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Pyoderma gangrenosum (PG) is a neutrophilic dermatological disease, whose pathogenesis is still poorly clarified. Because of the lack of validated criteria for diagnosis and response, PG treatment is still challenging and should be differentiated in the inflammatory and non-inflammatory phases. Our study aimed to provide a new semi-quantitative approach for PG diagnosis and monitoring, identifying ultra-high-frequency ultrasound (UHFUS) early biomarkers associated with the transition between the two phases. We enrolled 13 patients affected by painful PG lesions evaluated during the inflammatory phase (T0) and during the non-inflammatory phase (T1): pain was measured by the Visual Analogue Scale (VAS); clinical features were recorded through digital photography; epidermis and dermis ultrasound (US) characteristics were evaluated by UHFUS examination with a 70 MHz probe (Vevo MD® FUJIFILM VisualSonics). In T1 UHFUS examination, the presence of hyperechoic oval structures was lower compared to T0 (p value < 0.05). An hyperechogenic structure within the oval structure, suggestive of a hair tract, was evident in T0 and absent in T1 (p value < 0.05). In T0, blood vessels appear as U-shaped and V-shaped anechoic structures with a predominance of U-shaped vessels (p value < 0.05) compared to the more regular distribution found in T1. Finding early biomarkers of the transition from the inflammatory to the non-inflammatory phase could provide new insight in terms of therapeutic decision making and response monitoring. The differences found by this study suggest a potential use of UHFUS for the development of an objective standardized staging method. Further investigations will be necessary to confirm our preliminary results, thus providing a turning point in PG early detection, differential diagnosis and treatment monitoring.

Background: To assess skin involvement in a cohort of patients with systemic sclerosis (SSc) by comparing results obtained from modified Rodnan skin score (mRSS), durometry and ultra-high frequency ultrasound (UHFUS). Methods: SSc patients were enrolled along with healthy controls (HC), assessing disease-specific characteristics. Five regions of interest were investigated in the non-dominant upper limb. Each patient underwent a rheumatological evaluation of the mRSS, dermatological measurement with a durometer, and radiological UHFUS assessment with a 70 MHz probe calculating the mean grayscale value (MGV). Results: Forty-seven SSc patients (87.2% female, mean age 56.4 years) and 15 HC comparable for age and sex were enrolled. Durometry showed a positive correlation with mRSS in most regions of interest (p = 0.025, ρ = 0.34 in mean). When performing UHFUS, SSc patients had a significantly thicker epidermal layer (p < 0.001) and lower epidermal MGV (p = 0.01) than HC in almost all the different regions of interest. Lower values of dermal MGV were found at the distal and intermediate phalanx (p < 0.01). No relationships were found between UHFUS results either with mRSS or durometry. Conclusions: UHFUS is an emergent tool for skin assessment in SSc, showing significant alterations concerning skin thickness and echogenicity when compared with HC. The lack of correlations between UHFUS and both mRSS and durometry suggests that these are not equivalent techniques but may represent complementary methods for a full non-invasive skin evaluation in SSc.

Background Ultrahigh-frequency ultrasound may represent a powerful tool for investigating the arterial properties of medium and small-size arteries. Aim of this study was: 1) to evaluate intra- and inter-operator reproducibility of radial artery vascular parameters (intima-media thickness –IMT- and diastolic diameter -DD), obtained both with a manual and an automatic approach; 2) to identify physiological correlates of radial IMT. Methods 40 healthy subjects were examined by Vevo MD (FUJIFILM, VisualSonics, Toronto, Canada); in 11 volunteers two B-mode clips (longitudinal view) of the radial artery were acquired for each subject by two skilled operators. IMT DD were measured manually and using an automatic software (Cardiovascular Suite, QUIPU, Pisa, Italy). Coefficient of variations (CV) and Bland-Altman analysis were employed. Results The manual approach provided intra-operator CV of 6.6% and 3.9% for DD and 6.5% and 6.6% for IMT (first and second operator). The automatic approach provided CV equal to 6.6%, 5.4%, 4.5% and 3%, respectively. Inter-operator CV were 11.3% for DD and 3.9% for IMT (manual), and 10.9% and 5.8% (automatic). Bland-Altman analysis provided non-significant bias for both IMT and DD measurements comparing manual and automatic approach. In the whole population, radial IMT was correlated with age (r = 0.35, p = 0.02) and pulse pressure (r = 0.41, p = 0.008), not with BMI (r = 0.05, p = 0.76)and mean blood pressure (r = 0.17, p = 0.28). No sex differences were observed. Conclusions We obtained good CV values for both the intra- and inter-operator reproducibility; furthermore, the manual and the automatic approach provided similar results. Radial IMT increases with age and pulse pressure.

