Special Issue "New Perspectives in Phlebology and Lymphology"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Vascular Medicine".

Deadline for manuscript submissions: closed (30 June 2021).

Special Issue Editor

Dr. Attilio Cavezzi
E-Mail Website
Guest Editor
Eurocenter Venalinfa, San Benedetto del Tronto (AP), Italy
Interests: phlebology; lymphology; longevity and translational medicine; hormesis; psychoneuroendocrineimmunology; mitochondria

Special Issue Information

Dear Colleagues,

Venous and lymphatic diseases are extremely diffused in the general population, with a broad spectrum that ranges from tiny telangiectasias and varices to venous ulcers, thromboembolisms, and lymphedemas, to name just a few.

The pathophysiology and diagnostics of veins and lymphatics are currently undergoing a significant reappraisal due to the most recent scientific updates. Similarly, new evidence-based treatments are regularly being proposed for varicose vein disease, deep and superficial vein thrombosis, leg venous ulcer, and lymphedema and its complications.

In view of this re-assessment of our phlebolymphology knowledge, we welcome innovative science-backed cultural contributions that expand the horizons of these interesting medical disciplines. Venous and lymphatic components play an important role in most chronic degenerative diseases and, more generally, in biomedical science; hence, a translational medicine approach is also favored.

In this Special Issue, it is our intention to present a collection of pertinent, stimulating, and visionary articles containing scientific proposals on the basic science and diagnostics of, and treatments for, venous and lymphatic diseases. We particularly welcome high-level original research articles that shed light on future research directions in phlebology and lymphology. Ultimately, this Special Issue represents a unique opportunity to disseminate innovative scientific contributions via a high-level journal to a great number of clinicians worldwide.

Dr. Attilio Cavezzi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • veins
  • lymphatics
  • phlebology
  • lymphology
  • varicose veins
  • telangiectasias
  • vein thrombosis
  • thromboembolism
  • post-thrombotic syndrome
  • venous ulcer
  • lymphedema
  • erysipelas
  • lipedema
  • duplex ultrasound
  • phlebography
  • lymphoscintigraphy
  • sclerotherapy
  • sclerosant foam
  • endovenous thermal ablation
  • varicose vein surgery
  • compression therapy
  • venous stent
  • anticoagulants
  • thromboprophylaxis
  • thrombolysis
  • complex decongestive treatment
  • drugs
  • nutraceuticals
  • integrative medicine

Published Papers (9 papers)

