Allogenic Adipose-Derived Stem Cells in Diabetic Foot Ulcer Treatment: Clinical Effectiveness, Safety, Survival in the Wound Site, and Proteomic Impact.

Although encouraging results of adipose-derived stem cell (ADSC) use in wound healing are available, the mechanism of action has been studied mainly in vitro and in animals. This work aimed to examine the safety and efficacy of allogenic ADSCs in human diabetic foot ulcer treatment, in combination with the analyses of the wound. Equal groups of 23 participants each received fibrin gel with ADSCs or fibrin gel alone. The clinical effects were assessed at four time points: days 7, 14, 21 and 49. Material collected during debridement from a subset of each group was analyzed for the presence of ADSC donor DNA and proteomic changes. The reduction in wound size was greater at all subsequent visits, significantly on day 21 and 49, and the time to 50% reduction in the wound size was significantly shorter in patients who received ADSCs. Complete healing was achieved at the end of the study in seven patients treated with ADSCs vs. one treated without ADSCs. One week after ADSC application, 34 proteins significantly differentiated the material from both groups, seven of which, i.e., GAPDH, CAT, ACTN1, KRT1, KRT9, SCL4A1, and TPI, positively correlated with the healing rate. We detected ADSC donor DNA up to 21 days after administration. We confirmed ADSC-related improvement in wound healing that correlated with the molecular background, which provides insights into the role of ADSCs in wound healing-a step toward the development of cell-based therapies.

Peanut contamination in food products: a real danger for allergic people?

Introduction: Allergy to peanut affects approximately 2% of children and in most cases persists throughout adult life. Seventeen peanut allergens have been identified so far and registered as "Ara h" molecules. Two of them, Ara h 1 and Ara h 3, are the most abundant proteins in the peanut extract. Since strict avoidance of peanut-containing food is the easiest way to prevent severe allergic reactions, manufacturers must label such products. However, consumers can still inadvertently be exposed to peanut allergens when foods become contaminated from processing lines shared with peanut products. Aim: To investigate whether food products with the label "may contain traces of peanuts", available on the Polish market, are actually contaminated with Ara h 1 and Ara h 3. Material and methods: Thirty food products with the label "may contain traces of peanuts", were purchased in Polish stores. Samples of the foods were analyzed by using Ara h 1/Ara h 3 ELISA kits. Results: Nearly one third of tested food products contained clinically relevant amounts of Ara h 1 and Ara h 3. The doses of both peanut allergens, when adjusted to the serving size of tested products, exceeded several times the eliciting dose 05 (the amount of the allergen, which is predicted to provoke a reaction in 5% of at-the-risk allergic population). Conclusions: Consumption of foods labelled as "may contain traces of peanuts" poses a significant risk for people allergic to peanuts. Physicians should advise their patients with peanut allergy to strictly avoid such products.

Longitudinal Evaluation of Biomarkers in Wound Fluids from Venous Leg Ulcers and Split-thickness Skin Graft Donor Site Wounds Treated with a Protease-modulating Wound Dressing.

Venous leg ulcers represent a clinical challenge and impair the quality of life of patients. This study examines impaired wound healing in venous leg ulcers at the molecular level. Protein expression patterns for biomarkers were analysed in venous leg ulcer wound fluids from 57 patients treated with a protease-modulating polyacrylate wound dressing for 12 weeks, and compared with exudates from 10 acute split-thickness wounds. Wound healing improved in the venous leg ulcer wounds: 61.4% of the 57 patients with venous leg ulcer achieved a relative wound area reduction of ≥ 40%, and 50.9% of the total 57 patients achieved a relative wound area reduction of ≥ 60%. Within the first 14 days, abundances of S100A8, S100A9, neutrophil elastase, matrix metalloproteinase-2, and fibronectin in venous leg ulcer exudates decreased significantly and remained stable, yet higher than in acute wounds. Interleukin-1ß, tumour necrosis factor alpha, and matrix metalloproteinase-9 abundance ranges were similar in venous leg ulcers and acute wound fluids. Collagen (I) α1 abundance was higher in venous leg ulcer wound fluids and was not significantly regulated. Overall, significant biomarker changes occurred in the first 14 days before a clinically robust healing response in the venous leg ulcer cohort.

Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial.

