Background and aims: Deep-vein thrombosis (DVT) is a widely diffused condition, and its accurate staging has major clinical and therapeutic implications. Ultrasound elastography (UE) is a rapidly evolving imaging technique that allows quantification of elastic tissue properties and could play a crucial role in determining thrombus age. The aim of this review is to find clinical evidence regarding the application of UE in the evaluation of DVT and its usefulness in differentiating thrombosis age. Methods: A literature search of clinical studies was performed to identify the ability of UE of discriminate acute, subacute, and chronic DVT. Heterogeneity and publication bias were calculated. In accordance with the study protocol, a qualitative analysis of the evidence was planned. The results were summarized with a comprehensive summary table of study characteristics and baseline characteristics of participant patients. Results: Nine studies matched the predetermined eligibility requirements for this systematic review regarding the risk of bias; the greatest criticalities were found within the domains of patient selection and index test. Based on the quality assessment, two publications were excluded from the qualitative synthesis because of the presence of significant applicability concerns. Among the seven studies that were considered eligible for qualitative synthesis, four evaluated strain elastography and three evaluated shear-wave elastography. Despite significant differences concerning study design, thrombus age definitions, and patient characteristics, nearly all studies demonstrated an increase in thrombus stiffness according to DVT age. Conclusions: UE could play a key role in routine ultrasound examination of DVT. The measurement of thrombus stiffness has a high biological plausibility and its use is supported by the finding of a correlation between the stiffness and the progression of the DVT age.

Summary: Chronic venous disease (CVD) is a prevalent condition leading to significant morbidity and affecting quality of life. Among conservative treatment strategies, venoactive drugs are often recommended by major guidelines for the management of CVD. Bromelain and vitamin C are now emerging as promising options in the management of several chronic diseases owing to their anti-inflammatory, immunoregulatory, and antioxidant properties, though evidence remains scarce in this setting. This systematic review of the literature, endorsed by the Italian Society of Angiology and Vascular Medicine ( Societa Italiana di Angiologia e Patologia Vascolare, SIAPAV), aims to evaluate the efficacy and safety of these compounds in the treatment of CVD. A comprehensive search yielded nine studies, two on bromelain and seven on vitamin C. No studies have evaluated the effects of bromelain and vitamin C alone or in combination, whereas both molecules were administered in combination with other nutritional supplements. Overall, CVD-related symptoms and edema seem to improve with dietary supplement containing these two compounds, with no major safety issues reported. Bromelain and vitamin C may thus represent attractive options in the management of patients with symptomatic CVD and/or presence of venous edema, provided optimal conservative treatment is in place. Dedicated clinical studies are needed to clarify the efficacy and safety of a combination of these molecules in CVD management.

Background: Chronic venous disease (CVD) is a prevalent condition associated with significant morbidity and impaired quality of life. Venoactive nutraceuticals are widely used as part of conservative management and are cited in major guidelines, yet recommendations remain heterogeneous and clinical practice varies substantially. This study aimed to establish expert consensus on the clinical use of these agents in CVD within the Italian vascular community. Methods: A three-round modified Delphi was conducted among 21 Italian vascular specialists (May–July 2025). Consensus was defined as ≥70% agreement. Statements addressed CEAP classification, symptom assessment, use and perceived effectiveness of individual agents, combination regimens, and topical formulations. Results: Consensus supported routine use of CEAP and its 2020 revision, the clinical distinction between CVD (C0–C2) and chronic venous insufficiency (CVI) (C3–C6), and systematic classification of patients as symptomatic or asymptomatic. Strong agreement endorsed the use of selected venoactive nutraceuticals across all CEAP classes and supported combination therapy as more effective than monotherapy. An oral fixed-dose combination of diosmin, ruscus, melilotus, Vitis vinifera, and horse chestnut extract, pre-selected as a test case to evaluate the plausibility of combining agents with complementary mechanisms, was considered a reasonable first-line conservative option. Topical preparations were endorsed across C1–C6, particularly for CVI and to reduce heaviness, reflecting their perceived value as safe adjuncts despite the limited availability of high-quality evidence. No consensus was reached for ruscus, horse chestnut, hydroxyethylrutosides, red vine leaf extract, anthocyanosides, or β-arbutin in monotherapy. The panel agreed on the need to update clinical guidelines to reflect emerging evidence on venoactive nutraceuticals. Conclusions: This Delphi provides structured expert consensus on the use of venoactive nutraceuticals in CVD. Combination therapy integrating multiple physiological effects is considered more effective than single agents. Further research is required to validate combination regimens and topical formulations and to determine their impact on patient-reported outcomes.

Dynamic contrast-enhanced ultrasound (D-CEUS) could be a valuable tool for the non-invasive diagnosis of hepatocellular carcinoma (HCC) with atypical vascular imaging features. Between January 2021 and November 2023, consecutive patients with chronic liver disease and liver nodules who were candidates for liver biopsy were enrolled in this cohort study. CEUS was performed in all patients before biopsy and categorized according to the CEUS Liver Imaging Reporting and Data System (LI-RADS). Clips were examined using VueBox® software. Clinical and ultrasound parameters were compared among the different histological entities, analyzed with univariable analysis, and incorporated into a logistic regression model for HCC diagnosis. The diagnostic accuracy of the identified model was evaluated by receiver operating characteristic (ROC) curve and relative AUC. The model was then tested on a validation cohort comprising consecutive patients from two centers. A total of 88 patients (57 with HCC, 17 with intrahepatic cholangiocarcinoma, 11 with liver metastases, and three with benign lesions) were enrolled. Statistically significant differences between patients with and without HCC in the training cohort were incorporated in an optimal logistic regression model that included the following predictive variables: sex, number of nodules ≥4, peripheral rim-like hyperenhancement, and peak enhancement (PE) ratio (PE-rim-like enhancement-Sex-Nodules≥4; PERSoN4). The model displayed high accuracy (AUC 0.91) for the diagnosis of HCC. In the validation cohort, the model showed a sensitivity of 48.8% and a specificity of 100.0%, with a positive predictive value (PPV) of 100.0%, maintaining good diagnostic accuracy (AUC of 0.74). PERSoN4 could improve the performance of CEUS LI-RADS criteria, possibly leading to a non-invasive diagnosis of HCC in nearly 50% of patients currently referred for liver biopsy. However, this model requires further external validation before entering clinical practice. Accurate non-invasive diagnosis of HCC remains challenging in patients with atypical vascular patterns on CEUS, providing the scientific rationale for developing a multiparametric D-CEUS-based risk model that integrates quantitative perfusion analysis with clinical and imaging features. Our findings suggest that the PERSoN4 model could meaningfully enhance the diagnostic performance of CEUS LI-RADS, particularly by identifying a subset of patients in whom HCC can be diagnosed with very high specificity and PPV, which is relevant for hepatologists, radiologists, and multidisciplinary tumor boards managing indeterminate nodules. This approach could reduce the need for liver biopsy in nearly half of currently eligible patients, streamlining diagnostic pathways and potentially lowering procedure-related risks and costs. However, given the moderate sensitivity and the limited sample size, further large-scale external validation is essential before widespread clinical implementation.