Diagnosis and treatment of venous leg ulcers: S2k Guideline of the German Society of Phlebology and Lymphology (DGPL) e.V.

This S2k guideline on venous leg ulcers was created on the initiative and under the leadership of the German Society of Phlebology and Lymphology (DGPL). The guideline group also consisted of representatives from the German Society for Phlebology and Lymphology, German Dermatological Society, German Society for General Medicine, German Society for Angiology, German Society for Vascular Surgery and Vascular Medicine, German Society for Surgery, German Society for Dermatosurgery, German Society for Wound Healing and Wound Treatment, Professional Association of Phlebologists and Lymphologists and Initiative Chronische Wunden. The aim of this guideline is to combine the different approaches and levels of knowledge of the respective professional groups on the basis of consensus, so that a basic concept for the best possible treatment of patients with venous leg ulcers can be provided. A total of 70 specific recommendations were formulated and agreed upon, divided into the subject areas of diagnostics, therapy, prevention of recurrences, and everyday challenges. The guideline thus reflects the current state of scientific knowledge and is intended to be widely used as the best available document for the treatment of patients with venous leg ulcers in everyday clinical practice.

Compression therapy after endovenous laser ablation: Patient compliance and impact on clinical outcome.

OBJECTIVES: This study aimed to investigate the impact of post-interventional compression therapy on clinical outcomes after endovenous laser ablation (EVLA) of incompetent saphenous veins. METHODS: This prospective, controlled, multicenter study in Germany involved 493 varicose vein patients followed-up for 6 months. RESULTS: Compression therapy significantly reduced symptoms compared to no compression (VCSS: 1.4 ± 1.6 vs 2.2 ± 2.2; p = .007). Post-interventional therapy duration of up to 14 days was found to be most effective for improving patient-reported disease severity (p < .001) and higher quality of life (p = .001). Patient compliance was high (82%), and non-compliance was linked to worse disease severity (VCSS 1.4 ± 1.5 vs 2.1 ± 2.3, p = .009). CONCLUSION: In conclusion, post-interventional compression therapy is beneficial by reducing symptoms and improving quality of life. High patient compliance with the therapy is observed, and non-compliance is associated with worse disease severity.

Safety of synchronous prophylactic ablation of the anterior saphenous vein in patients undergoing great saphenous vein thermal ablation- 6 months follow-up data of the SYNCHRONOUS study.

BACKGROUND: The SYNCHRONOUS-study investigates simultaneous ASV-ablation with great saphenous vein (GSV) treatment in endovenous laser ablation (EVLA) for preventing varicose vein recurrence. This sub-study examines complication rates associated with prophylactic ASV-ablation. METHODS: Among 1173 patients with refluxing GSV, 604 underwent GSV-ablation only, and 569 received additional ASV-ablation. Complication rates were compared over 6 months. RESULTS: Approximately 80% of patients were complication-free with minor bruising and dysesthesia being most common complications. After 6 months, additional prophylactic ASV-ablation did not increase the rate of complications compared to GSV-only treatment. CONCLUSION: The 6-months follow-up data suggests that prophylactic ASV-closure, alongside GSV-treatment, is safe, with similar complication rates to GSV-only EVLA.

[Compression therapy for inflammatory dermatoses of the legs]. / Kompressionstherapie bei entzündlichen Dermatosen der Beine.

In addition to venous and lymphatic diseases, there is increasing scientific evidence that inflammatory dermatoses of the legs are also indications for compression therapy. Specifically, diseases such as pyoderma gangrenosum, livedoid vasculopathy, cutaneous vasculitides, necrobiosis lipoidica, psoriasis, or erysipelas are conditions for which adjunctive compression therapy may be used when manifestations occur on the lower extremities. When inflammatory dermatoses are accompanied by edema, compression therapy is not an off-label use. Especially because of the often problematic pain symptoms, compression therapy can be performed with low resting pressures around 20 mmHg, especially in inflammatory dermatoses.In this review article, the current scientific aspects of compression therapy in inflammatory dermatoses of the legs and the corresponding limitations are presented in a differentiated manner.

