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16 pages, 2899 KB  
Article
A New Pearl in Chronic Venous Disease Pathophysiology—The Duplex Ultrasound and the Elastographic Features of Lymph Nodes Varicose Veins in the Groin
by Ioana-Teofana Dulgheriu, Carolina Solomon, Stefan Timofte, Anca-Ileana Ciurea and Sorin Marian Dudea
Diagnostics 2026, 16(6), 905; https://doi.org/10.3390/diagnostics16060905 - 18 Mar 2026
Viewed by 367
Abstract
Background/Objectives: Chronic venous disease (CVD) is a prevalent condition marked by valve dysfunction and increased pressure in lower limb veins. The trans-nodal veins in the inguinal region and Scarpa triangle, which connect the superficial and deep venous systems, provide new insight into [...] Read more.
Background/Objectives: Chronic venous disease (CVD) is a prevalent condition marked by valve dysfunction and increased pressure in lower limb veins. The trans-nodal veins in the inguinal region and Scarpa triangle, which connect the superficial and deep venous systems, provide new insight into venous insufficiency pathways. While they function normally in healthy individuals, they can become dilated in chronic venous disease or following surgery. The purpose of this study was to provide an ultrasonographic anatomical description of intranodal varicose veins and to assess possible changes in the stiffness of varicose, dilated inguinal lymph nodes. Methods: The study comprised 92 participants, including 69 women and 23 men, who underwent Doppler ultrasound examinations of the lower-limb venous system, focusing on the groin from both a descriptive morphological and an elastographic perspective. The diagnosis of lymph node varices was made according to established criteria, its severity was assessed using an original classification system, and shear-wave elastography (SWE) values were recorded. Results: More than 83% of patients with operated CVD had lymph node varicose veins. Patients with lymph node varicose veins had larger groin lymph node diameters than patients with CVD without lymph node varicose pathology. The mean shear wave elastography values were significantly lower in the group with lymph node varices compared to the group without (12.2 ± 1.1 kPa vs. 20.1 ± 2.3 kPa; p < 0.05). Elastographic values correlate with lymph node diameter (p = 0.039) and with varicose vein grade (p < 0.001). Conclusions: Intranodal varices may indicate disease progression. These vascular abnormalities impact SWE measurements by altering tissue mechanics. It is imperative to consider the interactions between the lymphatic and venous systems in the management of CVD to improve patient outcomes. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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12 pages, 1821 KB  
Article
Effectiveness and Limitations of Endovenous Laser Ablation for Anterior Saphenous Vein Insufficiency: A Single-Center Retrospective Study
by Eva Gruber, Merian Ranjbaryan, Bachar el Jamal, Syrus Karsai, Eike Sebastian Debus and Lars Müller
J. Clin. Med. 2026, 15(5), 1733; https://doi.org/10.3390/jcm15051733 - 25 Feb 2026
Viewed by 476
Abstract
Background: Anterior saphenous vein (ASV) incompetence represents the third most common form of truncal varicose veins, and evidence for endovenous laser ablation (EVLA) in this setting remains limited. Methods: We evaluated outcomes of EVLA in cases with dominant ASV insufficiency. All [...] Read more.
Background: Anterior saphenous vein (ASV) incompetence represents the third most common form of truncal varicose veins, and evidence for endovenous laser ablation (EVLA) in this setting remains limited. Methods: We evaluated outcomes of EVLA in cases with dominant ASV insufficiency. All EVLA procedures performed by a single surgeon between April 2019 and December 2023 for primary ASV reflux (ASV-R) were compared with a cohort containing all EVLA treatments for great saphenous vein (GSV) insufficiency without ASV reflux from April to December 2019 (GSV-R). We used a 1470-nm diode laser with radially emitting fibers for the interventions. Results: We included 378 patients (mean age 49.5 years): 208 and 256 treated limbs in the ASV-R and GSV-R cohorts, respectively. Female patients were more frequent in the ASV-R cohort than in the GSV-R cohort (80.5% vs. 62.9%, p < 0.001). ASV-R cases exhibited concomitant GSV insufficiency in 54.3% of cases. Redo procedures due to initial treatment failure were more frequent in ASV-R (1.9% vs. 0%, p = 0.04). Over a mean follow-up period of 332 days, 16 recurrences occurred in the ASV-R cohort compared with 4 in the GSV-R cohort, corresponding to a significantly increased hazard of recurrence in ASV-R (HR 8.41, 95% CI 2.78–25.4). Rates of subsequent foam sclerotherapy (16.8% vs. 10.5%) and minor complications (5.3% vs. 4.3%) did not differ significantly between ASV-R and GSV-R, respectively. ASV-R cases without concomitant GSV reflux demonstrated a higher need for secondary sclerotherapy, compared to ASV-R cases with additional GSV insufficiency. Conclusions: Our findings suggest that EVLA for ASV insufficiency is technically more challenging and yields inferior outcomes than EVLA for GSV incompetence. These considerations should be taken into account during preoperative planning and patient counseling. Further prospective and comparative analyses are needed to better define the effectiveness of thermal ablation strategies in ASV insufficiency and to support patient-centered, individualized treatment decisions. Full article
(This article belongs to the Section Vascular Medicine)
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7 pages, 169 KB  
Case Report
Vulvar Varicosities and Pelvic Venous Disorders in Nongravid Women: A Case Series
by Benjamin Daniel, Jennifer Dennison and John Regan
J. Clin. Med. 2026, 15(4), 1558; https://doi.org/10.3390/jcm15041558 - 16 Feb 2026
Viewed by 449
Abstract
Background/Objectives: The authors hypothesize that some vulvar varicosities are due to and can be treated by addressing underlying pelvic venous disorders (PeVDs). The purpose of this single center retrospective study is to evaluate vulvar varicosity resolution following treatment of an underlying PeVD. [...] Read more.
