT, the Psoriasis Area Severity Index (PASI), the Dermatology Life Quality of Index (DLQI) and the EuroQol Visual Analogue Scale (EQ VAS) were evaluated. RESULTS: After 6 months, significant ameliorations were observed in PASI (p < 0.001) from 18 to 0, in DLQI (p < 0.001) from 17 to 0, in EQ VAS (p < 0.001) from 60 to 90, in right carotid IMT (p < 0.001) from 1.1 mm to 0.8 mm, in left carotid IMT (p < 0.001) from 1.1 mm to 0.7 mm, in right brachial IMT (p < 0.001) from 0.75 mm to 0.6 mm, in left brachial IMT (p < 0.001) from 0.8 mm to 0.5 mm, in right femoral IMT (p < 0.001) from 0.9 mm to 0.7 mm and in left femoral IMT (p < 0.001) from 0.8 mm to 0.7 mm. CONCLUSIONS: By reducing the inflammation of the vascular wall, anti-IL-17 therapy may have a beneficial long-term effect on cardiovascular complications of systemic inflammation.

A real-time data-based scan conversion method for single element ultrasound transducers.

The current work investigates the performance of a real-time scan conversion algorithm for generating a 2-D ultrasound image from a laterally scanned single-element ultrasound transducer, which has applications in point-of-care devices such as for skin imaging. The algorithm employs a fixed calibration curve to update a predefined image grid in real time. Simulations showed that the calibration curve (with a maximum of 1) is robust to changes in scatterer concentration (8.3×10-3 mean absolute error), signal to noise ratio (1.0×10-3 mean absolute error for -5 dB SNR), and can be accurately predicted from a small number (31) of point scatterers (6.9×10-3 mean absolute error). Good agreement was also found between the calibration curves obtained from simulated and experimental data (1.19×10-2 mean absolute error). The scan conversion algorithm was validated by evaluation of the position estimation errors on both simulations and experiments. Clinical images of skin lesions (N = 20) demonstrate the feasibility of the algorithm for real, non-homogeneous tissue. Use of a fixed calibration curve compared to an adaptive calibration curve gave similar accuracies in the scanning step size range of 150-350 µm (with an average overlap of the accuracy ranges of 92.94% for simulations and 42.83% for experiments), and a 350-fold improvement in computation time.

Histology-based simulations of ultrasound imaging: methodology.

Simulations of ultrasound (US) images based on histology may shed light on the process by which microscopic tissue features translate to a US image and may enable predictions of feature detectability as a function of US system parameters. This technical note describes how whole-slide hematoxylin and eosin-stained histology images can be used to generate maps of fractional change in bulk modulus, whose convolution with the impulse response of the US system yields simulated US images. The method is illustrated by two canine mastocytoma histology images, one with and the other without signs of intra-operative hemorrhaging. Quantitative comparisons of the envelope statistics with corresponding clinical US images provide preliminary validation of the method.