Rationale and Aim This study is aimed at identifying possible patterns of vascular wall disarray and remodeling in radial arteries of patients with fibromuscular dysplasia (FMD), by means of ultrahigh frequency ultrasound (UHFUS). Methods UHFUS scans of the radial arteries and of 30 FMD patients and 30 healthy controls were obtained by VevoMD (70 MHz probe, FUJIFILM, VisualSonics, Toronto, Canada). 10 end-diastolic frames for each subject were analyzed. 74 radiomic features and 4 engineered parameters were extracted: intima-media thickness (IMT) and adventitia thickness (AT), an adjunctive acoustic interface for each layer (IMT and AT triple signal). The extracted parameters were used to train classification models, using Support Vector Machine Linear (SVM), K-Nearest Neighbors (KNN), Logistic Regression, Linear Discriminant Analysis (LDA). The models were then tested on an independent validation population (38 FMD patients and 28 healthy subjects). Results IMT (185 ± 46 vs 168 ± 37, p =) and AT (104 ± 34 vs 96 ± 35, p = 0.004) were significantly higher in FMD than in controls. IMT and AT triple signal were also more frequent in FMD than in control images ( p < for both). The most accurate classification models were LDA (sensitivity = 0.67, specificity = 0.76, accuracy = 0.71, AUC = 0.71) and Logistic Regression (sensitivity = 0.71, specificity = 0.72, accuracy = 0.71, AUC = 0.71). The models showed and accuracy of about 70% when tested on the validation population. Conclusions Wall ultrastructure of radial arteries of FMD patients is extensively altered: IMT and AT are thickened and the first and/or second layer of the arterial wall is splitted, showing a triple signal feature. Radiomic descriptors combined with engineered parameters allow to distinguish between radial images from FMD patients and controls with a 70% accuracy.

Rationale and Aim Essential hypertension is characterized by extensive alterations of arterial geometry and mechanical properties: increased stiffness, dilation and wall of large arteries, increased thickness in muscular arteries, small artery remodeling. This study is aimed at exploring function and structure of the digital arteries of the hand, muscular arteries with an internal diameter of 500–1000 mm, easily accessible by ultrahigh frequency ultrasound. Methods 24 hypertensive women (HT) and 37 healthy controls (C) were recruited. 5’-videoclips of left palmar digital arteries were obtained by VevoMD (FUJIFILM, VisualSonics, Toronto, Canada), by means of a 70 MHz probe (axial-lateral resolution 30–65 mm). An automatic system (Cvsuite, Quipu srl; Pisa, Italy) was used to measure intima-media thickness (IMT) and diameter. Distensibility and stiffness were then calculated using left brachial pulse pressure (PP - oscillometric) Results HT and C had similar age (57 ± 11 vs 53 ± 11 years, p = 0.22), BMI (24.9 ± 4.6 vs 24.5 ± 4.2 vs kg/m 2 , p = 0.80) and mean blood pressure (BP, 95 ± 12 vs 91 ± 12 mmHg, p = 0.24); HT showed slighlty higher PP (54 ± 14 vs 47 ± 10, p = 0.07). Palmar digital lumen tended to be higher in HT (804 ± 201 vs 696 ± 191 mm, p = 0.10), while IMT was similar (120 ± 23 vs 125 ± 36 mm, p = 0.81). Distensibility was reduced (21.4 ± 18.2 vs 29.0 ± 18.8 kPa 1 , p < 0.05), while stiffness was increased (7.95 ± 2.22 vs 6.72 ± 2.11 m/s, p < 0.005). Conclusions This is the first report of the presence of altered mechanical properties (i.e. increased stiffness) in muscular arteries with lumen <1000 mm of essential hypertensive women. These findings suggest that increased hemodynamic load characterizing hypertension lead to a different vascular phenotype in each arterial segment.