Background/Objectives: The authors hypothesize that some vulvar varicosities are due to and can be treated by addressing underlying pelvic venous disorders (PeVDs). The purpose of this single center retrospective study is to evaluate vulvar varicosity resolution following treatment of an underlying PeVD. Methods: This study is a single center, retrospective case series from 2010 to 2025 of all patients evaluated in a single vein clinic with vulvar varicosities confirmed by examination and/or imaging, most commonly CT abdomen and pelvis with contrast. Inclusion criteria were presence of vulvar varicosities, evidence of an underlying PeVD, treatment with either left ovarian vein embolization or left iliac stenting, and at least one month of follow-up. PeVD was defined as a combination of suggestive imaging findings (left ovarian vein dilation or left common iliac compression) combined with associated symptoms including pelvic pain and pelvic fullness. Exclusion criteria included prior intervention for PeVDs, other vascular pathologies such as vascular malformations, incomplete documentation, and inaccessible imaging. Results: A total of 18 women with an average of 44 years of age met inclusion and exclusion criteria for the study. Thirteen patients (72.2%) presented with lower extremity varicosities at the same visit. Fifteen patients were multiparous at the time of presentation with a para status averaging 2.5. Ten patients (55.6%) had left ovarian reflux confirmed venographically and received ovarian vein embolization. Preoperative or intraoperative left ovarian venous diameter averaged 7.8 mm. Seven patients (38.9%) had left common iliac vein compression and received self-expandable left common iliac venous stenting. Preoperative CT suggested compression and all patients had intraoperative intravascular ultrasound (IVUS) prior to stenting with an average stenosis of 75.9%. One patient had both pathologies and received both treatments. No patients underwent right ovarian vein embolization nor had venographic evidence of right ovarian reflux. A total of 16 out of 18 patients (88.9%) had complete resolution of PeVDs. One patient had partial response for pelvic pain at one month of follow-up. Another patient had recurrence of pelvic pain symptoms and is being worked up for Nutcracker syndrome. All patients had resolution of their vulvar varicosities on follow-up examination. Conclusions: Vulvar varicosities may be indicative of an underlying PeVD. Vulvar varicosity resolution is associated with PeVD treatment in this case series. Therefore, vulvar varicosities are an important physical exam finding in pelvic examination and referral to a vein specialist should be considered. Additional higher powered, prospective, and randomized studies are indicated to further evaluate this relationship. Full article
(This article belongs to the Special Issue Management of Female Pelvic Floor Disorders and Incontinence)
19 pages, 2492 KB  
Article
Chemical Profiling and Vascular Effects of a Hydroalcoholic Extract of Calophyllum longifolium Willd: Role of Nitric Oxide and Potassium Channels
by Diego Aravena, Javier Palacios, Cristián A. Véliz-Quezada, Gabriela V. Aguirre-Martínez, Julio Benites, David J. Greensmith, Adrián Paredes, Fredi Cifuentes, Mario J. Simirgiotis, Frank R. León-Vargas, Daniel Asunción-Alvarez, Iván M. Quispe-Díaz and Roberto O. Ybañez-Julca
Plants 2026, 15(4), 594; https://doi.org/10.3390/plants15040594 - 13 Feb 2026
Viewed by 583
Abstract
Calophyllum spp. infusions are used to treat varicose veins, hemorrhoids, and hypertension. However, the chemical composition and mechanisms of action are poorly understood. Accordingly, the aim of this study was to investigate the phytochemical composition and vascular effects of hydroalcoholic extracts of Calophyllum [...] Read more.