Cold Plasma Therapy in Chronic Wounds-A Multicenter, Randomized Controlled Clinical Trial (Plasma on Chronic Wounds for Epidermal Regeneration Study): Preliminary Results.

Chronic wounds (CWs) pose a significant health challenge in clinical practice. Standard wound therapy (SWT) is currently considered the gold standard. However, recent evidence suggests that cold plasma therapy (CPT) holds promise for improving CWs. In light of this, the POWER study was conducted as a multicenter, randomized clinical trial to investigate the effect of large-area plasma application compared with SWT in patients with chronic, non-healing arterial or venous wounds on the lower leg. To analyze the interim results, we employed a comprehensive range of statistical tests, including both parametric and non-parametric methods, as well as GLS model regression and an ordinal mixed model. Our findings clearly demonstrate that CPT therapy significantly accelerates wound closure compared with SWT. In fact, complete wound closure was exclusively observed in the CPT group during the intervention period. Additionally, the CPT group required significantly less antibiotic therapy (4%) compared with the SWT group (23%). Furthermore, CPT led to a significant reduction in wound pain and improved quality of life compared with SWT. In conclusion, the study highlights that the combination of CPT and SWT surpasses monotherapy with SWT alone.

Compression therapy in dermatology.

Compression therapy is a conservative therapy that can be used in many patients with dermatological conditions, especially those associated with edema. In addition to its well-established use in venous and lymphatic disorders, there is increasing evidence that compression therapy supports the healing of inflammatory dermatoses. The presence of edema, regardless of its etiology, is an indication for the use of compression therapy. Nowadays, a variety of materials and treatment options are available for compression therapy, each with their own advantages and disadvantages. Often, compression therapy with low resting pressures is sufficient for effective therapy and is better tolerated by patients. The main contraindications to compression therapy are advanced peripheral arterial disease and decompensated heart failure. Individual factors and economic considerations should be taken into account when deciding on compression therapy with the patient. Patient self-management should be encouraged whenever possible. This requires education and support tools.

Undifferentiated pleomorphic sarcoma of the breast with neoplastic fever: case report and genomic characterization.

PURPOSE: Primary breast sarcomas are extraordinary rare, in particular undifferentiated pleomorphic sarcoma (UPS). UPS with neoplastic fever (UPS-NF) of the breast has not been reported yet. Here, we present an extended UPS-NF of the breast including its comprehensive molecular workup. METHODS: A 58-year-old female presented with general malaise, fever spikes, weight loss, and a massively swollen left breast. C-reactive protein and blood leucocytes were significantly increased. However, repeated blood cultures and smears were all sterile. Histopathology of the abscess-forming tumor revealed an undifferentiated malignancy with numerous of tumor giant cells as well as spindle-shaped cells with nuclear pleomorphism and hyperchromasia. Immunohistochemistry demonstrated partial, patchy desmin staining and weak heterogonous neuron-specific enolase immunoreactivity of tumor cells, but a focal staining for Melan-A. RESULTS: Neither common melanoma driver mutations nor an ultraviolet mutational signature was detected by whole genome sequencing. Using FISH and RT-PCR we also excluded translocations characteristic for clear cell sarcoma. Thus, the diagnosis of inflammatory UPS-NF of the breast was considered highly probable. Despite a complete mastectomy, the tumor recurred after only three months. This recurrence was treated with a combination of ipilimumab and nivolumab based on the primary tumor's TPS score for PD-L1 of 30%. After an initial response, however, the tumor was progressive again. CONCLUSION: We describe here the first case of UPS-NF of the breast, which shows great clinical and histopathologic resemblances to previously reported UPS-NF of other anatomic localizations.

[Diagnosis of leg edema]. / Diagnostik von Beinödemen.

Edema of the lower extremities is always associated with a pathological condition that should be treated, especially in patients with chronic wounds. Because the underlying causes of edema can vary greatly and sometimes be complex, clinical and, if necessary, various diagnostic tests should also be performed. Often, a suspected clinical diagnosis can already be made after clinical inspection with testing of Stemmer's and Godet's signs. Sonographic examination should then be performed as the next diagnostic test. Although measurement techniques such as water plethysmography are currently considered gold standard for volume measurements, they are very complex and prone to error, so that they are rarely used in clinical routine today. In summary, it is recommended to perform a clinical examination, if possible in combination with sonography, for edema diagnosis. Especially at the beginning of the decongestion phase, regular circumferential measurements should be performed and documented. This documentation is of high relevance for evaluation of therapeutic success.

