Development of a localization-based algorithm for the prediction of leg ulcer etiology.

BACKGROUND: Diagnostic work-up of leg ulcers is time- and cost-intensive. This study aimed at evaluating ulcer location as a diagnostic criterium and providing a diagnostic algorithm to facilitate differential diagnosis. PATIENTS AND METHODS: The study consisted of 277 patients with lower leg ulcers. The following five groups were defined: Venous leg ulcer, arterial ulcers, mixed ulcer, arteriolosclerosis, and vasculitis. Using computational surface rendering, predilection sites of different ulcer types were evaluated. The results were integrated in a multinomial logistic regression model to calculate the likelihood of a specific diagnosis depending on location, age, bilateral involvement, and ulcer count. Additionally, neural network image analysis was performed. RESULTS: The majority of venous ulcers extended to the medial malleolar region. Arterial ulcers were most frequently located on the dorsal aspect of the forefoot. Arteriolosclerotic ulcers were distinctly localized at the middle third of the lower leg. Vasculitic ulcers appeared to be randomly distributed and were markedly smaller, multilocular and bilateral. The multinomial logistic regression model showed an overall satisfactory performance with an estimated accuracy of 0.68 on unseen data. CONCLUSIONS: The presented algorithm based on ulcer location may serve as a basic tool to narrow down potential diagnoses and guide further diagnostic work-up.

Comparative analysis of endovenous laser ablation versus ultrasound-guided foam sclerotherapy for the treatment of venous leg ulcers.

Endovenous thermal and non-thermal therapeutic approaches have become standard of care for the treatment of venous insufficiency. However, comparative studies on its use in the population of venous leg ulcer patients are scarce. The present study aimed at a comparison of the efficacy of endovenous laser ablation (EVLA) and ultrasound-guided foam sclerotherapy (UGFS) for the treatment of venous leg ulcers (VUs). We retrospectively analyzed patient records of 68 patients with active VUs (C6 of the CEAP-classification), who underwent EVLA (n = 33) or UGFS (n = 35) between January 2001 and January 2021. In 68 patients, 97 venous segments (GSV: 43, SSV: 17, NSV: 37) were treated. Ulcer surface area at initial presentation did not differ significantly between both treatment groups (EVLA: 7.7 ± 10.7 vs. UGFS: 8.5 ± 16.3 cm2 ; p = 0.73). No significant difference regarding patient characteristics was found, with the exception of age, as patients receiving UGFS treatment were significantly older (EVLA: 61 ± 17 vs. UGFS: 70 ± 14 years; p = 0.018). The rate of ulcer resolution was not significantly different between EVLA and UGFS groups (97.0% vs. 85.7%; p = 0.20). Also, the mean time to complete ulcer healing after endovenous intervention was comparable (EVLA: 59 ± 37 vs. UGFS: 63 ± 41 days; p = 0.68). However, the relapse rate was significantly higher for UGFS than for EVLA treated patients (31.4% vs. 3.0%; p = 0.002). Taken together, rates of ulcer resolution and ulcer healing time after endovenous intervention were comparable between both treatment modalities. Nevertheless, a significantly higher relapse rate was observed in UGFS treated patients.

Differentiating Arteriolosclerotic Ulcers of Martorell from Other Types of Leg Ulcers Based on Vascular Histomorphology.

Clinical differential diagnosis of arteriolosclerotic ulcers of Martorell is challenging due to the lack of clearly affirmative instrument-based diagnostic criteria. The aim of this study was to develop vascular histomorphological diagnostic criteria differentiating Martorell ulcers from other types of leg ulcers. The histomorphology of patients diagnosed with arteriolosclerotic ulcers of Martorell (n = 67) was compared with that of patients with venous leg ulcers, necrotizing leukocytoclastic vasculitis, pyoderma gangrenosum, and non-ulcerative controls (n = 15 each). In a multivariable logistic regression model, the rates of arteriolar calcification (odds ratio (OR) 42.71, 95% confidence interval (CI) 7.43-443.96, p < 0.001) and subendothelial hyalinosis (OR 29.28, 95% CI 4.88-278.21, p <0.001) were significantly higher in arteriolosclerotic ulcers of Martorell. Arteriolar cellularity was significantly lower in Martorell ulcers than in controls (OR 0.003, 95 CI < 0.001-0.97, p = 0.05). However, the wall-to-lumen ratio was similar in all ulcers (OR 0.975, 95% CI 0.598-2.04, p =0.929). Based on the Youden index, a wall cellularity of < 0.24 cells/100 µm2 was determined as the optimum cut-off point (sensitivity 0.955, specificity 0.944). Thus, arteriolar calcification, subendothelial hyalinosis, and arteriolar cellularity revealed high discriminatory power for arteriolosclerotic ulcers of Martorell.