Calophyllum spp. infusions are used to treat varicose veins, hemorrhoids, and hypertension. However, the chemical composition and mechanisms of action are poorly understood. Accordingly, the aim of this study was to investigate the phytochemical composition and vascular effects of hydroalcoholic extracts of Calophyllum longifolium. Phytochemical profiling was performed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-ESI-Q-TOF-MS). Extract effects on rat aortic rings and aortic vascular smooth muscle cells (VSMCs) were evaluated using wire myography and photometric measurement of intracellular Ca2+, respectively. UHPLC-ESI-Q-TOF-MS revealed the presence of coumarins, xanthones, flavonoids, triterpenes, and phenolic acids. Coumarin–resveratrol hybrids, such as gut-70 derivatives, were also abundant. In aortic rings from normotensive rats, C. longifolium induced a biphasic vascular response whereby low concentrations (1 μg/mL) produced significant vascular relaxation, whereas high concentrations (100 μg/mL) produced contraction. Blockade of ATP-sensitive (KATP) or voltage-gated (KV) potassium channels attenuated these effects. Furthermore, effects were not observed in preparations preincubated with L-NG-Nitro-L-arginine methyl ester (L-NAME) or in endothelium-denuded rings. In aortic VSMCs, extracts (1 µg/mL) rapidly reduced sarcoplasmic reticulum (SR) Ca2+ content. This study provides the first UHPLC-ESI-Q-TOF-MS chemical profile of C. longifolium, revealing diverse bioactive metabolites. It is also the first to demonstrate that C. longifolium exerts an endothelium-dependent, nitric oxide- and Ca2+-mediated biphasic effect on vascular function. Taken together, these findings highlight C. longifolium as a potential novel source of vasculotropic phytopharmaceuticals. Full article
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21 pages, 1034 KB  
Review
Superficial Venous Thrombosis in Non-Varicose Veins: A Narrative Review
by Marco Mangiafico, Francesco Lorenzo Di Pino and Luca Costanzo
J. Clin. Med. 2026, 15(3), 1082; https://doi.org/10.3390/jcm15031082 - 29 Jan 2026
Viewed by 624
Abstract
Background: Superficial venous thrombosis (SVT) is an inflammatory and thrombotic disorder affecting superficial veins. While varicose veins (VVs) are the primary risk factor, SVT occurring in non-varicose veins (NVVs) is a critical clinical finding, often acting as a sentinel marker for severe systemic [...] Read more.
Background: Superficial venous thrombosis (SVT) is an inflammatory and thrombotic disorder affecting superficial veins. While varicose veins (VVs) are the primary risk factor, SVT occurring in non-varicose veins (NVVs) is a critical clinical finding, often acting as a sentinel marker for severe systemic pathologies. Aims: This review aims at examining incidence, mechanisms, underlying causes, and clinical outcomes of SVT within the NVV population. Materials and Methods: We conducted a comprehensive narrative review of the existing medical literature. Results: SVT in NVVs is frequently associated with systemic conditions, including inherited or acquired thrombophilia, visceral or hematologic malignancies (notably Trousseau’s syndrome), vasculitis (e.g., Behçet’s syndrome), and connective tissue disorders. Specific manifestations like migratory SVT or Mondor’s disease provide crucial diagnostic clues. Notably, NVV-SVT carries a significantly higher risk of recurrence and venous thromboembolic events compared to VV-associated cases. Conclusions: A thorough diagnostic work-up is essential for patients with NVV-SVT to ensure early detection of underlying systemic diseases. Although current management does not differentiate between VV and NVV cases, the increased thromboembolic risk in the latter suggests a need for tailored therapeutic approaches. Further prospective studies are required to evaluate differentiated anticoagulant strategies regarding dosage and duration for this high-risk population. Full article
(This article belongs to the Section Vascular Medicine)
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20 pages, 2641 KB  
Article
Multilayer Perceptron Artificial Neural Network to Support Nurses’ Decision-Making on Topical Therapies for Venous Ulcers: Construction, Validation, and Evaluation
by Simone Karine da Costa Mesquita, Luana Souza Freitas, Isabelle Pereira da Silva, Anna Alice Carmo Gonçalves, Alcides Viana de Lima Neto, Carlos Alberto de Albuquerque Silva, Nielsen Castelo Damasceno Dantas, Rhayssa de Oliveira e Araújo and Isabelle Katherinne Fernandes Costa
BioMedInformatics 2025, 5(4), 72; https://doi.org/10.3390/biomedinformatics5040072 - 17 Dec 2025
Viewed by 752
Abstract
Background: Due to the complexity of venous ulcer treatment, the role of nurses is critical, and artificial intelligence, particularly artificial neural networks of the Multilayer Perceptron type, can be effective tools that support professionals with objective, real-time evaluation. Thus, the present study aims [...] Read more.