A new compression system for treatment of venous leg ulcers: a prospective, single-arm, clinical trial (FREEDOM).

OBJECTIVE: To evaluate the efficacy, tolerability and acceptability of a new multicomponent compression system in one bandage for the local treatment of patients with venous leg ulcers (VLUs). METHOD: This was an international, prospective, non-comparative, clinical trial, conducted in France and Germany. Eligible participants had a VLU with a wound area of 2-20cm2, lasting for a maximum of 24 months. For a period of 6 weeks, patients were treated with a new multicomponent compression system in one bandage which was worn day and night, providing high working pressure and moderate resting pressure (UrgoK1). Clinical assessments, wound measurement and photographs were planned at weeks 1, 2, 4 and 6. The primary endpoint was the relative wound area reduction (RWAR) after 6 weeks of treatment. Secondary endpoints included wound closure rate, oedema resolution, change in patient's health-related quality of life (HRQoL), acceptability, adherence to the compression therapy, local tolerance, and physician's overall satisfaction with the evaluated compression system. RESULTS: A cohort of 52 patients (52% female, mean age 75.4±13.0 years) with VLUs, including oedema in 58% of cases, were recruited from 22 centres. At baseline, 42 patients had already been treated with a different compression system. VLUs had been present for 5.6±4.9 months and had a mean area of 5.7±4.3cm2. After 6 weeks of treatment, a median RWAR of 91% (interquartile range: 39.4; 100.0) was achieved. Wound closure was reported in 35% of patients. A RWAR ≥40% at week 4, predictive of wound healing at 12 weeks, was achieved in 62% of patients. At the final visit, oedema present at baseline was resolved in 57% of patients. Substantial improvements in the HRQoL of the patients were reported with a decrease of the pain/discomfort and anxiety/depression dimensions. Comfort in wearing the evaluated system was reported as 'very good' or 'good' by 79% of patients, resulting in a high patient adherence to compression therapy. Compared to previous compression systems, half of the patients reported more ease in wearing shoes, and greater satisfaction and comfort with this new system. Nine non-serious adverse events related to the device or its procedure occurred in seven patients. At the final visit, the majority of the physicians were 'very satisfied' or 'satisfied' with the new compression system overall. CONCLUSION: The new multicomponent compression system in one bandage has been shown to promote rapid healing of VLUs, reduce oedema, improve HRQoL and to be well tolerated and accepted. It appears to be a viable alternative to existing compression systems.

Einflussfaktoren auf oberflächliche und tiefe Beinvenenthrombosen nach Schaumverödung von Krampfadern.

HINTERGRUND: Bei einer Schaumsklerosierungstherapie von Varizen können als Nebenwirkungen sowohl tiefe (TVT) als auch oberflächliche Beinvenenthrombosen (OVT) auftreten. Noch weitgehend unklar sind die Risikofaktoren, welche die Entstehung einer OVT oder TVT nach Schaumsklerosierung begünstigen. Das Ziel dieser retrospektiven Analyse war, anhand eines größeren Kollektivs von Patienten mit thromboembolischen Komplikationen sowohl patienten- als auch eingriffsbezogene Risikofaktoren für thromboembolische Komplikationen durch eine Schaumsklerosierung herauszuarbeiten. PATIENTEN UND METHODIK: Insgesamt wurden 170 Patienten untersucht, die eine Schaumsklerosierung erhielten. Vor dem Stichtag 17. März 2020 wurden die letzten 85 Patienten mit thromboembolischen Komplikationen als Studiengruppe A und die letzten 85 Patienten ohne thromboembolische Komplikationen als Kontrollgruppe B nach Sklerosierung mit aufgeschäumtem Sklerosierungsmittel erfasst und verglichen. ERGEBNISSE: Patienten mit thromboembolischen Komplikationen hatten häufiger eine Thrombophilie (11/85 vs. 3/85). Die mittleren BMI-Werte waren in Gruppe A (25,9 ± 5,1) signifikant niedriger als in Gruppe B (28,0 ± 7,2) (P = 0,034). Thromboembolische Komplikationen zeigen sich nach Schaumsklerosierung eher am Unterschenkel (61/105) als am Oberschenkel (1/13) (P < 0,001) dabei häufiger nach dorsaler als nach ventraler Schaumsklerosierung (39 von 47 vs. 5 von 40, P < 0,001). Von den 39 thromboembolischen Komplikationen am dorsalen Unterschenkel waren 23 Muskelvenenthrombosen. SCHLUSSFOLGERUNG: Das Risiko für Muskelvenenthrombosen nach Schaumsklerosierung ist vor allem bei schlanken Patienten, welche am dorsalen Unterschenkel sklerosiert werden, erhöht.

