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.

Peptidase inhibitor 3 and chemokine ligand 27 may serve as biomarkers for actinic keratoses in organ transplant recipients.

Molecular profiling of tissue samples in organ transplant recipients (OTRs) may allow early and minimally invasive identification of actinic keratosis (AK). The aim of this study was to compare mRNA expression profiles of 13 genes, as putative genetic biomarkers of AK, before and after treatment using two different field therapies, and to correlate the results with histological and clinical parameters. For this single-centre prospective randomized intra-patient-controlled study, 10 OTRs with AKs were recruited for field therapy with two cycles of methyl-5-aminolevulinate 16% cream-photodynamic therapy (PDT) at one site and imiquimod 5% cream for four weeks at another site. AKs in the PDT area were reduced significantly at one, two, and six months after completion of the treatment (p < 0.001). The effect of imiquimod was weaker but still significant when evaluated during the same intervals (p < 0.001). By comparing the mRNA expression profiles of various genetic markers before, during, and three months after therapy, we observed specific patterns of expression for skin-derived peptidase inhibitor 3 (PI3) and chemokine ligand 27 (CCL27) in all groups, regardless of the treatment modality. Compared to healthy skin, the expression of PI3 was strongly decreased and that of CCL27 increased in AK lesions before therapy. The expression level of both genes showed a significant convergence to values observed in healthy skin in both groups after therapy. The pattern and level of specific gene expression in actinic keratoses could serve as a biomarker.

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.

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.

Oral vs. bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema.

BACKGROUND: Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema. However, most studies were retrospective and did not include longer follow-up periods. AIM: To compare the therapeutic efficacy, tolerability and duration of remission after oral vs. bath PUVA using 8-MOP in patients with chronic palmoplantar eczema. METHODS: Twenty-nine patients were randomly allocated to treatment with oral or bath PUVA. Treatment was given thrice weekly for a maximum of 20 weeks. The primary outcome measure was the improvement in eczema score at the end of treatment. After clearing patients were followed up until relapse or up to 40 months. RESULTS: Overall, both PUVA modalities appeared comparably effective. However, after stratifying according to eczema type, significant differences in therapeutic outcome in general as well as in response to the two regimes were found. Dyshidrotic eczema responded better to both treatments (P=0.048) and remained longer in remission than hyperkeratotic eczema. Hyperkeratotic eczema cleared significantly better with oral than with bath PUVA (P=0.03). CONCLUSION: Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.

Tigecycline has no effect on cytokine release in an ex vivo endotoxin model of human whole blood.

In previous studies, tetracyclines have been shown to decrease the release of cytokines in experimental settings of endotoxaemia. Tigecycline is the first member of the closely related glycylglycines and, due to its broad antimicrobial spectrum, it is considered useful in the treatment of sepsis. We therefore tested its ability to influence the concentrations of the proinflammatory cytokines interleukin (IL)-1beta, tumour necrosis factor-alpha (TNFalpha) and IL-6 in an established ex vivo model of human endotoxaemia. Whole blood from ten healthy volunteers was incubated with either saline (negative control), tigecycline (1 microg/mL [therapeutic concentration] or 100 microg/mL [supratherapeutic concentration]), lipopolysaccharide (LPS; 50 pg/mL, control) or a combination of tigecycline plus LPS (test group). Concentrations of IL-1beta, TNFalpha and IL-6 in the supernatant were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. As expected, incubation with LPS significantly increased the cytokine concentrations in whole blood compared with baseline (P<0.05). The combination of tigecycline plus LPS did not exert any significant effect on the concentrations of IL-1beta, IL-6 and TNFalpha after 2h and 4h of incubation compared with LPS alone. These results indicate that proinflammatory cytokines remained unaffected by tigecycline in an established ex vivo model of systemic inflammatory response.

Orally administered rapamycin, dacarbazine or both for treatment of human melanoma evaluated in severe combined immunodeficiency mice.

OBJECTIVE: In this experimental study, the antineoplastic potential of orally administered rapamycin in human melanoma was evaluated and compared with dacarbazine (DTIC) as well as with the antineoplastic effect of the combination of both drugs. METHODS: The substances were tested using 2 human melanoma cell lines, 518A2, which is highly susceptible to DTIC, and 607B, which is moderately susceptible. A human melanoma severe combined immunodeficiency mouse xenotransplantation model was used. After development of palpable tumors, mice received oral rapamycin or saline over 18 days. Additionally, from treatment day 4 to 8, mice were randomly chosen to receive either DTIC or saline treatment. RESULTS: The oral rapamycin treatment (1.5, 7.5, 15 and 30 mg/kg body weight) had an antineoplastic effect, ranging from 35 to 78% tumor weight reduction compared with the saline group. In DTIC less sensitive 607B tumors, rapamycin treatment (15 and 30 mg/kg body weight) was superior to DTIC treatment (p < 0.05). DTIC monotreatment reduced tumor weight in 518A2 tumors by 85% on average, whereas in 607B xenografts, no significant tumor weight reduction was observed compared with the saline group (p > 0.05). The combination of rapamycin and DTIC was not superior to rapamycin monotreatment in any cell line. CONCLUSION: These data indicate that oral rapamycin exerts a relevant antineoplastic effect on human melanoma cells. This effect appeared to be more pronounced in DTIC less sensitive melanoma xenografts.