Background: Due to the complexity of venous ulcer treatment, the role of nurses is critical, and artificial intelligence, particularly artificial neural networks of the Multilayer Perceptron type, can be effective tools that support professionals with objective, real-time evaluation. Thus, the present study aims to develop a network to assist in nurse decision-making regarding topical therapies for the treatment of venous ulcers. Methods: A methodological study with a technological focus and quantitative approach was conducted. The Unified Process methodology model was used, based on the Rational Unified Process strategy, following four phases: conception, elaboration, construction, and transition. Results: The development of the artificial neural network involved the collaboration of three specialists who evaluated clinical cases and images of venous ulcers to identify the topical therapies used in their clinical practice. A total of 23 dressings were selected, studied, and grouped into evaluation protocols to create the neural network flowchart, which defined the structure of the network. This network was then used by 13 nurses through the VenoTEC app (version 1.2, developed by the authors, Natal, Brazil). Conclusions: The software developed showed promising results in the initial evaluations conducted. The network achieved the highest accuracy in the initial tests and received a very good usability rating from the nurses who participated in the evaluation. The small dataset limits the generalization capability of the findings. Further studies are needed with additional datasets and populations. Full article
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8 pages, 9223 KB  
Case Report
Natural or Violent Death? Deceptive Crime Scene in a Case of Ruptured Varicose Vein
by Gennaro Baldino, Pietro Tarzia, Gabriele Rotter, Simona Calabrese, Marija Čaplinskienė and Elvira Ventura Spagnolo
Forensic Sci. 2025, 5(4), 70; https://doi.org/10.3390/forensicsci5040070 - 1 Dec 2025
Viewed by 1330
Abstract
Background: Fatal hemorrhage from ruptured varicose veins is a rare event that may mimic violent death given the quantity and distribution of blood at the scene. Accurate determination of cause and manner of death requires careful scene investigation, autopsy, histology, and ancillary [...] Read more.
Background: Fatal hemorrhage from ruptured varicose veins is a rare event that may mimic violent death given the quantity and distribution of blood at the scene. Accurate determination of cause and manner of death requires careful scene investigation, autopsy, histology, and ancillary methods such as bloodstain pattern analysis (BPA). Case presentation: We describe an 80-year-old woman found deceased at home, with evidence of extensive bloodstaining, no significant external trauma except a small laceration over a varicosity, and ultimately a ruptured branch of the small saphenous vein. The cause of death was hemorrhagic shock due to spontaneous varicose vein rupture. Discussion: This case reinforces the importance of integrating death scene findings (including shoe prints, bloodstain distribution), anatomical dissection, histology, and toxicology to exclude non-natural causes. We also review recent similar cases in the literature, noting risk factors, presentation, and common pitfalls. Conclusions: Forensic investigations of massive bleeding in elderly, isolated individuals should include varicose vein rupture in the differential. A multidisciplinary approach is essential to avoid misclassification of manner of death. Full article
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19 pages, 353 KB  
Article
Prevalence of Varicose Veins Among Teaching Professionals and Their Impact on Quality of Life and Job Performance: A Cross-Sectional Study
by Safaa M. Elkholi, Danah Alotaibi, Reem Alrashdi, Reema Bin Subeh, Hajer Aljudeie, Rema Aljabr, Eman M. Mortada and Reem M. Alwhaibi
Healthcare 2025, 13(23), 3041; https://doi.org/10.3390/healthcare13233041 - 25 Nov 2025
Cited by 1 | Viewed by 1539
Abstract
Background: Varicose veins (VVs) are a chronic venous condition that can negatively affect mobility, psychosocial health, and occupational function, especially in professions involving prolonged standing or sitting. Teaching professionals are particularly at risk due to static postural demands and limited workplace ergonomic [...] Read more.