Many patients with venous leg ulcers do not reach complete healing with compression treatment alone, which is current standard care. This clinical trial HEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study, with the aim to evaluate the efficacy and safety of a new drug LL-37 for topical administration, in combination with compression therapy, in 148 patients suffering from hard-to-heal venous leg ulcers. The study had three arms, consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort. Patients had a mean age of 67.6 years, a median ulcer duration of 20.3 months, and a mean wound size at the time of randomization of 11.6 cm2 . Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (a wound area of at least 10 cm2 at randomization), which is a known negative prognostic factor for healing. The study drug was well tolerated and safe in both dose strengths. In summary, this clinical trial did not detect any significant differences in healing of venous lower leg ulcers in the entire study cohort comparing patients treated with LL-37 versus placebo. A subgroup analysis provided an interesting observation that LL-37 could offer a treatment benefit in patients with large ulcers, exigently warranting a further study adequately powered to statistically assess the treatment outcome in this patient group.

Exhaled breath condensates from healthy children induce cell death of in vitro cultured cells by activation of apoptosis.

INTRODUCTION: Exhaled breath condensate (EBC) is a liquefied air, containing a mixture of non-volatile compounds, reflecting pathophysiological status of the bronchopulmonary system. Therefore, EBC analysis may be useful in diagnostics and monitoring of various respiratory diseases. In previous studies it was found that EBC from asthmatic children contained several regulators of angiogenesis. In vitro experiments with EBCs from children with asthma revealed their weak influence on proliferation of various cells. Surprisingly, EBCs from healthy children led to apoptosis of all tested cells. AIM: To assess the expression of selected apoptosis-related proteins in human and murine cells exposed to EBC from healthy children. MATERIAL AND METHODS: EBCs from healthy children were added to cultures of murine endothelial cells (C166) or human lung fibroblasts (HLF) to induce their apoptosis. For proteome analysis the apoptosis pathway-specific protein microarrays were used. RESULTS: The homogenates from EBC-treated C166 cells contained low amounts of Hsp27, which correlated with their fast death. Contrary to C166, the lysates from EBC-treated fibroblasts displayed increased amounts of Hsp27, which correlated with delayed HLF response to the induction of apoptosis. Except for increased caspase-3 in EBC-treated HLF, none of the other apoptosis regulators revealed any significant changes in that analysis. CONCLUSIONS: The screening of apoptosis pathways with microarray technology allowed identification of two molecules, Hsp27 and caspase-3, involved in cellular response to EBC. However, the factor responsible for induction of the cytotoxic effect of EBC from healthy children still remains unknown.

Is the composition of exhaled breath condensate a key to explain the course of COVID-19 in children?

INTRODUCTION: The relative resistance of children to severe course of the novel coronavirus infection remains unclear. We hypothesized that there might be a link between this phenomenon and observation from our previous studies concerning an inhibitory or cytotoxic effect of exhaled breath condensate (EBC) on endothelial cell cultures in children. AIM: Since we could not find any data on the similar effect caused by EBC in adults, the aim of our study was to evaluate and compare the biological activity of EBC in adults and children in an experimental in vitro model. Furthermore, in order to identify a putative agent responsible for these properties of EBC in children, we attempted to analyse the composition of selected EBC samples. MATERIAL AND METHODS: The influence of EBC samples on metabolic activity of endothelial cell line C-166 was assessed using colorimetric tetrazolium salt reduction assay (MTT assay). Selected EBC samples were fractionated using size exclusion chromatography and subjected to mass spectrometry analysis. RESULTS: Exhaled breath condensates in healthy children, but not in adults, revealed a cytotoxic effect on in vitro cell cultures. This effect was most significant in condensate fraction, which contained a prominent 4.8 kDa peak in the mass spectra. CONCLUSIONS: Breath condensates of healthy children contain the factor which reveals the inhibitory/cytotoxic effect on endothelial cell cultures. Although the physiological role of this agent remains unclear, its identification may potentially be useful in ongoing research on SARS-CoV-2/COVID-19.

Influence of exhaled breath condensates from children with asthma on endothelial cells cultured in vitro. Do we really know everything about our breath condensate?

INTRODUCTION: Asthma-associated remodelling involves subepithelial fibrosis and increased vascularization of the bronchial wall. The latter may be associated with excessive production of several angiogenesis regulators which may be found in exhaled breath condensates (EBCs) collected from children with asthma. AIM: To assess the influence of EBC samples of asthmatic children and healthy controls on in vitro cultures of normal human lung microvascular endothelial cells (HLMVEC) and murine endothelial cell line (C-166). Moreover, the proteomic profile of cytokines in EBC samples was analysed. MATERIAL AND METHODS: Breath condensates collected from children with mild asthma (n = 10) and from healthy controls (n = 10) were used for experiments. Colorimetric tetrazolium salt reduction assay was used to evaluate the effect of EBCs on HLMVEC and C-166 cell lines. Furthermore, influence of EBCs on C-166 cell line was assessed using Annexin V-binding assay. The cytokine screening of EBC samples was performed using a proteome microarray system. RESULTS: The EBCs from patients with asthma revealed a weak inhibitory influence on human and murine endothelial cells. Surprisingly, EBCs from healthy children led to cell death, mainly by the induction of apoptosis. There were no statistically significant differences in the cytokine profile between EBC samples from children with asthma and healthy controls. CONCLUSIONS: Our preliminary report shows for the first time that the incubation of EBCs from healthy controls induced apoptosis in endothelial cells. The detailed mechanism responsible for this action remains unknown and requires further research.