Background Spontaneous coronary dissection (SCAD) may represent a manifestation of fibromuscular dysplasia (FMD); thus, preclinical lesions might be found in extracoronary vessels with similar size and wall ultrastructure, such as the radial artery. Methods Two 5’-clips from the left radial artery were obtained by Vevo MD (70 MHz probe, FUJIFILM, VisualSonics). Radial wall showed two echogenic interfaces: the 1st (lumen-media) and the 2nd (media-adventitia). Intima-media (IMT), adventitia (AT), and global thickness (IMAT) and wall cross-sectional area (WCSA) Measured. Vascular wall disarray was assessed calculating the root mean square error (RMSE) between 20 gray-level profiles crossing the two interfaces and the profile obtained averaging them, normalized for the maximum value of the corresponding mean profile (RMSE/mean). Results 5 female SCAD patients and 9 healthy controls (C) were enrolled (age 45 ± 9 vs 45 ± 13years, p = 0.95; BMI 21 ± 3 vs 23 ± kg/mq, p = 0.22; mean BP 77 ± 5 vs 85 ± 10 mmHg, p = 0.053). 2nd interface peak was reduced in the SCAD group (97 ± 29 130 ± 19, p = 0.04), whereas RMSE/mean was increased (1.89 ± 0.68 vs 0.97 ± 0.30, p = 0.02). Similar values were found for the 1 st interface. IMT (0.165 ± 0.031 vs 0.125 ± 0.022mm, p = 0.03), but not AT (0.095 ± 0.020 vs 0.081 ± 0.020mm, p = 0.20) and IMAT (0.260 ± 0.049 vs 0.206 ± 0.030mm, p = 0.053), was significantly higher in SCAD. Radial internal diameter and wall/lumen ratio were similar: conversely WCSA was increased in SCAD (1.69 ± 0.48 vs 1.07 ± 0.37mm 2 , p = 0.02). Conclusions Radial arteries of SCAD patients were characterized by increased wall thickness. Furthermore, the 2 nd echogenic layer exhibited loss of echogenicity and inhomogeneity, features similar to FMD patients.

Aim This case-control study is aimed at identifying radial vascular wall abnormalities in patients with fibromuscular dysplasia (FMD). Methods High-frequency ultrasound scans of radial arteries were obtained by VevoMD (70 MHz probe, FUJIFILM, VisualSonics). Radial wall showed two echogenic interfaces: the 1 st (lumen-media) and the 2 nd (media-adventitia). Intima-media (IMT), adventitia (AT), and global thickness (IMAT) and wall cross-sectional area (WCSA) Measured. Vascular wall disarray was assessed calculating the root mean square error (RMSE) between 20 gray-level profiles crossing the two interfaces and the profile obtained averaging them, normalized for the maximum value of the corresponding mean profile (RMSE/mean). Results 11 treated hypertensive female FMD patients and 8 healthy controls (C) were enrolled (age 52 ± 5 vs 45 ± 13years, p = 0.51; BMI 26 ± 3 vs 23 ± 3kg/mg, p = 0.12; mean BP 97 ± 7 vs 85 ± 10 mmHg, p = 0.01). Radial lumen was similar; IMT (0.166 ± 0.037 vs 0.128 ± 0.022mm, p = 0.03), AT (0.114 ± 0.029 vs 0.083 ± 0.019mm, p = 0.008) and IMAT (0.281 ± 0.042 vs 0.211 ± 0.027mm, p = 0.003) were higher in FMD. Wall/lumen ratio was similar and WCSA increased in FMD. The maximum values of 1 st (121 ± 43 vs 157 ± 22, p = 0.09) and 2 nd interface 109 ± 44 vs133 ± 18, p = 0.09) tended to be lower, whereas RMSE/mean was higher in FMD (1 st 1.31 ± 0.24 vs 0.83 ± 0.32, p = 0.006; 2 nd 1.37 ± 0.38 vs 0.94 ± 0.32, p = 0.03). The difference was attenuated for the 1 st but not for the 2 nd interface when considering age and mean BP as covariates (p = 0.054 and p = 0.016 respectively). Conclusions The radial artery wall of hypertensive FMD patients shows increased thickness and its ultrastructure is characterized of loss of echogenicity and inhomogeneity of the two echogenic layers.