Background: Varicose veins (VVs) are a chronic venous condition that can negatively affect mobility, psychosocial health, and occupational function, especially in professions involving prolonged standing or sitting. Teaching professionals are particularly at risk due to static postural demands and limited workplace ergonomic support. Objective: This study aimed to estimate the prevalence of VVs among teaching professionals in Saudi Arabia and assess their impact on quality of life (QoL) and job performance. Methods: A cross-sectional study was conducted employing a stratified convenience sampling strategy among 400 school and university educators across different regions of Saudi Arabia. Data collection took place over four months, from mid-January to end-April 2025. Data were collected through a validated self-administered online questionnaire comprising demographic information and three standardized tools: The Arabic version of the Aberdeen Varicose Vein Questionnaire (AVVQ), the World Health Organization Quality of Life–BREF (WHOQOL-BREF), and Individual Work Performance Questionnaire (IWPQ). Descriptive statistics, t-tests, ANOVA, chi-square, and correlation were used for analysis. Ethical approval for this study was obtained from the Institutional Review Board of Princess Nourah bint Abdulrahman University (IRB Log Number: 25-0008). Results: The prevalence of VVs was 18.8%. Male gender, prolonged static postures, and obesity were significantly associated with higher VV rates (p < 0.05). Logistic regression identified gender as the only independent predictor of VV presence (p < 0.001). Participants with VVs reported significantly lower QoL across all WHOQOL domains and reduced work performance scores. Two-way ANOVA showed a significant main effect of gender on work performance (p = 0.002), while VV status and occupation showed no significant interaction effects. VV severity was negatively correlated with job performance (r = −0.138, p = 0.006), while QoL positively correlated with performance (r = 0.149, p = 0.003). University faculty demonstrated significantly higher VV severity than schoolteachers (p = 0.013). Conclusions: It is concluded that the prevalence of varicose veins among teaching professionals in Saudi Arabia is associated with significantly lower quality of life and reduced work performance, highlighting the occupational impact of the condition. Preventive workplace interventions and further longitudinal research are recommended to confirm and expand these findings. Full article
(This article belongs to the Section Public Health and Preventive Medicine)
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13 pages, 1302 KB  
Review
Venous Manifestations of Gastric Cancer: Bilateral Varicose Veins as a Rare Initial Presentation—A Narrative Review
by Anna Laura Maiozzi, Filomena Botta, Silvia Maccioni, Livia Stanga, Lucretia Marin-Bancila, Ciprian Ilie Rosca, Anca Dinu, Abhinav Sharma and Nilima Rajpal Kundnani
Gastrointest. Disord. 2025, 7(4), 70; https://doi.org/10.3390/gidisord7040070 - 31 Oct 2025
Viewed by 1994
Abstract
Background: Varicose veins (VVs) are an overlying manifestation of chronic venous disease, commonly occurring in the lower extremities. While typically linked to primary venous insufficiency, they can occasionally be secondary to systemic disease, e.g., malignancies, by various mechanisms such as tumor compression, hypercoagulability, [...] Read more.
Background: Varicose veins (VVs) are an overlying manifestation of chronic venous disease, commonly occurring in the lower extremities. While typically linked to primary venous insufficiency, they can occasionally be secondary to systemic disease, e.g., malignancies, by various mechanisms such as tumor compression, hypercoagulability, and paraneoplastic syndromes. Bilateral varicose veins, as a presenting symptom of gastric cancer, are extremely rare and poorly documented. Materials and Methods: A comprehensive literature search was conducted to identify reports and studies linking varicose veins and malignancies, with particular focus on gastric cancer. The search was performed using the PubMed, Scopus, and Web of Science databases covering the last 13 years. Results: Literature Review: A review of the literature in the past decade identified publications, mostly case reports, describing associations between varicose-like venous changes and malignancies such as gastric, pancreatic, hepatic, and small-bowel tumors. The predominant mechanisms reported were inferior vena cava obstruction, tumor-related thrombosis, and paraneoplastic migratory superficial thrombophlebitis (Trousseau’s syndrome). Only a few cases involved gastric cancer as the primary site, with venous changes often being the first clinical sign. There is limited experience with gastric cancer that presents alongside bilateral collateral or varicose veins initially. Apart from the various reports having malignancies and varicose veins we also describe the case of a 50-year-old man who had extended history of bilateral lower-limb varicose veins. Severe, unexplained anaemia without obvious bleeding was discovered during examination. A biopsy verified a gastric adenocarcinoma, while upper gastrointestinal endoscopy revealed an ulcerated mass on the stomach’s greater curvature. Peritoneal dissemination was discovered with additional staging. A palliative subtotal gastrectomy was carried out because of the patient’s ongoing anaemia and suspected chronic bleeding caused by the tumour. The venous symptoms preceded any gastrointestinal issues. Conclusions: Although uncommon, malignancy should be considered in the differential diagnosis for atypical or rapidly progressing bilateral varicose veins, especially when accompanied by systemic symptoms or lab results such as unexplained anemia. Increased suspicion may lead to earlier cancer detection in some patients. Full article
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11 pages, 2216 KB  
Article
Innovative Approach to Embolization of Pelvic Varices Using Endovaginal Guidance: Methodology and Early Outcomes
by Eva Fourage-Jambon, Rayann Soueidan, Hamza Sawalha, Yassine Lamfichekh, Benjamin Linares, Hugo Hans, Mathieu David, Isabelle Molina-Andreo, Charlotte Douchez, Nicolas Pangon, Yann Le Bras, Rim Maaloum and Clément Marcelin
J. Pers. Med. 2025, 15(10), 500; https://doi.org/10.3390/jpm15100500 - 17 Oct 2025
Cited by 1 | Viewed by 1394
Abstract
Objective: To retrospectively assess the safety and efficacy of endovaginal guidance for embolizing perivaginal varices associated with persistent localized symptoms, including dyspareunia and postcoital pain. Methods: From February 2024 to January 2025, 10 women (median age: 36 years, range: 23–45) underwent pelvic embolization [...] Read more.