Should the Histological Examination Be Used in the Diagnosis of Aneurysms of the Dorsalis Pedis Artery? A Case Report and Review of the Literature.

Aneurysms of the dorsalis pedis artery are rare, and they are not commonly examined histologically. In general, pseudoaneurysms are thought to be more common than true aneurysms of the dorsalis pedis artery. We present a patient with a true aneurysm of the dorsalis pedis artery, which was initially diagnosed as a pseudoaneurysm that had developed because of a blunt trauma of the ankle. However, the intraoperative appearance and histological examination both confirmed a true aneurysm. Our experiences seem to confirm that postoperative histological examination is needed to distinguish pseudoaneurysms from true aneurysms of the dorsalis pedis artery. The treatment of aneurysms of the dorsalis pedis artery is simple and includes resection, which completely relieves the symptoms; few patients need vascular reconstructions.

Amount and distribution of selected biologically active factors in amniotic membrane depends on the part of amnion and mode of childbirth. Can we predict properties of amnion dressing? A proof-of-concept study.

AIM OF THE STUDY: The amniotic membrane is used as a dressing material, e.g. in ocular surgery or treatment of non-healing wounds. Of note, results of previous studies differ significantly, presumably due to the biological properties of amnion. Some authors suggest that these properties may depend on inter-donor variations, as well as the method of delivery. The aim of our study was to analyse the content of selected factors important for tissue regeneration in various areas of amnion samples originating from elective caesarean sections and on-term natural deliveries. MATERIAL AND METHODS: Cervical and placental samples of amniotic membranes originating from physiological deliveries and caesarean sections have been collected with subsequent preparation of amniotic membrane extracts. The screening of amnion samples was performed using a proteome microarray system. RESULTS: In all of the amnion samples high amounts of angiogenin, IGF-binding proteins-1, -2, and -3, serine protease inhibitor E1, and TIMP-1 were detected. Important variations in the content of these factors were observed between physiological delivery and caesarean section-derived membranes, as well as between placental and cervical portions of the same membrane. CONCLUSIONS: Our study has shown that the content of selected growth factors and regulators of ECM turnover in amniotic membrane samples vary between various donations, and that they depend on the region of the membrane or delivery method. This may determine its potential applications in wound treatment and ophthalmologic surgery. However, our observations require further verification in clinical settings.

The MMP-9/TIMP-1 imbalance and the reduced level of TGF-ß in the cervical area of amniotic membrane is a possible risk factor of PROM and premature labor - proof-of-concept study.

OBJECTIVES: To assess the level MMP-9, TIMP-1 and TGF-ß in placental and cervical region of amniotic membranes derived from at-term, pre-term and PROM deliveries. MATERIAL AND METHODS: 14 amniotic membranes have been assessed; the quantitative analysis of MMP-9, TGF-ß and TIMP-1 was assayed using respective Quantikine Immunoassay Kit. RESULTS: The MMP-9 level in PROM samples was similar to the level of MMP-9 in at-term membranes and comparable between the cervical and placental region of these membranes. The concentration of TGF-ß and TIMP-1 was decreased in the cervical area of AM derived from deliveries complicated with PROM. CONCLUSION: The MMP9/TIMP-1 imbalance, as well as the reduced level of TGF-ß may be possible risk factors of pre-term labor and PROM.

Inhaled corticosteroids do not reduce initial high activity of matrix metalloproteinase (MMP)-9 in exhaled breath condensates of children with asthma exacerbation: a proof of concept study.