Multidisciplinary long-term care and modern surgical treatment of congenital melanocytic nevi - recommendations by the CMN surgery network.

In recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German-speaking countries with extensive experience in long-term care and surgical treatment of children and adults with CMN (CMN surgery network, "Netzwerk Nävuschirurgie", NNC). The authors address aspects such as the indication for treatment as well as treatment planning and implementation under these new premises. Adequate counseling of parents on conservative and/or surgical management requires an interdisciplinary exchange among physicians and individualized planning of the intervention, which frequently involves a multi-stage procedure. Today, the long-term aesthetic outcome is at the center of any therapeutic endeavor, whereas melanoma prevention plays only a minor role. The premise of "removal at any cost" no longer holds. Potential treatment-related adverse effects (hospitalization, wound healing disorders, and others) must be carefully weighed against the prospects of a beneficial outcome. In this context, the use of dermabrasion in particular must be critically evaluated. At a meeting of the NNC in September 2018, its members agreed on a consensus-based position on dermabrasion, stating that the procedure frequently leads to impaired wound healing and cosmetically unfavorable or hypertrophic scarring. Moreover, dermabrasion is considered to be commonly associated with considerable repigmentation that usually occurs a number of years after the procedure. In addition, the NNC members saw no benefit in terms of melanoma prevention. In the future, physicians should therefore thoroughly caution about the potential risks and often limited cosmetic benefits of dermabrasion.

Opioid use after propofol or sevoflurane anesthesia: a randomized trial.

BACKGROUND: The intravenous anesthetic propofol is a gamma-aminobutyric acid A receptor agonist. Propofol promotes analgesia by depressing nociceptive transmission in peripheral neurons, antagonizing N-methyl-D-aspartate receptors, and activating gamma-aminobutyric acid A receptors in dorsal root ganglion receptor cells. Nevertheless, it remains unclear whether intraoperative propofol causes clinically meaningful postoperative analgesia. We therefore tested the hypothesis that patients anesthetized with sevoflurane require a greater quantity of postoperative opioids (from the end of surgery until the next postoperative morning) than those anesthetized with propofol. METHODS: With Institutional Review Board and EudraCT Number approval (2009-011038-82) and patients' informed consent, ninety patients scheduled for open vein stripping were randomized to either sevoflurane or propofol anesthesia at the Medical University of Vienna General Hospital and the Danube Hospital, the largest regional hospital in Vienna. Pain was treated with bolus piritramide and patient-controlled morphine hydrochloride. The primary outcome was total opioid use from the end of surgery until the first postoperative morning. For the initial four postoperative hours and on the first postoperative morning, a blinded investigator recorded pain scores on an 11-point Likert verbal response scale. RESULTS: The median [interquartile range] morphine sulfate equivalents were 9.8 [4-19] mg in the sevoflurane group and 10 [6-20] mg in the propofol group. Sevoflurane was not superior to propofol on postoperative opioid consumption, giving a ratio of means of 0.91 (95% interim-adjusted confidence interval [CI], 0.33 to 2.45; P = 0.74). Additionally, no difference in pain scores was found over time between the two groups, with a mean difference on an 11-point scale of 0.20 (95% interim-adjusted CI, -0.36 to 0.73; P = 0.31). CONCLUSION: Intraoperative sevoflurane did not reduce postoperative analgesia. This finding is consistent with the results in most previous reports. This trial was registered at ClinicalTrials.gov: NCT00712517.