Objective: To retrospectively assess the safety and efficacy of endovaginal guidance for embolizing perivaginal varices associated with persistent localized symptoms, including dyspareunia and postcoital pain. Methods: From February 2024 to January 2025, 10 women (median age: 36 years, range: 23–45) underwent pelvic embolization using endovaginal guidance. Eight patients had already undergone endovascular embolization, with persistent perivaginal varices that were inaccessible by this approach, accompanied by dyspareunia or postcoital pain. Primary efficacy was assessed three months post-embolization, defined as a Visual Analog Scale (VAS) score of <2 and a ≥50% decrease. Outcomes were assessed through clinical and imaging follow-up. Results: Technical efficacy was achieved in all procedures (100%). Embolization was performed using Glubran/Lipiodol in eight cases (80%) and Onyx® in two cases (20%). The primary efficacy of the procedures was 90.0% (9 out of 10 cases). A reduction in dyspareunia and postcoital pain was observed, with median VAS scores decreasing to one and zero, respectively, compared to initial scores of seven and seven (p = 0.002 and p = 0.016) and to scores after endovascular embolization to five and five (p = 0.004 and p = 0.016). No major complications were recorded. Imaging follow-up showed a significant reduction in perivaginal varicosities in all cases. Conclusions: Endovaginal guidance proves to be a fast and effective technique for the embolization of perivaginal varices, highlighting its integration into the principles of personalized medicine. Full article
(This article belongs to the Special Issue Exploring Interventional Radiology: New Advances and Prospects)
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25 pages, 6148 KB  
Article
Sex-Specific Gene Expression Differences in Varicose Veins
by Mariya A. Smetanina, Valeria A. Korolenya, Ksenia S. Sevostyanova, Konstantin A. Gavrilov, Fedor A. Sipin, Andrey I. Shevela and Maxim L. Filipenko
Biomedicines 2025, 13(10), 2373; https://doi.org/10.3390/biomedicines13102373 - 27 Sep 2025
Viewed by 1495
Abstract
Background/Objectives: There is clear evidence for the higher prevalence of varicose veins (VVs) among women. In this regard, the research on sex differences affecting this condition is very important for sex-specific health care. We aimed to assess how male or female sex [...] Read more.
Background/Objectives: There is clear evidence for the higher prevalence of varicose veins (VVs) among women. In this regard, the research on sex differences affecting this condition is very important for sex-specific health care. We aimed to assess how male or female sex may contribute to the changes to gene expression profiles in the vein wall during varicose transformation. Methods: Paired varicose vein (VV) and non-varicose vein (NV) segments were harvested from patients with VVs after venous surgery. Processed RNAs from those samples were subjected to gene expression analysis by reverse transcription quantitative polymerase chain reaction (RT-qPCR) followed by further data analysis. Multiple linear regression (MLR) analysis was performed to identify and characterize relationships among multiple factors (relative mRNA levels of a gene in NV or VV or their ratio, as dependent variables) and sex (independent variable, used individually or in combination with other patient’s characteristics). For sex-specific gene regulation analysis, all potential binding sites for sex hormone receptors were identified in each gene’s regulatory region sequence. Results: Using the independent method and a replicative patient sample set, we validated our previous data on 23 genes’ differential expression in VVs and obtained insights on their sex-specific regulation. Sex (as an individual independent variable or in combination with other parameters—patient characteristics such as Age, BMI, CEAP class, Height, VVD manifestation and duration) was a moderate predictor (0.40 < R < 0.59; p (R) < 0.05) for the STK38L expression in VVs (with its higher mRNA level in NVs and VVs of women compared to men); sex was a strong predictor (0.6 < R < 0.79; p (R) < 0.05) for the TIMP1 expression in VVs (with its lower mRNA level in VVs of women compared to men); sex was a moderate predictor (0.40 < R < 0.59; p (R) < 0.05) for the EBF1 expression in NVs (with its lower mRNA level in NVs of women compared to men). Conclusions: Confirmed differential expression of the studied genes in VVs indicates their plausible participation in vein wall remodeling. Sex-specific expression in veins for the subset of those genes suggests their hormonal regulation as well as other mechanisms involved in VV pathogenesis. This work enriches our understanding of sex features for the development of VVs and may provide the foundation for future investigations and beneficial treatment options. Full article
(This article belongs to the Special Issue Unveiling the Genetic Architecture of Complex and Common Diseases)
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29 pages, 1993 KB  
Review
How Can Molecules Induce Hemorrhoids? The Role of Genetics and Epigenetics in Hemorrhoidal Disease
by Barbara Parol, Oliwia Sas, Mateusz Mazurek, Krzysztof Data, Slawomir Wozniak and Zygmunt Domagala
Int. J. Mol. Sci. 2025, 26(19), 9394; https://doi.org/10.3390/ijms26199394 - 26 Sep 2025
Cited by 4 | Viewed by 4144
Abstract
The pathophysiology of hemorrhoids remains elusive; however, recent research has increasingly focused on the role of genetic and epigenetic mechanisms in this condition, offering prospects for targeted treatments. We conducted a review using PubMed, Embase, and Google Scholar, supplemented by citation searching, to [...] Read more.