Factors influencing superficial and deep vein thrombosis after foam sclerotherapy in varicose veins.

BACKGROUND: Side effects of foam sclerotherapy for varicose veins can include both deep (DVT) and superficial leg vein thrombosis (SVT). The risk factors that favor the development of SVT or DVT after foam sclerotherapy are still largely unclear. The aim of our retrospective analysis was to use a larger group of patients with thromboembolic complications to identify both patient-related and procedure-related risk factors for thromboembolic complications from foam sclerotherapy. PATIENTS AND METHODS: A total of 170 patients who received foam sclerotherapy were examined. With reference to a cut-off date, March 17th, 2020, the 85 most recent patients with thromboembolic complications (study group A) were included and compared to the most recent 85 patients without thromboembolic complications (control group B), after sclerotherapy with foamed sclerosant. RESULTS: Patients with a thromboembolic complication were more likely to have thrombophilia (11/85 vs. 3/85). The mean BMI values in group A (25.9 ± 5.1) were significantly lower than in group B (28.0 ± 7.2) (P = 0.034). Thromboembolic complications were more likely to appear after foam sclerotherapy on the lower leg (61/105) than on the thigh (1/13) (P < 0.001), particularly after dorsal than after ventral foam sclerotherapy (39 of 47 vs. 5 of 40, P < 0.001). Of the 39 thromboembolic complications on the dorsal lower leg, 23 were muscle vein thromboses. CONCLUSION: The risk of muscle vein thrombosis after foam sclerotherapy is especially increased in slender patients with sclerosed, dorsal lower legs.

[Medical compression stockings for chronic venous diseases and lymphedema : Scientific evidence and results of a patient survey on quality of care]. / Medizinische Kompressionsstrümpfe bei chronischen venösen Erkrankungen und Lymphödem : Wissenschaftliche Evidenz und Ergebnisse einer Patient*innen-Befragung zur Versorgungsqualität.

BACKGROUND AND AIMS: Medical compression stockings (MCS) are indicated for chronic venous insufficiency (CVI) of all stages and are an indispensable component in lymphedema therapy. In all, 8% of the German population has been prescribed MCS by a physician-more women than men (12% vs. 5%), and especially persons aged 60 years and older (17%). Patient adherence is relevant for successful treatment with MCS. We examined MCS use from the patient's perspective. PATIENTS AND METHODS: This study examined the quality of care through structured interviews with 414 representative users in 2019. Findings are discussed taking into consideration scientific evidence on the efficacy of MCS. RESULTS: Venous conditions are the most common reason for prescription (44%), followed by lymphedema (22%) or multiple indications (27%). Patients generally wear MCS daily and on average 11 h/day. In all, 89% of patients were satisfied or very satisfied with MCS, whereby efficacy was dependent on the indication. This reflects the extensive scientific evidence on the clinical efficacy of MCS. An important factor for patient adherence is physician training and education. CONCLUSION: MCS are well accepted by patients. When prescribing them, practical aspects such as donning and doffing, recommended wearing time and frequency, and the mechanism of action of MCS should be clearly communicated.

Impact of a synchronous prophylactic treatment of the anterior accessory saphenous vein on the recurrent varicose vein rate in patients undergoing thermal ablation of an insufficient great saphenous vein (SYNCHRONOUS-Study): study protocol for a prospective, multicentre, controlled observational study.

