Plasma Soluble Glycoprotein VI, Platelet Function, Bleeding, and Ischemic Events in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND AND AIMS: Glycoprotein VI (GPVI) is the major platelet-specific collagen receptor. GPVI shedding with generation of soluble GPVI (sGPVI) is an endogenous feedback mechanism preventing platelet overstimulation. sGPVI has not been investigated in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI), especially regarding its potential value as a predictor of ischemic and bleeding risk. METHODS: Baseline plasma sGPVI levels were available in 318 patients with CCS undergoing PCI. Platelet function was assessed by measuring both adenosine diphosphate (ADP) and collagen-induced platelet aggregation. Co-primary endpoints were a composite of death or myocardial injury at 48 hours after PCI, and Bleeding Academic Research Consortium (BARC) type 1 to 5 bleeding at 30 days. RESULTS: There was no significant correlation between sGPVI and platelet function at baseline or at 48 hours after PCI and loading with antiplatelet drugs. Baseline plasma sGPVI levels were not associated with the ischemic risk: the incidence of the ischemic endpoint was 25.0% in the lower, 22.9% in the middle, and 26.7% in the upper sGPVI tertile (p = 0.82). There was a significant nonlinear relationship between sGPVI and the risk of bleeding: the incidence of the bleeding endpoint was 11.8% in the lower, 12.6% in the middle, and 26.4% in the upper sGPVI tertile (p = 0.006). CONCLUSION: In patients with CCS undergoing PCI, plasma levels of sGPVI did not correlate with ADP- or collagen-induced platelet aggregation. Patients with higher baseline levels of sGPVI may carry an increased risk of bleeding at 30 days after PCI but no excess risk of ischemic events.

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to Estimated Glomerular Filtration Rate.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs). BACKGROUND: The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined. METHODS: Patients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m2), intermediate eGFR (≥60 and <90 mL/min/1.73 m2), and high eGFR (≥90 mL/min/1.73 m2). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year. RESULTS: Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding. CONCLUSIONS: These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800).

Efficacy and safety of ticagrelor versus prasugrel in smokers and nonsmokers with acute coronary syndromes.

BACKGROUND: The efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with acute coronary syndromes (ACS) are not known. We assessed the efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with ACS undergoing invasive management. METHODS: This pre-specified analysis of the ISAR-REACT 5 trial included 1349 smokers and 2652 nonsmokers randomized to receive ticagrelor or prasugrel. The primary endpoint was the incidence of death, myocardial infarction, or stroke; the secondary endpoint was the incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding (both endpoints assessed at 12 months). RESULTS: There was no significant treatment arm-by-smoking status interaction regarding the efficacy outcome. The primary endpoint occurred in 47 patients (7.0%) in the ticagrelor group and 41 patients (6.2%) in the prasugrel group in smokers (hazard ratio [HR] = 1.15; 95% confidence interval [CI] 0.76-1.75; P = 0.510) and in 133 patients (10.2%) in the ticagrelor group and 94 patients (7.2%) in the prasugrel group in nonsmokers (HR = 1.44 [1.10-1.87]; P = 0.007; P for interaction = 0.378). The secondary endpoint occurred in 27 patients (4.6%) in the ticagrelor group and 33 patients (5.6%) in the prasugrel group in smokers (HR = 0.81 [0.49-1.35]; P = 0.412) and in 66 patients (6.0%) in the ticagrelor group and 46 patients (4.4%) in the prasugrel group in nonsmokers (HR = 1.38 [0.94-2.01]; P = 0.097). CONCLUSIONS: In patients with ACS undergoing an invasive management strategy, the smoking status did not significantly interact with the relative treatment effect of ticagrelor vs. prasugrel. CLINICAL TRIAL REGISTRATION: NCT01944800.

Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial.

Importance: The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant. Objective: To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI. Design, Setting, and Participants: A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI). Interventions: Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy. Main Outcomes and Measures: The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days. Results: Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5'-diphosphate-induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36). Conclusions and Relevance: Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms. Trial Registration: ClinicalTrials.gov Identifier: NCT03312855.