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Research

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Article
The Number of Pregnancies and Deliveries and Their Association with Selected Morphological and Hemodynamic Parameters of the Pelvic and Abdominal Venous System
J. Clin. Med. 2021, 10(4), 736; https://doi.org/10.3390/jcm10040736 - 12 Feb 2021
Cited by 2 | Viewed by 659
Abstract
Background: Although pregnancy has been identified as one of the risk factors for venous disease, the mechanism of this interaction remains unclear. Possibly, pregnancy results in overstrain and vein dilatation, which exceed their durability and persist after pregnancy. The aim of this study [...] Read more.
Background: Although pregnancy has been identified as one of the risk factors for venous disease, the mechanism of this interaction remains unclear. Possibly, pregnancy results in overstrain and vein dilatation, which exceed their durability and persist after pregnancy. The aim of this study was the assessment of the relationship between the number of pregnancies in women with venous disease and the selected parameters of their venous systems. Patients and methods: The retrospective assessment concerned 518 patients subjected to the diagnostics of the venous system in the lower limbs and the abdomen/pelvis using ultrasound scan and magnetic resonance or computed tomography. Results: We found that the occurrence of pelvic venous symptoms increases proportionally to the number of pregnancies and is correlated with ovarian and parauterine vein dilatation/incompetence (e.g., 13.5% of nulliparous women reported pelvic pain, and reflux in left ovarian veins was detected in 21.4% of the patients from that group, whereas in women after two pregnancies, pain and reflux concerned 22.8% and 90.6% of patients, respectively). In the nulliparous group, the development of venous disease resulted from the presence of anatomic abnormalities in abdominal/pelvic veins. Conclusions: Our report proved that the number of pregnancies is correlated with the incidence of pelvic vein insufficiency. Although not specifically addressed in this study, some correlation was found with saphenous disease as well. However, further studies are necessary to provide more evidence about the role of pelvic vein insufficiency in chronic venous disease of the lower limbs. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
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Article
Hemodynamic and Radiological Classification of Ovarian Veins System Insufficiency
J. Clin. Med. 2021, 10(4), 646; https://doi.org/10.3390/jcm10040646 - 08 Feb 2021
Cited by 1 | Viewed by 578
Abstract
Ovarian veins system insufficiency is one of the most common reasons for pelvic venous insufficiency (PVI). PVI is a hemodynamic phenomenon responsible for the occurrence of venous insufficiency of the lower extremities and recurrent varicose veins in nulliparous and parous women, as well [...] Read more.
Ovarian veins system insufficiency is one of the most common reasons for pelvic venous insufficiency (PVI). PVI is a hemodynamic phenomenon responsible for the occurrence of venous insufficiency of the lower extremities and recurrent varicose veins in nulliparous and parous women, as well as for a set of symptoms described as pelvic congestion syndrome (PCS). In the years 2017–2019, 535 patients admitted to our center with symptoms of venous insufficiency of the lower extremities, underwent complete ultrasound diagnostics (color-duplex ultrasound) of the venous system of the abdomen, pelvis and lower limbs, as well as extended imaging diagnostics using computed tomography (CT) or magnetic resonance (MR) venography. On the basis of the obtained results, the authors proposed a 4-grade hemodynamic and radiological classification (grades I-IV) defining the stratification of ovarian veins insufficiency. Using the above mentioned classification approx. 32% patients were identified as Grade I and I/II, approximately 35% revealed morphological and hemodynamic changes corresponding to Grade II and II/III, approximately 25% were classified as Grade III, whereas the remaining 8% were assessed as Grade IV. The described classification allows for the grading of ovarian veins insufficiency based on transparent radiological criteria, making it easy to use in everyday clinical practice. According to the authors, the proposed classification could facilitate communication between diagnostic physicians, specialists dealing with the treatment of venous insufficiency and gynecologists, who admit patients with symptoms suggesting venous insufficiency of the pelvis. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
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Article
Two-Year Follow-Up after Endovenous Closure with Short-Chain Cyanoacrylate versus Laser Ablation in Venous Insufficiency
J. Clin. Med. 2021, 10(4), 628; https://doi.org/10.3390/jcm10040628 - 07 Feb 2021
Viewed by 562
Abstract
Background: The current treatment of venous disease is focused on the minimally invasive exclusion of the affected vein. Besides widely used thermal ablation, chemical ablation with cyanoacrylate, reported as safe and highly effective, has been gaining increasing interest. Patients and methods: In the [...] Read more.
Background: The current treatment of venous disease is focused on the minimally invasive exclusion of the affected vein. Besides widely used thermal ablation, chemical ablation with cyanoacrylate, reported as safe and highly effective, has been gaining increasing interest. Patients and methods: In the current report, we present data from a two-year observation in 89 patients (61 female/28 male, mean age 44.3 ± 13.5) suffering from venous insufficiency (C2–C4), treated either using short-chain cyanoacrylate, the VenaBlock system (n = 43) or laser thermoablation with ELVeS 1470 (n = 46). The assessment comprised the occurrence of venous disease-related symptoms and the ultrasound examination of the leg venous system. Results: The frequency of recanalization after 2 years from the VenaBlock procedure was significantly higher than after laser treatment (37.2 vs. 8.7%). Apart from recanalization, in some individuals from both groups, the symptoms of recurrence and/or disease progression, including the development of insufficiency in other veins of treated or contralateral legs (9.3 vs. 15.2% and 9.3 vs. 17.4%, respectively), were observed. Unexpectedly, the general prevalence of the disease progression did not differ significantly between the VenaBlock and ELVeS groups (44.2 vs. 34.8%, respectively). Conclusions: Despite the higher recanalization rate of VenaBlock compared to ELVeS, the overall effectiveness of cyanoacrylate and laser thermoablation after two years was similar. Therefore, both methods similarly failed to prevent recurrence and disease progression, which seem to be method-independent. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