INTRODUCTION: To date, there are no prospective studies evaluating the prevention of recurrent veins by the simultaneous treatment of a sufficient anterior accessory saphenous vein (AASV) in patients undergoing endovenous laser ablation (EVLA) of an insufficient great saphenous vein (GSV). This study will provide important information about the impact of the AASV on the development of recurrent veins after EVLA of the GSV. Additionally, it will be clarified whether patients benefit from a preventive ablation of a sufficient AASV. METHODS AND ANALYSIS: This is a multicentre, prospective, controlled, exploratory clinical study in 1150 patients with a medical indication for EVLA of a refluxing great saphenous vein. Patients will be enrolled into two study groups: in half of the patients EVLA will be performed on the insufficient GSV only. In the other half of the patients EVLA will be performed on the insufficient GSV and additionally on the sufficient AASV. Within seven study visits, patients will be followed-up over a time period of 5 years. Primary study endpoint is the recurrence rate; secondary endpoints include inter alia, complication rate, postoperative pain intensity, quality of life and patient satisfaction. ETHICS AND DISSEMINATION: Before initiation of the study, the protocol was presented and approved by the independent ethics committee of the medical faculty of the University of Heidelberg (Ethics approval number S-596/2018). This study was prospectively registered at the German Clinical Trial Register (https://www.germanctr.de/). Research findings will be disseminated in a peer-reviewed journal and at relevant conferences. TRIAL REGISTRATION NUMBER: German Clinical Trial Registry (DRKS00015486).

[Superficial venous thrombosis, varicose veins, and chronic venous insufficiency: an update for clinical practice]. / Oberflächliche Venenthrombose, Varikose und chronische Veneninsuffizienz ­ Update für die Praxis.

BACKGROUND: Venous disorders affect a large proportion of the German population (varicose veins 13.3%, chronic venous insufficiency 40.8%). OBJECTIVES: Based on current literature, a practically oriented update on superficial venous thrombosis, varicosis, and chronic venous insufficiency is provided. RESULTS AND CONCLUSION: Superficial vein thrombosis of the legs requires comprehensive duplex ultrasonography of the superficial and deep leg veins. Only superficial vein thrombosis less than 5 cm in length and more than 3 cm from the saphenofemoral or saphenopopliteal junction can be treated conservatively with compression, cooling, and relative immobilization. Superficial vein thrombosis greater than 5 cm in length with more than 3 cm distance to the deep venous system is treated pharmacologically with fondaparinux for 45 days (approved for 30-45 days). If the surface thrombus reaches the saphenofemoral or saphenopopliteal junction at a distance of less than 3 cm, therapy analogous to deep vein thrombosis is required for 3 months. The most effective therapy for varicose veins is invasive removal. In this regard, endovenous thermal ablation has become particularly important in recent years, given that its effectiveness is of a similar order of magnitude to that of crossectomy and stripping surgery, but the complication rates are significantly lower. Invasive removal of varicose veins not only improves patients' quality of life, but also significantly reduces the risk of deep vein thrombosis. Recent epidemiological data demonstrate an increased risk of cardiovascular disease in patients with chronic venous insufficiency. There is preliminary evidence that this risk of cardiovascular disease in varicose vein patients can be lowered by varicose vein therapy.

Antibody-Negative Paraneoplastic Autoimmune Multiorgan Syndrome (PAMS) in a Patient with Follicular Lymphoma Accompanied by an Excess of Peripheral Blood CD8+ Lymphocytes.