Prognosis in advanced gastric cancer (aGC) is predicted by clinical factors, such as stage, performance status, metastasis location, and the neutrophil-to-lymphocyte ratio. However, the role of body composition and sarcopenia in aGC survival remains debated. This study aimed to evaluate how abdominal visceral and subcutaneous fat volumes, psoas muscle volume, and the visceral-to-subcutaneous (VF/SF) volume ratio impact overall survival (OS) and progression-free survival (PFS) in aGC patients receiving first-line palliative chemotherapy. We retrospectively examined CT scans of 65 aGC patients, quantifying body composition parameters (BCPs) in 2D and 3D. Normalized 3D BCP volumes were determined, and the VF/SF ratio was computed. Survival outcomes were analyzed using the Cox Proportional Hazard model between the upper and lower halves of the distribution. Additionally, response to first-line chemotherapy was compared using the χ2 test. Patients with a higher VF/SF ratio (N = 33) exhibited significantly poorer OS (p = 0.02) and PFS (p < 0.005) and had a less favorable response to first-line chemotherapy (p = 0.033), with a lower Disease Control Rate (p = 0.016). Notably, absolute BCP measures and sarcopenia did not predict survival. In conclusion, radiologically assessed VF/SF volume ratio emerged as a robust and independent predictor of both survival and treatment response in aGC patients.

Background:In the last few decades many studies have investigated the role of major salivary glands ultrasound (SGUS) in the diagnostic work-up of patients with suspected primary Sjögren’s syndrome (pSS). Recent development of ultra-high-resolution ultrasound systems (UHFUS), with frequencies as high as 70 MHz and capability resolution as fine as 30 μm, has permit new diagnostic applications to a variety of superficial targets including labial salivary glands (LSGs). To date, however, no information are available regarding the use of UHFUS for the study of LSGs in humans.Objectives:To evaluate the feasibility and the diagnostic accuracy of UHFUS of LSGs in patients with suspected SS and to assess the correlations between LSG histopathology, UHFUS and SGUS.Methods:Consecutive patients with clinically suspected pSS were included in this study. All patients underwent a complete diagnostic work-up including conventional SGUS and LSG biopsy. The same expert pathologist calculated for all the samples the focus score (FS), number of foci and evaluated the presence of ectopic germinal centers (GCs). UHFUS of LSG was performed by specialized radiologists scanning first the central compartment of the inferior lip, and then both peripheral compartments. The following parameters were evaluated: distribution of the glands, parenchymal inhomogeneity (score 0-3, from normal to evident), fibrosis and eco color-Doppler vascular pattern and grade of vascular intensity.Results:We included 32 patients with suspected pSS. At the end of the work-up, pSS diagnosis was confirmed in 12/32 (37.5%) cases. No differences between pSS patients and no-SS sicca controls were observed in UHFUS findings related to LSG distribution and eco color-Doppler vascular parameters. By contrast, pSS patients presented statistically significant differences in peripheral UHFUS inhomogeneity (p=0.006), and a higher degree of fibrosis (p=0.01). Considering a score ≥2 in parenchymal inhomogeneity as suggestive for pSS, UHFUS appeared less specific than conventional SGUS (UHFUS Sp=70% vs SGUS Sp=95%) but more sensitive (UHFUS Se=83.3% vs SGUS Se = 58.3%). In addition, when we investigated the relationship between UHFUS, SGUS and LSG histopathology we found that the correlation coefficients between UHFUS inhomogeneity and LSG FS (UHFUS r=0.706** vs SGUS r=0.393*), number of foci (UHFUS r=0.712** vs SGUS r=0.445*), and number of ectopic GCs (UHFUS r=0.525** vs SGUS r=0.141), were significantly higher than those observed with conventional SGUS.Conclusion: the application of UHFUS to the study of LSG in pSS appeared feasible and sensitive. Because of the anatomical details obtained with this technique and its stronger correlation with LSG histopathology, UHFUS might offer unique advantages over the existing major salivary gland imaging modalities in pSS assessment.Disclosure of Interests:Chiara Baldini: None declared, Francesco Ferro: None declared, Veronica Iodice: None declared, Rossana Izzetti: None declared, Valentina Donati: None declared, Silvia Fonzetti: None declared, Teresa Oranges: None declared, Valentina Dini: None declared, Dania Cioni: None declared, Nicoletta Luciano: None declared, Rosa Maria Bruno: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Saverio Vitali: None declared, Davide Caramella: None declared