[Venous ulcer]. / Das venöse Ulcus cruris.

Venous disorders causing a permanent increase in venous pressure are by far the most frequent reason for ulcers of the lower extremity. With a prevalence of 1 % in the general population rising to 4 % in the elderly over 80 and its chronic character, 1 % of healthcare budgets of the western world are spent on treatment of venous ulcers. A thorough investigation of the underlying venous disorder is the prerequisite for a differenciated therapy. This should comprise elimination of venous reflux as well as local wound management. Chronic ulcers can successfully be treated by shave therapy and split skin grafting. Compression therapy is a basic measure not only in venous ulcer treatment but also in prevention of ulcer recurrence. Differential diagnosis which have to be considered are arterial ulcers, vasculitis and neoplasms.

[Surgery of varicose vein insufficiency]. / Operative Therapie der Varikose.

The basis of surgery of great saphenous vein insufficiency is the concept of "privat circulation" coined by Trendelenburg in 1891. It was only logical that the dissection of the insuffcient vein or it's partial or complete resection could bring about healing. Over the years varicose vein stripping was modified to finally result in the highly effectiv concept of crossectomy and stripping. For decades this was the Goldstandard in surgery of varicose vein insufficiency. All the other minimally invasive therapeutic techniques which have been developed in the last decades had to compete with crossectomy and stripping. Thanks to progress in technical development the classic stripping procedure has been replaced by highly effectiv, minimally invasiv procedures, at least in the western industrialisied countries. For a minority of patients with specific anatomical pathologies as well as countries with limited health resources vein stripping remains a surgical standard procedure.

Surgical treatment of large vascular leg ulcers: a retrospective review evaluating risk factors for healing and recurrence.

BACKGROUND: Superficial reflux ablation and revascularization improve the long-term prognosis of venous and arterial leg ulcers but do not solve the problem of protracted healing of large chronic wounds. Skin grafting has been shown to successfully heal chronic leg ulcers. OBJECTIVE: To identify risk factors for ulcer healing and recurrence after shave therapy and split-skin grafting in patients with large ulcers treated surgically for venous insufficiency. METHODS: Single-center retrospective cohort study involving 72 chronic leg ulcers with a mean area of 77 ± 132 cm. Healing and recurrence rates were determined using life-table analysis. Clinical, demographic, and hemodynamic parameters were correlated with healing and recurrence using Cox regression analysis. RESULTS: Sixty ulcers (83%) healed after a mean of 1.9 months and 15 ulcers (25%) recurred after a mean of 12.7 months. Healing was positively associated with compression treatment (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.14-3.59) and negatively associated with ulcer duration (HR: 0.99, 95% CI: 0.98-1.0). Male sex, ulcer duration, and deep venous reflux were identified as significant risk factors for ulcer recurrence (HR: 0.14, 95% CI: 0.03-0.73; HR: 1.02, 95% CI: 1.0-1.04; and HR: 5.4, 95% CI: 1.30-22.31). CONCLUSION: Early surgical intervention improves healing and reduces the risk of ulcer recurrence.

Healing process of venous ulcers: the role of microcirculation.

In order to describe adequately the process of healing in the intermediate degrees, we investigated microcirculatory changes in the venous ulcers at well-defined stages of wound repair. We investigated dynamic changes in microcirculation during the healing process of venous ulcers. Ten venous ulcers were investigated in three consecutive clinical stages of wound healing: non granulation tissue (NGTA), GTA and scar. Subpapillary microcirculation was measured by laser Doppler perfusion (LDP) imaging and expressed using LDP values in arbitrary units. Nutritive perfusion by capillary microscopy and expressed as capillary density (CD) - the number of capillaries per square millimetre. Before the development of GTA the LDP was low (median 1·35; lower-upper quartiles 0·71-1·83) accompanied with zero CD in all but one patient who had a density of 1. With the first appearance of GTA in the same area, the LDP was improved (2·22; 1·12-2·33; P = 0·0024) when compared with NGTA, in combination with a significant increase in CD (1·75; 0-3; P = 0·0054). In scar, the LDP was similar to that in the NGTA (1·03; 0·77-1·83; P = 0·278), combined with the highest CD (5·75; 4·5-8) in comparison with the previous stages of the area (for both pairs, P < 0·0001). Venous ulcers are caused by poor nutritive and subpapillary perfusion. Subpapillary perfusion plays a major role in the formation of GTA. In a scar, the increased nutritive perfusion is sufficient to cover the blood supply and keep skin viable while subpapillary perfusion is low.