Paraneoplastic autoimmune multiorgan syndrome (PAMS) is a life-threatening autoimmune disease associated with malignancies. Here, we present a patient initially misdiagnosed with "chronic" Stevens-Johnson syndrome. Over a year later, the patient was diagnosed with stage IV follicular lymphoma and treated with an anti-CD20 antibody. At this time, his skin condition had significantly worsened, with erythroderma and massive mucosal involvement, including in the mouth, nose, eyes, and genital region. Histopathology revealed lichenoid infiltrates with interface dermatitis, dyskeratoses, necrotic keratinocytes, and a dense CD8+ infiltrate with strong epidermotropism. Direct and indirect immunofluorescence tests for autoantibodies were negative. Remarkably, we retrospectively discovered a chronic increase in peripheral CD8+ lymphocytes, persisting for over a year. Consequently, the patient was diagnosed with antibody-negative PAMS. Three weeks later, he succumbed to respiratory failure. This dramatic case highlights the challenges in diagnosing PAMS, particularly in cases where immunofluorescence assays are negative. Importantly, we observed, for the first time, a chronic excess of CD8+ peripheral blood lymphocytes, associated with PAMS, consistent with the systemic, autoreactive T-cell-driven processes that characterize this condition.

Allogeneic ABCB5+ mesenchymal stem cells for treatment-refractory chronic venous ulcers: a phase I/IIa clinical trial.

A significant number of chronic venous ulcers (CVUs) fail to heal despite of guideline-conform standard of care. Skin-derived ABCB5+ mesenchymal stem cells (MSCs) can dampen the sustained IL-1ß-driven inflammation present in chronic wounds. Based on their wound healing-facilitating effects in a mouse CVU model and an autologous first-in-human study, ABCB5+ MSCs have emerged as a potential candidate for cell-based advanced therapy of non-healing CVUs. In the present interventional, multicenter, single-arm, phase I/IIa clinical trial, subjects whose CVU had emerged as standard therapy-resistant received one or two topical applications of 1×106 allogeneic ABCB5+ MSCs/cm2 wound area in addition to standard treatment. Out of 83 treatment-emergent adverse events, only three were judged related to the cell product; they were mild or moderate and recovered without sequelae. Wound size markedly decreased from baseline to week 12, resulting in a median wound size reduction of 76% (full analysis set, N=31), 78% (per-protocol set, N=27) and 87% (subset of responders; n=21). In conclusion, the study treatment was well tolerated and safe. The treatment elicited a profound wound size reduction within 12 weeks, identifying ABCB5+ MSCs as a potential candidate for adjunctive therapy of otherwise incurable CVUs. These results justify the conduct of a larger, randomized, controlled trial to confirm clinical efficacy.

Cellular senescence at the saphenofemoral junction in patients with healthy, primary varicose and recurrent varicose veins - A pilot study.

OBJECTIVES: Cellular senescence could play a role in the development of venous disease. Superficial venous reflux at the saphenofemoral junction is a common finding in patients with primary varicose veins. Furthermore, reflux in this essential area is associated with higher clinical stages of the disease and recurrent varicose veins. Therefore, this pilot study aimed to investigate cellular senescence in the immediate area of the saphenofemoral junction in patients with healthy veins, primary varicose veins and additionally in patients with recurrent varicose veins due to a left venous stump. METHODS: We analyzed vein specimens of the great saphenous vein immediately at the saphenofemoral junction. Healthy veins were collected from patients who underwent arterial bypass reconstructions. Samples with superficial venous reflux derived from patients who received high ligation and stripping or redo-surgery at the groin, respectively. Sections were stained for p53, p21, and p16 as markers for cellular senescence and Ki67 as a proliferation marker. RESULTS: A total of 30 samples were examined (10 healthy, 10 primary varicose, and 10 recurrent varicose veins). We detected 2.10% p53+ nuclei in the healthy vein group, 3.12% in the primary varicose vein group and 1.53% in the recurrent varicose vein group, respectively. These differences were statistically significant (p = 0.021). In the healthy vein group, we found 0.43% p16+ nuclei. In the primary varicose vein group, we found 0.34% p16+ nuclei, and in the recurrent varicose vein group, we found 0.74% p16+ nuclei. At the p < 0.05 level, the three groups tended to be significant without reaching statistical significance (p = 0.085). There was no difference in respect of p21 and Ki67. CONCLUSION: We found significantly higher expression rates of p53 in primary varicose veins at the saphenofemoral junction than in healthy veins. p16 expression tended to be increased in the recurrent varicose vein group. These preliminary findings indicate that cellular senescence may have an impact in the development of varicose veins or recurrence. Further studies addressing this issue are necessary.