Article
The Analysis of Selected Morphological and Hemodynamic Parameters of the Venous System and Their Presumable Impact on the Risk of Recurrence after Varicose Vein Treatment
J. Clin. Med. 2021, 10(3), 455; https://doi.org/10.3390/jcm10030455 - 25 Jan 2021
Cited by 3 | Viewed by 502
Abstract
Introduction: The current treatment of venous disease is focused on reflux elimination in main venous trunks, especially in the saphenous vein. However, a high recurrence rate, independent of the method of treatment, suggests that the reason of low effectiveness may be due to [...] Read more.
Introduction: The current treatment of venous disease is focused on reflux elimination in main venous trunks, especially in the saphenous vein. However, a high recurrence rate, independent of the method of treatment, suggests that the reason of low effectiveness may be due to a strategy focused on symptoms, without considering their origin. Method: The aim of study was the comparison of retrospective data from 535 women with venous disease, either after treatment (n = 183) or not treated before (n = 352). The analysis concerned clinical symptoms and the results of the extended diagnostics, including the examination of the lower limb, pelvic and abdominal veins either using duplex-doppler ultrasound as well as venography with computed tomography or magnetic resonance. Results: The comparison of selected venous system parameters revealed more advanced disease progression in previously treated patients, compared to non-treated individuals (e.g., ipsi- or bilateral incompetence of sapheno-phemoral junction—29.5% vs. 20.4%, at P < 0.05 and 13.6% vs. 7.7% at P < 0.05, respectively). This difference could be explained by post-treatment alterations in the venous system, an older age and the higher number of pregnancies in the recurrence group. However, both groups did not differ in regards to the symptoms of pelvic venous insufficiency or the frequency of relevant variants/abnormalities in venous system. Conclusions: Based on the aforementioned findings, we postulate the revision of treatment strategy, which should consider abdominal and pelvic veins as the source of reflux in many female subjects. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
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Article
Venous Thromboembolism Prophylaxis and Thrombotic Risk Stratification in the Varicose Veins Surgery—Prospective Observational Study
J. Clin. Med. 2020, 9(12), 3970; https://doi.org/10.3390/jcm9123970 - 07 Dec 2020
Cited by 2 | Viewed by 688
Abstract
Background: An invasive phlebological treatment is still not free from complications such as thrombosis. As in other surgical populations, not only the treatment modality, but also patient condition-related venous thromboembolism (VTE) risk factors matter. The current protocols used in varicose vein surgery centers [...] Read more.
Background: An invasive phlebological treatment is still not free from complications such as thrombosis. As in other surgical populations, not only the treatment modality, but also patient condition-related venous thromboembolism (VTE) risk factors matter. The current protocols used in varicose vein surgery centers are based mostly on individual risk assessment as well as on an implementation and extrapolation of general surgery VTE prophylaxis guidelines. In the presented study, the efficacy of routine VTE pharmacological thromboprophylaxis in patients undergoing saphenous varicose vein surgery was prospectively evaluated. In the result assessment, VTE risk factor evaluation and Caprini score results were included; however, due to the limited size of the projected study group, as well as expected limited deep vein thrombosis (DVT) prevalence in this clinical scenario, it was not possible to perform the validation of the Caprini model efficacy in the projected study model. Methods: In the study, 141 patients undergoing saphenous vein stripping and miniphlebectomy in spinal anesthesia were included. In all of the patients, VTE risk factors (including Caprini score evaluation) were assessed, and the routine thromboprophylaxis with enoxaparin 40 mg for 10 days was used. The venous ultrasounds were undertaken before the surgery and on the 10th and 30th day after surgery. The study endpoint was the presence of symptomatic or asymptomatic DVT confirmed in the imaging study. The study safety endpoint was major bleeding occurrence intraoperatively or within 30 days after surgery. Results: The presence of a postoperative DVT was diagnosed in five cases (3.5%) In all of these cases, only distal DVT was confirmed. Despite extensive saphenous varicose vein surgery with stripping and miniphlebectomy performed in nontumescent but spinal anesthesia, no proximal lower leg episode was diagnosed. Three out of five DVT cases were diagnosed on day 10 postoperative control, while a further two were confirmed in the ultrasound examination performed 30 days after procedure. No clinically documented pulmonaly embolism (PE) as well as no bleeding episodes were noticed. Among the factors related to the statistically significant higher DVT occurrence, the results of the Caprini score were identified with odds ratio (OR) = 2.04 (95% CI = (0.998; 4.18)). Another factor that became statistically significant in terms of the higher postoperative DVT prevalence was the reported Venous Clinical Severity Score (VCSS) results (OR = 1.98; 95% CI (1.19; 3.26)). In the multiple logistic regression analysis, the patient age (OR = 0.86; 95% CI (0.75–0.99)), Caprini score evaluation results (OR = 4.04; 95% CI (1.26–12.9)) and VCSS results (OR = 2.4; 95% CI (1.23–4.7)) were of statistical significance as predictors for postoperative DVT occurrence, with a p value of 0.029 for age, and p = 0.017 and p = 0.009 for Caprini score results and VCSS results, respectively. Due to the confirmed limited number of the DVT events in our study cohort, as well as the descriptive and explorative nature of the achieved results, the final clinical potential and significance of the identified parameters, including Caprini score rate and VCSS rate, should be interpreted with caution and studied in the further trials in these clinical settings. Conclusion: All the patients undergoing varicose vein surgery should undergo VTE risk evaluation based on the individual assessment. In VTE risk evaluation, patient and surgical procedure characteristics based on the factors included into the Caprini score but also on specific chronic venous disease-related factors should be taken into consideration. Further studies are needed to propose an objective and validated VTE risk assessment model, as well as a validated antithrombotic prophylaxis protocol in this particular patient group. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
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Article
Compression Therapy Is Not Contraindicated in Diabetic Patients with Venous or Mixed Leg Ulcer
J. Clin. Med. 2020, 9(11), 3709; https://doi.org/10.3390/jcm9113709 - 19 Nov 2020
Cited by 1 | Viewed by 700
Abstract
The aim of this study was to investigate if compression therapy (CT) can be safely applied in diabetic patients with Venous Leg Ulcers (VLU), even when a moderate arterial impairment (defined by an Ankle-Brachial Pressure Index 0.5–0.8) occurs as in mixed leg ulcers [...] Read more.
The aim of this study was to investigate if compression therapy (CT) can be safely applied in diabetic patients with Venous Leg Ulcers (VLU), even when a moderate arterial impairment (defined by an Ankle-Brachial Pressure Index 0.5–0.8) occurs as in mixed leg ulcers (MLU). Materials and methods: in one of our previous publications we compared the outcomes of two groups of patients with recalcitrant leg ulcers. Seventy-one patients were affected by mixed venous and arterial impairment and 109 by isolated venous disease. Both groups were treated by tailored inelastic CT (with compression pressure <40 mm Hg in patients with MLU and >60 mm Hg in patients with VLU) and ultrasound guided foam sclerotherapy (UGFS) of the superficial incompetent veins with the reflux directed to the ulcer bed. In the present sub analysis of the same patients we compared the healing time of 107 non-diabetic patients (NDP), 69 with VLU and 38 with MLU) with the healing time of 73 diabetic patients (DP), 40 with VLU and 33 with MLU. Results: Twenty-five patients were lost at follow up. The results refer to 155 patients who completed the treatment protocol. In the VLU group median healing time was 25 weeks for NDP and 28 weeks in DP (p = 0.09). In the MLU group median healing time was 27 weeks for NDP and 29 weeks for DP (p = −0.19). Conclusions: when providing leg ulcer treatment by means of tailored compression regimen and foam sclerotherapy for superficial venous refluxes, diabetes has only a minor or no effect on the healing time of recalcitrant VLU or MLU. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
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Article
Shaving Technique and Compression Therapy for Elephantiasis Nostras Verrucosa (Lymphostatic Verrucosis) of Forefeet and Toes in End-Stage Primary Lymphedema: A 5 Year Follow-Up Study in 28 Patients and a Review of the Literature
J. Clin. Med. 2020, 9(10), 3139; https://doi.org/10.3390/jcm9103139 - 28 Sep 2020
Cited by 1 | Viewed by 490
Abstract
Background. Longstanding lymphedema can lead, especially when there is recurrence of erysipelas, to irreversible elephantiasis nostras verrucosa (ENV). This predisposes to new episodes of erysipelas, leading to further damage of the lymphatics and deterioration of the lymphedema as a whole. We report the [...] Read more.
Background. Longstanding lymphedema can lead, especially when there is recurrence of erysipelas, to irreversible elephantiasis nostras verrucosa (ENV). This predisposes to new episodes of erysipelas, leading to further damage of the lymphatics and deterioration of the lymphedema as a whole. We report the results of 28 patients with primary lymphedema and surgical removal ENV of the forefoot and toes treated between 2006 and 2014. Method: Retrospective descriptive 5 year follow-up study of 28 patients with various diagnosis of primary lymphedema. Wound healing time, number of erysipelas, body mass index (BMI), recurrence of EVN and types of compression were documented during follow-up. Results: After preoperative multidisciplinary work up, operation of the toes with shaving and excision was performed within a conservative treatment program. During the follow up, the number of erysipelas attacks decreased dramatically (mean 17.6 vs. 0.6). Before treatment, no toecaps were used; and in follow up, it was a part of treatment. Recurrence of ENV was not observed. Compared to the literature with often BMI > 35, the mean BMI in our group was 30.0 (overweight). In 12 patients, we concurrently performed circumferential suction-assisted lipectomy for end-stage lymphedema of the leg. Conclusion: Although lymphedema patients are treated with garments during the maintenance phase, compression of the toes is often too challenging. Surgical removal of the verrucosis of toes is an effective therapeutic modality as part of an integrated lymphedema treatment program to restore the shape of the toes and enable the wearing of toecaps. This technique can also be effective for ENV of origins other than primary lymphedema. Although ENV is a generally accepted term, it can have undesirable connotations. We suggest using a more inclusive name such as lymphostatic verrucosis, because long-lasting lymphatic impairment is involved in all ENV and the term verrucosis is above discussion. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
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Review