Inhaled corticosteroids (ICS) are the key component of asthma treatment. However, it is unclear whether they could control the activity and level of matrix metalloproteinase (MMP)-9, which is an important factor in asthma-associated inflammation and airway remodeling. Therefore, the aim of this proof of concept study was to analyze the influence of increased doses of ICS on MMP-9 in exhaled breath condensates (EBC) of patients with allergic asthma exacerbation. Apart from MMP-9, the assessment concerned selected inflammation markers - exhaled nitric oxide (eNO) and cytokines (IL-8 and TNF). The study involved a small group (n = 4) of individuals with asthma exacerbation. The intervention concerned increased doses of ICS with ß-mimetics for 4 weeks. In addition to clinical evaluation, eNO measurements and EBC collections were done before and after 4 weeks of intense ICS treatment. The biochemical assessment of EBC concerned MMP-9, IL-8 and TNF. The data were compared to results of healthy controls (n = 6). The initial levels of eNO, MMP-9 and TNF in EBC were higher in the asthma group than in controls. In all subjects IL-8 levels were below the detection limit. After 4 weeks of ICS treatment in all patients we observed improvement of clinical and laboratory parameters. Interestingly, despite reduction of eNO and TNF, the activity of MMP-9/EBC remained on the initial level. Practical relevance of our results is limited by a small group. Nevertheless, our data suggest that ICS, although sufficient to control symptoms and inflammatory markers, may be ineffective to reduce MMP-9/EBC activity in asthma exacerbation and, possibly, airway remodeling.

Modulation of matrix metalloproteinases MMP-2 and MMP-9 activity by hydrofiber-foam hybrid dressing - relevant support in the treatment of chronic wounds.

Success in chronic wound therapy requires careful selection of appropriate dressing, which enables effective management of wound exudate. According to current knowledge, exudate may contain large quantities of proteases, including matrix metalloproteinases, MMP-2 and MMP-9, which are responsible for delay in wound healing. Therefore, neutralization of MMPs may be beneficial for treatment efficacy. The aim of the study was to test whether AQUACEL Foam, a novel, technologically advanced hydrofiber-foam hybrid dressing (HFHD), may interfere with proteolytic activity of MMPs in vitro. The assessment included in vitro tests of liquid retention and measurement of human recombinant MMP-2 and MMP-9 activity. The MMPs activity was measured before and after their interaction with HFHD, using a fluorescent gelatinase assay kit and Real-Time PCR device. The in vitro tests have shown that the hydrofiber layer of HFHD revealed significant potential to decrease the activity of MMPs in the experimental system. The mentioned modulatory properties of AQUACEL Foam may contribute to a composed mechanism of its beneficial action. Furthermore, our finding may explain clinical effectiveness of HFHD observed in clinical settings.

Amniotic membrane: new concepts for an old dressing.

The amniotic membrane is the innermost layer of fetal membranes that surrounds and protects the embryo. The amniotic epithelial cells are a rich source for biologically active factors known to promote cell proliferation and differentiation. Therefore, the amniotic membrane is considered to be an attractive wound dressing material. Despite a large number of publications reporting anti-inflammatory, bacteriostatic, reepithelializing, and scar-preventing properties of amniotic membrane, not all the molecular mechanisms underlying the beneficial actions of the amniotic membrane dressing have been fully elucidated. This review summarizes current knowledge on the properties of the amniotic membrane and its various clinical applications. It includes an overview of the main biologically active factors that may be responsible for the observed clinical effects of amnion dressings. This issue is briefly discussed in the context of the role of amnion processing and inter- and intradonor variations between amniotic membrane specimens. Finally, future directions for the use of amnion derivatives in wound care are indicated.

Nitric oxide, IL-6 and IL-13 are increased in the exhaled breath condensates of children with allergic rhinitis.

AIM: To evaluate nitric oxide and interleukin (IL)-6, IL-8 and IL-13 in the exhaled breath of children with allergic rhinitis (AR), before and after intranasal allergen exposure. METHODS: A total of 49 children with AR ­ comprising 20 who also had episodic asthma (AR+A) and 29 without asthma (AR) ­ were compared with 34 healthy controls. Nitric oxide concentrations in exhaled air (eNO) and IL-6, IL-8 and IL-13 in exhaled breath condensates (EBC) were measured in winter, outside the natural allergen exposure season, before and after an intranasal allergen challenge. RESULTS: The mean concentrations of eNO, IL-6 and IL-13 were significantly higher in the two AR groups. The concentration of IL-8 was below the assay detection limit in all EBC samples. The intranasal allergen challenge increased IL-13/EBC levels in both AR groups, but did not influence mean concentrations of eNO, IL-6 or IL-8. No challenge-related changes in IL-13/EBC were observed in the allergen-exposed controls or placebo-exposed children. CONCLUSION: Despite local application, the intranasal allergen challenge increased IL-13/EBC concentration in the AR children. As EBC reflects the status of lower airway segments, our observation may support the 'united airways' hypothesis, suggesting a functional link between the upper and lower airways.

Does the Treatment of Pelvic Venous Insufficiency Really Not Influence Lower Limb Venous Disease?