The pathophysiology of hemorrhoids remains elusive; however, recent research has increasingly focused on the role of genetic and epigenetic mechanisms in this condition, offering prospects for targeted treatments. We conducted a review using PubMed, Embase, and Google Scholar, supplemented by citation searching, to summarize the current knowledge of the involvement of genetic and epigenetic mechanisms in hemorrhoids. Our review of 250 papers suggests that several genes, including FOXC2, NOX, NOS, and CALM3, may be responsible for the predisposing changes leading to the development of hemorrhoids. These genes have been associated with varicose veins, inflammation, and connective tissue alterations. Additionally, epigenetic mechanisms, particularly those mediated by miRNA, have been implicated in the clinical symptoms of hemorrhoids. While epigenetic regulation may influence inflammation, dilated vessels, and connective tissue degeneration, the exact mechanisms involved in these processes remain unclear. Furthermore, certain predisposing factors for hemorrhoids appear to involve both genetic and epigenetic mechanisms. This knowledge contributes to a better understanding of hemorrhoids and holds promise for developing novel therapeutic approaches. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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24 pages, 3791 KB  
Article
Defined Composition of Culture Media Promotes Rodent Neonatal Cardiomyocyte Maturation and Enables Functional Neuro-Cardiac Co-Culture
by Giulia Borile, Lolita Dokshokova, Nicola Moro, Antonio Campo, Valentina Prando, Jose L. Sanchez-Alonso, Julia Gorelik, Giuseppe Faggian, Marco Mongillo and Tania Zaglia
Cells 2025, 14(18), 1434; https://doi.org/10.3390/cells14181434 - 13 Sep 2025
Viewed by 4763
Abstract
Neonatal rodent cardiomyocytes (CMs) are a mainstay of in vitro cardiac research, yet their immature phenotype limits the study of key physiological processes such as excitation–contraction coupling (ECC) and sympathetic modulation. Here, we present a defined low-glucose, serum-free (LGSF) culture protocol that drives [...] Read more.
Neonatal rodent cardiomyocytes (CMs) are a mainstay of in vitro cardiac research, yet their immature phenotype limits the study of key physiological processes such as excitation–contraction coupling (ECC) and sympathetic modulation. Here, we present a defined low-glucose, serum-free (LGSF) culture protocol that drives the structural and functional maturation of neonatal CMs and supports their integration into functional neuro-cardiac co-cultures. After 15 days in LGSF conditions, CMs exhibit elongated morphology, organized sarcomeres, polarized connexin-43, mitochondrial redistribution, and sarcoplasmic reticulum (SR) development, all closely resembling features of adult cells. These structural hallmarks were paralleled by enhanced Ca2+ handling, with increased SR contribution and reduced spontaneous activity, indicative of a mature ECC phenotype. When co-cultured with sympathetic neurons (SN), CMs established anatomically distinct neuro-cardiac junctions. Notably, nicotine stimulation triggered spatially restricted, reversible increases in CM Ca2+ transients, confined to varicosity-contacted cells. Pharmacological analysis revealed subtype-specific roles for β1- and β2-adrenergic receptors, and uncovered evidence of functional crosstalk between them. Our study defines a reproducible culture framework that advances CM maturation and enables the high-resolution interrogation of synaptic-like sympathetic modulation. This approach opens new avenues for mechanistic studies and drug testing in developmentally relevant neuro-cardiac systems. Full article
(This article belongs to the Section Cells of the Cardiovascular System)
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11 pages, 6513 KB  
Article
Age- and Varicose Disease-Associated Changes in the Muscular Components of the Great Saphenous Vein
by Khurshed A. Abduvosidov, Irina A. Chekmareva, Valeria G. Shestakova, Irina N. Shabanova, Alexander G. Alekseev, Edgar S. Kafarov, Alexander A. Palalov, Irina N. Yashina and Evgeny N. Galeysya
J. Clin. Med. 2025, 14(18), 6448; https://doi.org/10.3390/jcm14186448 - 12 Sep 2025
Viewed by 1085
Abstract
Varicose disease and other age-related vascular illnesses are extremely prevalent among the adult population. Despite this, research devoted to involutive changes in the veins of the lower extremities is rare and fragmented. Complex morphological evaluation of the wall of the vein related to [...] Read more.