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Review
Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management
J. Clin. Med. 2021, 10(15), 3239; https://doi.org/10.3390/jcm10153239 - 22 Jul 2021
Viewed by 212
Abstract
Chronic venous disease (CVD) is a multifactorial condition affecting an important percentage of the global population. It ranges from mild clinical signs, such as telangiectasias or reticular veins, to severe manifestations, such as venous ulcerations. However, varicose veins (VVs) are the most common [...] Read more.
Chronic venous disease (CVD) is a multifactorial condition affecting an important percentage of the global population. It ranges from mild clinical signs, such as telangiectasias or reticular veins, to severe manifestations, such as venous ulcerations. However, varicose veins (VVs) are the most common manifestation of CVD. The explicit mechanisms of the disease are not well-understood. It seems that genetics and a plethora of environmental agents play an important role in the development and progression of CVD. The exposure to these factors leads to altered hemodynamics of the venous system, described as ambulatory venous hypertension, therefore promoting microcirculatory changes, inflammatory responses, hypoxia, venous wall remodeling, and epigenetic variations, even with important systemic implications. Thus, a proper clinical management of patients with CVD is essential to prevent potential harms of the disease, which also entails a significant loss of the quality of life in these individuals. Hence, the aim of the present review is to collect the current knowledge of CVD, including its epidemiology, etiology, and risk factors, but emphasizing the pathophysiology and medical care of these patients, including clinical manifestations, diagnosis, and treatments. Furthermore, future directions will also be covered in this work in order to provide potential fields to explore in the context of CVD. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
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Review
Medicine and Phlebolymphology: Time to Change?
J. Clin. Med. 2020, 9(12), 4091; https://doi.org/10.3390/jcm9124091 - 18 Dec 2020
Cited by 4 | Viewed by 1490
Abstract
Biomedical science is undergoing a reappraisal of its scientific advancement process and of the related healthcare management. Progress in medicine should combine improvements of knowledge, efficacy, and safety of diagnostic/therapeutic procedures, with adequate cost-effectiveness profiles. This narrative review is aimed at assessing in [...] Read more.
Biomedical science is undergoing a reappraisal of its scientific advancement process and of the related healthcare management. Progress in medicine should combine improvements of knowledge, efficacy, and safety of diagnostic/therapeutic procedures, with adequate cost-effectiveness profiles. This narrative review is aimed at assessing in medicine, more specifically in phlebology and lymphology: (a) scientific literature possible biases, (b) the level of evidence, comprehensiveness, and cost-effectiveness of the main therapeutic options, and (c) the possible contribution of integrative and translational medicine. Current medical research may have cognitive biases, or industry-tied influences, which impacts clinical practice. Some reductionism, with an increasing use of drugs and technology, often neglecting the understanding and care of the root causative pathways of the diseases, is affecting biomedical science as well. Aging brings a relevant burden of chronic degenerative diseases and disabilities, with relevant socio-economic repercussions; thus, a major attention to cost-effectiveness and appropriateness of healthcare is warranted. In this scenario, costly and innovative but relatively validated therapies may tend to be adopted in venous and lymphatic diseases, such as varicose veins, leg venous ulcer, post-thrombotic syndrome, pelvic congestion syndrome, and lymphedema. Conversely, a more comprehensive approach to the basic pathophysiology of chronic venous and lymphatic insufficiency and the inclusion of pharmacoeconomics analyses would benefit overall patients’ management. Erroneous lifestyle and nutrition, together with chronic stress-induced syndromes, significantly influence chronic degenerative phlebo-lymphatic diseases. The main active epigenetic socio-biologic factors are obesity, dysfunctions of musculo-respiratory-vascular pumps, pro-inflammatory nutrition, hyperactivation of stress axis, and sedentarism. An overall critical view of the scientific evidence and innovations in phebolymphology could be of help to improve efficacy, safety, and sustainability of current practice. Translational and integrative medicine may contribute to a patient-centered approach. Conversely, reductionism, eminence/reimbursement-based decisional processes, patients’ lack of education, industry-influenced science, and physician’s improvable awareness, may compromise efficacy, safety, appropriateness, and cost-effectiveness of future diagnostic and therapeutic patterns of phlebology and lymphology. Full article
(This article belongs to the Special Issue New Perspectives in Phlebology and Lymphology)
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