[Minimally invasive catheters in varicose vein treatment : New gold standard?] / Minimal-invasive Katheterverfahren in der Varizentherapie : Neuer Goldstandard?

BACKGROUND: Endovenous procedures are commonly used for varicose vein treatment. OBJECTIVES: Types, functionality, and significance of endovenous devices. METHODS: To describe the different endovenous devices, their mode of action, inherent risks and efficacy according to the literature. RESULTS: Long-term data confirm that endovenous procedures are equally effective as open surgery. Postoperative pain is minimal and downtime shorter after catheter interventions. CONCLUSION: Catheter-based endovenous procedures increase the diversity of varicose vein treatment options. They are preferred by patients due to less pain and shorter downtime.

Does endovenous laser ablation induce endothelial damage at the saphenofemoral junction?

BACKGROUND AND OBJECTIVE: One of the possible complications of endovenous laser ablation (EVLA) is thrombus progression into the common femoral vein or popliteal vein with the potential risk of pulmonary embolism or stroke. We set out to investigate the effect of laser energy applied under standardized treatment conditions on biomarkers of platelet and endothelial activation and on the hemostatic system. METHODS: Twenty patients with incompetence of the great saphenous vein were included in this prospective study. Blood samples of the iliofemoral and anticubital veins were collected before, during, and after EVLA. Plasma levels of soluble (s) P-selectin, soluble thrombomodulin (sTM), prothrombin fragment F1+2 (F1+2), and d-dimer were measured. (s) P-selectin and sTM were analyzed as surrogate markers of endothelial and platelet activation. F1+2 and d-dimer were monitored to quantify the degree of surgical trauma. RESULTS: Whereas there was no immediate rise of (s) P-selectin and sTM plasma concentrations in iliofemoral or anticubital blood, plasma levels of F1+2 and d-dimer increased significantly after EVLA. CONCLUSION: Pulsed mode laser ablation with an 810-nm fiber does not induce measurable platelet and endothelium activation in the iliofemoral or systemic blood. Furthermore, the immediate surgical trauma associated with EVLA appears to be modest. The authors have indicated no significant interest with commercial supporters.

Microstructural comparative analysis of calcification patterns in calciphylaxis versus arteriolosclerotic ulcer of Martorell.

BACKGROUND: Calciphylaxis and the arteriolosclerotic ulcer of Martorell (ASUM) represent two entities of cutaneous calcific arteriolopathies. Their differential diagnosis can be challenging, given similarities in their clinical and histological presentation. Calcification patterns have been proposed as a possible discriminative histological criterion, however, a systematic microstructural comparative analysis is lacking. OBJECTIVES: The study aimed at a systematic comparative microstructural analysis of the calcification patterns in calciphylaxis versus ASUM. MATERIALS & METHODS: Skin biopsies of patients with leg ulcers due to calciphylaxis (20) and ASUM (69) diagnosed at three European wound care centres (Vienna, Bern, Zurich) were included. The extent of calcification, arteriolar calcification pattern and presence of extra-arteriolar calcification were assessed. RESULTS: All calciphylaxis and most ASUM patients (77%) presented with arteriolar calcification. Although the mean number of calcified vessels and the proportion of calcified area were significantly higher in calciphylaxis specimens (p = 0.003 and p = 0.0171), there was no significant difference in the pattern of arteriolar calcification (p = 0.177). Interestingly, extra-arteriolar calcification was detected in the majority of both calciphylaxis (93.3%) and ASUM samples (85.2%, p = 0.639). Notably, Alizarin Red S staining was superior to H&E for the detection of calcifications of both entities (p = 0.014 and p < 0.0001), and to von Kossa staining for ASUM samples (p = 0.0001). However, no differences could be observed between cases with uraemic and non-uraemic calciphylaxis or ulcerations located on the upper and lower leg. CONCLUSION: Our results indicate that extra-arteriolar calcification is not only present in calciphylaxis, but can also be detected in ASUM suggesting a lack of specificity for this finding. However, more specific calcification stains, such as Alizarin Red S, should be used in suspected cases, as calcifications may be overlooked using conventional H&E staining.