Ticagrelor or Prasugrel in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI). OBJECTIVES: This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management. METHODS: This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5. RESULTS: The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month. CONCLUSIONS: In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800).

Ticagrelor or Prasugrel in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. RESULTS: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

External valvuloplasty of the saphenofemoral junction in insufficient great saphenous veins - six weeks results of a prospective multicentre trial.

Background: Varicosis of the great saphenous vein (GSV) is a common disease. Most of the therapeutic concepts attempt to remove or destroy the truncal vein. However, the absence of the GSV could be harmful for further treatments of artherosclerotic disease as the GSV is often used as bypass graft in lower extremity or coronary artery revascularisations. External valvuloplasty (EV) is one of the vein-sparing treatment options. The aim of this clinical study was to describe the outcome, safety and complications of this procedure in a prospective multicentre trial. Patients and methods: The function of the terminal and preterminal valve was restored by external valvuloplasty. Furthermore, multiple phlebectomies of tributaries were performed. Patients were reinvestigated six weeks after surgery. Primary endpoint was the function of the external valvuloplasty measured by diameter of the GSV and the prevalence of reflux in the GSV. The eligibility of the vein as a potential bypass graft was noticed. CEAP class and VCSS scores were analysed. Results: A total of 359 patients were included in the study. After six weeks 297 patients could be reinvestigated. The function of the external valvuloplasty was sufficient in 284 patients (95.6%). Treatment failed in 8 patients (2.6%) due to an occlusion or junctional reflux despite valvuloplasty. The GSV was estimated as suitable as a bypass graft in 261 patients (87.8%). Reflux at the saphenofemoral junction was significantly reduced after treatment and the diameter of the GSV near the saphenofemoral junction significantly decreased from 4.4 mm to 3.8 mm (p < 0.05). The VCSS was significantly reduced from 4.6 preoperatively to 2.6 postoperatively. Conclusions: External repair of the great saphenous vein can reduce venous symptoms and may preserve the great saphenous vein as a bypass graft. Nevertheless, this treatment option is only suitable for a limited number of patients.

Surgical thrombectomy for iliofemoral deep vein thrombosis: Patient outcomes at 8.5 years.

INTRODUCTION: Deep vein thrombosis (DVT) is a frequent burden and a post-thrombotic syndrome (PTS) can be a serious long-term consequence. Iliofemoral DVT should be associated with severe forms of PTS. Therefore an early thrombus removal has been recommended in specific conditions. The aim of this study was to find out both, the long-term results after surgical thrombectomy of iliofemoral DVT in respect of the development of PTS as well as the venous hemodynamics after surgery concerning venous reflux and venous obstruction. METHODS: Sixty-seven patients who underwent surgical thrombectomy between the years 2000 and 2014 were included in this study; iliofemoral DVT was present in 52 of these patients. 35 patients could be reinvestigated after a mean follow-up of 8.5 years. CEAP (Clinical-Etiological-Anatomical-Pathophysiological) and Villalta scores were recorded in order to describe and assess PTS. Follow-up examinations included a detailed duplex mapping. Venous hemodynamics were measured by digital photoplethysmography and venous occlusion plethysmography. RESULTS: The primary patency rate of the iliofemoral segment was 88% after 8.5 years. 48% of all patients showed reflux in deep vein segments. Mild or moderate PTS occurred in 57% of all patients. Notably, there was no patient with an active ulcer or severe PTS. The mean venous outflow volume of all patients in the treated legs was 66.1 ml/100ml/min and significantly less than in the controlled contralateral non-treated legs (p<0.05). The mean venous refilling time was 16.3 seconds, while the mean value of the non-treated contralateral legs was 25.6 seconds and therefore significantly higher (p<0.05). CONCLUSION: Even though venous hemodynamics are significantly inferior in the treated legs, this study demonstrates excellent patency rates and good clinical outcome after surgical thrombectomy of iliofemoral veins.