Pelvic venous insufficiency is a common problem in multiparous women. Besides burdensome symptoms, it correlates with the development of venous disease in the lower limbs. Therefore, the sequential treatment of abdominal/pelvic before leg veins could improve treatment effectiveness. The medical records of 243 patients with venous disease who were subjected to sequential treatment were analyzed retrospectively. The symptoms and patient satisfaction were assessed using dedicated questionnaires, both before and after treatment. Clinical effectiveness was verified using a Doppler scan, both before and after treatment. Among 243 analyzed cases, 195 underwent whole treatment; however, 48 women after embolization did not require further intervention. The total-symptom-score change (11.6 vs. 13.0, respectively) and the satisfaction score (1.6 vs. 1.5, respectively) did not differ between groups. After embolization, some patients, besides symptoms improvement, experienced reflux reduction and, hence, might avoid further intervention. A better explanation for this beneficial effect of the sequential/descending approach requires further studies.

May the Number of Pregnancies Predict the Progression and the Outcome of Venous Disease Treatment?

Pregnancy is a well-known risk factor for venous insufficiency. However, even nulliparous women experience venous problems. Therefore, we aimed to assess the possible associations between the number of pregnancies, veins condition and treatment outcome in women with venous disease. The retrospective assessment concerned data of 297 women with diagnosed venous insufficiency. Based on their pregnancy history, the patients' records were divided into: nulliparous women (15.5%), those after 1-2 term pregnancies (57.9%) and those after ≥3 pregnancies (26.6%). The analysis concerned data from the diagnostics of the abdominal/pelvic and leg veins and the treatment results expressed as a symptoms/satisfaction score. Most of the nulliparous women developed venous disease due to mild anatomic abnormalities of the abdominal/pelvic veins. They responded to treatment (mostly unilateral embolization) very well. In the second group, the majority of the combined venous abnormalities responded to treatment with significant improvement, even after embolization alone, although nearly two-thirds still required further leg treatment. The third group was comprised of more advanced cases; nearly 40% of them with recurrence. In order to improve their condition, three-fourths of the cases required sequential treatment in both the pelvic and leg veins compartments. In conclusion, the number of pregnancies is a potent modifying factor in the pathogenesis of venous disease, especially in multiparous women. Together with abnormal venous anatomy, it may determine the treatment outcome.

The Pathogen Isolates in Chronic Wound Infections in Poland.

Chronic wound infection is one of the factors that hinder or prevent its healing. The incidence of infection may vary depending on the type of wound. It is estimated that clinically significant infection in diabetic foot syndrome occurs in up to 30% of patients. Accurate diagnosis of infection features and proper microbiological tests are crucial for introducing of appropriate local and often systemic treatment. The aim of the study was a comparative analysis of the microbiota found in infected chronic wounds in patients from Poland, consulted on an outpatient basis at a wound care center in 2013-2021. The indication for microbiology culture tests was the detection of local signs of infection, and sampling was preceded by appropriate wound debridement. The standard culture technique was a deep-tissue biopsy. Material for the study was collected from 1,199 patients. Overall, 3,917 results of microbiological tests were subjected to retrospective analysis. The paper presents the results in the form of the number of cultured microorganisms and their relative incidence as percentages, considering the division into the types of wounds from which the material was obtained. The most frequently isolated microorganisms in the analyzed group were Staphylococcus aureus (14.3% of this group were MRSA - methicillin-resistant Staphylococcus aureus) and Enterococcus faecalis (2.4% of this group were VRE - vancomycin-resistant Enterococcus). Further analysis of such an extensive database, especially regarding drug susceptibility of isolated microorganisms, seems crucial to elaborate new recommendations for empirical antibacterial treatment of infected chronic wounds.

DPP4 Inhibitors and COVID-19-Holy Grail or Another Dead End?

A novel coronavirus disease, COVID-19, has emerged as a global public health issue. Clinical course of disease significantly correlates with the occurrence of some comorbidities, among them type 2 diabetes. According to recent structural studies the dipeptidyl peptidase 4, a key molecule in the pathophysiology of diabetes, may influence the course of COVID-19. Since DPP4 inhibitors, gliptins, are widely used in diabetes patients, the exact role of DPP4 modulation in SARS-CoV-2 infection, at least in that group, urgently needs to be clarified. In this short review, we discuss this issue with more detail.

Hemodynamic and Radiological Classification of Ovarian Veins System Insufficiency.

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.

Two-Year Follow-Up after Endovenous Closure with Short-Chain Cyanoacrylate versus Laser Ablation in Venous Insufficiency.

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.