[Varicose veins: disfigurement or disease?]. / Varikose: Schönheitsfehler oder Erkrankung?

According to one's subjective appraisal varicose veins will be perceived as more or less disfiguring. About 60% of the population suffer from only minor variants of varicose veins which bear no risk to health. A certain percentage will develop progressive disease with the venous ulcer representing the worst variant of chronic venous insufficiency. As long as there is no progressive disease, therapeutic modalities also account for a superior cosmetic appearance. Endoluminal procedures in particular meet with the claim for a superior treatment result with respect to cosmetic outcome without diminution of efficiency. In case of progressive venous insufficiency appearance is of inferior importance. About 70% of venous ulcers are due to primary varicose veins. Surgery of all accessible superficial refluxing veins is important to prevent recurrence. Compression treatment is highly effective in preventing chronic venous insufficiency and in venous ulcer treatment. About 60% of venous ulcers heal within a 24-week treatment period.

Extended monitoring of hemostatic activation after varicose vein surgery under general anesthesia.

BACKGROUND: Postoperative heparin prophylaxis after stripping of the long saphenous vein is a matter of controversial discussion, and practices vary by surgeon and country. OBJECTIVE: The aim of this study was to assess the extent of hypercoagulability by continued monitoring of activation markers of coagulation and fibrinolysis for a period of 3 weeks after stripping of the long saphenous vein and concomitant phlebectomy. METHODS: Including 21 patients, the following markers were measured preoperatively and on postoperative day 1, 2, 3, 7, 14, and 21: Activation products of coagulation: thrombin-antithrombin complex (TAT), thrombus precursor protein (TPP), and prothrombin-fragment F1+2 (F1+2), and markers of fibrinolysis: plasmin-alpha(2)-antiplasmin complexes (PAP), D-Dimer, tissue plasminogen activator (t-PA) antigen, and plasminogen activator inhibitor 1 (PAI-1) antigen. RESULTS: TAT levels increased significantly until day 3 (p=.008) and normalized within 14 days. TPP levels increased significantly until day 7 (p=.02), decreasing to initial values within 21 days. PAP complexes increased significantly until day 2 (p=.02) reducing to baseline within the observation period. D-Dimer levels increased immediately after surgery (p<.001) until day 14 (p<.001) and returned to baseline until day 21. CONCLUSIONS: Significant hemostatic activation after varicose vein surgery was observed and persisted until 3 weeks postoperatively, indicating that heparin prophylaxis for 2 to 3 weeks is advisable for at-risk patients.

Paraneoplastic pemphigus in association with hepatocellular carcinoma.

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous blistering disease associated with neoplasms, most frequently of the lymphoproliferative type. Rare PNP cases related to nonhematological solid tumors have been reported. The patient in this report presented with severe mucocutaneous involvement of PNP associated with hepatocellular carcinoma. Histopathology showed vacuolar interface dermatitis with keratinocyte necrosis and intraepidermal acantholysis. Direct immunofluorescence exhibited deposition of intercellular IgG and complement and granular complement at the dermoepidermal junction. Indirect immunofluorescence testing showed a typical intercellular staining on monkey esophagus and rat bladder epithelium. Immunoprecipitation showed characteristic target antigens of 250, 210, and 190 kDa molecular weights. This patient met all diagnostic criteria for paraneoplastic pemphigus and is, to our knowledge, the first report of a case associated with hepatocellular carcinoma.