Multimodal approach of venous recanalization in patients with a critical limb ischemia due to phlegmasia cerulea dolens: A case series of 17 patients in a single center.

OBJECTIVES: Advanced phlegmasia cerulea dolens can be a hazardous complication of a deep vein thrombosis and rapid recanalization of the deep venous system is the most important factor. METHOD: We describe the outcome of 17 patients with critical limb ischemia due to an advanced phlegmasia cerulea dolens. Venous thrombectomy was performed by a standardized operating procedure. RESULTS: Venous recanalization was successful in all patients. An additional fasciotomy was not necessary. There were five patients with an underlying malignancy and eight patients with a simultaneous pulmonary embolism. We had one amputation of a forefoot and one death within 30 days representing a 30-day mortality and an amputation rate of 6%. CONCLUSIONS: Early recanalization and recovery of the venous outflow is mandatory for success. A multimodal therapeutic approach of high urgency surgical thrombectomy in combination with endovenous strategies could be a successful treatment option for advanced phlegmasia cerulea dolens.

Randomized Comparison of Intensified and Standard P2Y12-Receptor-Inhibition Before Elective Percutaneous Coronary Intervention: The SASSICAIA Trial.

BACKGROUND: Even among biomarker-negative patients undergoing elective percutaneous coronary intervention (PCI), periprocedural thrombotic and bleeding complications can lead to increased morbidity and mortality. Whether stronger platelet inhibition by an intensified oral loading strategy (ILS) before PCI impacts on outcomes among these patients in contemporary practice remains unclear. METHODS: This multicenter, randomized, assessor-blinded trial tested the hypothesis that in elective PCI prasugrel 60 mg (ILS) is superior to standard loading strategy with clopidogrel 600 mg regarding a composite primary end point of all-cause death, any myocardial infarction, definite/probable stent thrombosis, stroke, or urgent vessel revascularization. After PCI, all patients were on clopidogrel 75 mg/day and aspirin. The trial was terminated prematurely because of slower-than-expected recruitment and funding discontinuation. RESULTS: Of 781 patients included in the final analysis, 382 were assigned to ILS and 399 to standard loading strategy. At 30 days, the primary end point occurred in 66 patients (17.3%) assigned to ILS and 74 patients (18.6%) assigned to standard loading strategy (odds ratio, 0.92 [95% CI, 0.63-1.32]; P=0.64). Any myocardial infarction and Bleeding Academic Research Consortium ≥2 bleeding rates were similar among ILS and standard loading strategy groups 16.2% versus 17.5%, odds ratio, 0.91 (95% CI, 0.62-1.32), P=0.62 and 4.2% versus 4.8%, odds ratio 0.87 (95% CI, 0.44-1.73), P=0.70, respectively. CONCLUSIONS: In biomarker-negative stable and unstable angina patients undergoing elective PCI, the trial did not find a conclusive difference in efficacy or safety. This observation should be interpreted in the context of wide CIs and premature termination of the trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02548611.

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Age-dependent impact of the SYNTAX-score on longer-term mortality after percutaneous coronary intervention in an all-comer population.