Varicose disease and other age-related vascular illnesses are extremely prevalent among the adult population. Despite this, research devoted to involutive changes in the veins of the lower extremities is rare and fragmented. Complex morphological evaluation of the wall of the vein related to age and varicose disease can add valuable data to fundamental geriatric and vascular medicine. Objectives: The study was designed to determine the age-related changes in the muscular component of the great saphenous vein and changes associated with varicose disease. Materials and Methods: A morphological study of a specimen of the great saphenous vein was conducted on 55 deceased individuals and 80 patients with varicose disease. Four age subgroups were identified: young, middle-aged, elderly, and senile. A total of 135 fragments of the great saphenous vein were evaluated. Histological, morphometric, and electron microscopic studies were performed. A quantitative analysis of the volumetric fraction of muscular components was calculated using the Shapiro–Wilk test, Kruskal–Wallis (ANOVA) and Mann–Whitney methods with Bonferroni correction. Results: Our study showed that the amount of connective tissue elements between bundles of smooth muscle cells increased with age. In patients with varicose disease, we observed an appearance of connective tissue fibers among smooth muscle cells, more pronounced with the disease progression. The structure of smooth muscle cell changes. Thus, we observed hypertrophy and phenotypic heterogeneity of cells with subsequent destruction of communicative contacts. The values of subintimal longitudinally arranged smooth muscle cells reached their maximum in middle age in both normal and varicose veins, while significant decrease occurred in elderly and senile patients. Quantitative indicators of circularly arranged smooth muscle cells of the middle layer did not change with age but significantly decreased in varicose disease. Age-related changes are characterized by an increase in the proportion of smooth muscle cells in the outer layer. In varicose veins, in young and middle-aged patients, the content of bundles of longitudinally arranged smooth muscle cells in the outer layer was higher compared to the age norm, with a significant decrease in senile age. Conclusions: The age norm of the muscular component of the great saphenous vein wall is characterized by an increase in the volumetric fraction of subintimal longitudinally arranged smooth muscle cells in middle age, the volumetric fraction of circularly arranged smooth muscle cells of the middle layer remains unchanged, and the volumetric fraction of bundles of longitudinally arranged myocytes of the outer layer increases. With age in varicose disease, sclerotic changes progress in the structure of the great saphenous vein at the tissue, cellular, and intracellular levels, leading to a decrease in the volumetric fraction of all muscular components of the great saphenous vein structure. Full article
(This article belongs to the Section Vascular Medicine)
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27 pages, 2263 KB  
Article
Molecular Signatures Related to Inflammation and Angiogenesis in Patients with Lower Extremity Artery Disease, Abdominal Aortic Aneurysm, and Varicose Veins: Shared and Distinct Pathways
by Daniel Zalewski, Paulina Chmiel, Przemysław Kołodziej, Marcin Feldo, Andrzej Stępniewski, Marta Ziaja-Sołtys, Joanna Łuszczak, Agata Stanek, Janusz Kocki and Anna Bogucka-Kocka
Int. J. Mol. Sci. 2025, 26(18), 8786; https://doi.org/10.3390/ijms26188786 - 9 Sep 2025
Cited by 1 | Viewed by 1437
Abstract
Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and varicose veins (VV) are frequently underdiagnosed and undertreated peripheral vascular diseases that pose considerable public health challenges. More research is required to elucidate the pathophysiological mechanisms underlying these conditions and to identify novel [...] Read more.
Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and varicose veins (VV) are frequently underdiagnosed and undertreated peripheral vascular diseases that pose considerable public health challenges. More research is required to elucidate the pathophysiological mechanisms underlying these conditions and to identify novel diagnostic and therapeutic biomarkers. Therefore, in our study, we aimed to identify shared and distinct pathways associated with angiogenesis and inflammation in LEAD, AAA, and VV. The expression of 18 genes in peripheral blood mononuclear cells and the plasma levels of six proteins were compared between groups of 40 patients with LEAD, 40 patients with AAA, and 40 patients with VV. Independent RNA-seq and microRNA-seq data were integrated to predict differentially expressed transcription factors and microRNAs associated with the most significant genes. Gene Ontology functional analysis was performed to determine the potential biological effects of the observed dysregulations. The elevated expression of VEGFB and TGFB1, along with increased plasma levels of VEGF-C and reduced plasma levels of VEGF-A, were distinguishing features of patients with LEAD compared to those with AAA and VV. Decreased plasma levels of TGF-alpha and TGF-beta 1 were found to be indicative of varicose veins compared to individuals with arterial diseases (LEAD and AAA). Transcription factors and microRNAs potentially regulating the obtained signatures were identified and integrated into a hypothetical regulatory network. The observed dysregulations were found to be functionally associated with the response to hypoxia, the positive regulation of angiogenesis, chemotaxis, vascular permeability, and cell adhesion. The presented study identified dysregulations of key angiogenesis- and inflammation-related factors in peripheral blood mononuclear cells and plasma between LEAD, AAA, and VV patients, providing new insights into the shared and distinct molecular mechanisms underlying these diseases. Full article
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