BACKGROUND: The Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX)-score is a validated tool for risk stratification and revascularization strategy selection in patients with complex coronary artery disease. The aim of this study was to analyse its age-related prognostic value. METHODS: SYNTAX-score was calculated in 1331 all-comer patients undergoing percutaneous coronary intervention (PCI): 463 patients ≥ 75 years and 868 patients < 75 years. Outcomes of interest were all-cause mortality at one and two years. RESULTS: A significant interaction of age and SYNTAX-score for mortality was observed at two-year (P interaction = 0.019) but not at one-year follow-up (P interaction = 0.594). In multivariable analysis, SYNTAX-score independently predicted 1-year mortality in both age groups (< 75 years, hazard ratio (HR): 1.43, 95% confidence intervals (CI): 1.03-2.00, P = 0.034; and ≥ 75 years, HR: 1.37, 95% CI: 1.01-1.85, P = 0.042), but only two-year mortality among younger patients (< 75 years, HR: 1.33, 95% CI: 1.01-1.76, P = 0.041; and ≥ 75 years, HR: 1.11, 95% CI: 0.87-1.41, P = 0.394). SYNTAX-score tertiles were useful to stratify 1-year mortality in both, patients < 75 years (SYNTAX-score < 9, 3.8%; 9-20, 5.3%; ≥ 20, 10.3%; P = 0.004) and ≥ 75 years (SYNTAX-score < 11, 5.7%; 11-22.5, 16.1%; ≥ 22.5, 18.7%; P = 0.003), but two-year mortality only among patients < 75 years (SYNTAX-score < 9, 6.5%; 9-20, 7.6%; ≥ 20, 15%; P < 0.001) and not among ≥ 75 years old patients (SYNTAX-score < 11, 19.4%; 11-22.5, 26.3%; ≥ 22.5, 27.9%; P = 0.138). CONCLUSIONS: Age modifies the impact of the SYNTAX-score on longer-term mortality after PCI. Among patients < 75 years, the SYNTAX-score independently predicts the risk of death at one and two years after PCI, while among patients ≥ 75 years its predictive role is limited to the first year after PCI. Further studies are needed to evaluate the value of SYNTAX-score for selecting the most appropriate revascularization strategy among elderly patients.

S1 guidelines: Lipedema.

The present, revised guidelines on lipedema were developed under the auspices of and funded by the German Society of Phlebology (DGP). The recommendations are based on a systematic literature search and the consensus of eight medical societies and working groups. The guidelines contain recommendations with respect to diagnosis and management of lipedema. The diagnosis is established on the basis of medical history and clinical findings. Characteristically, there is a localized, symmetrical increase in subcutaneous adipose tissue in arms and legs that is in marked disproportion to the trunk. Other findings include edema, easy bruising, and increased tenderness. Further diagnostic tests are usually reserved for special cases that require additional workup. Lipedema is a chronic, progressive disorder marked by the individual variability and unpredictability of its clinical course. Treatment consists of four therapeutic mainstays that should be combined as necessary and address current clinical symptoms: complex physical therapy (manual lymphatic drainage, compression therapy, exercise therapy, and skin care), liposuction and plastic surgery, diet, and physical activity, as well as psychotherapy if necessary. Surgical procedures are indicated if - despite thorough conservative treatment - symptoms persist, or if there is progression of clinical findings and/or symptoms. If present, morbid obesity should be therapeutically addressed prior to liposuction.

Squamous cell carcinomas in chronic venous leg ulcers. Data of the German Marjolin Registry and review.

BACKGROUND: Secondary squamous cell carcinoma (SCC) is a rare complication of chronic venous leg ulcers. So far, little is known about its pathophysiology and clinical behavior. Initiated by the working group "Wound Healing" (AGW) of the German Society of Dermatology (DDG), it is the objective of the current Marjolin registry to collect cases of SCC arising in venous ulcers, in order to evaluate diagnostic characteristics. PATIENTS AND METHODS: All members of the AGW received questionnaires inquiring about basic patient data, ulcer characteristics, and therapy conducted. RESULTS: From 2010 to 2013, 30 patients (20 women, 10 men) from six tertiary wound care centers were registered. Mean age was 76.17 years. The average duration of venous leg ulcers prior to SCC diagnosis was 15.93 years. Suspicious wound characteristics primarily included: pain (n = 3), therapy resistance (n = 27), and fetor (n = 12) as well as clinical appearance (n = 10) with atypical morphology, nodular wound bed, and hypergranulation. CONCLUSIONS: Atypical morphology or changes in appearance as well as therapy resistance despite optimal care (6-12 weeks) should prompt physicians to take spindle-shaped, if necessary multiple and serial, biopsies. Primary risk factors for malignant transformation include patient age and ulcer duration.