A randomized trial of early endovenous ablation in venous ulceration: a critical appraisal: Original Article: Gohel MS, Heatly F, Liu X et al. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med 2018; 378:2105-114.

AIM: Gohel et al. aimed to compare early endovenous ablation vs. deferred endovenous ablation of superficial venous reflux with regard to time to healing of venous leg ulcers, rate of healing at 24 weeks, recurrence rate, ulcer-free time and health-related quality of life. SETTING AND DESIGN: This multicentre, parallel-group (ratio 1 : 1), randomized controlled trial was conducted in a vascular surgery department setting at 20 participating centres across the U.K. STUDY EXPOSURE: A total of 450 patients with venous leg ulcers were randomly assigned to receive compression therapy and undergo early endovenous ablation of superficial venous reflux within 2 weeks after randomization (early-intervention group) or to receive compression therapy alone, with consideration of endovenous ablation deferred until after the ulcer was healed or until 6 months after randomization if the ulcer was unhealed (deferred-intervention group). OUTCOMES: The primary outcome was the time to ulcer healing. Secondary outcomes were the rate of ulcer healing at 24 weeks, the rate of ulcer recurrence, the length of time free from ulcers (ulcer-free time) during the first year after randomization, and patient-reported health-related quality of life. TRIAL INTERVENTIONS: Endovenous laser or radiofrequency ablation, ultrasound-guided foam sclerotherapy, or nonthermal, nontumescent methods of treatment (such as cyanoacrylate glue or mechanochemical ablation) were performed either alone or in combination. The treating clinical team determined the method and strategy of endovenous treatment. RESULTS: The time to ulcer healing was shorter in the early-intervention group than in the deferred-intervention group. Furthermore, more patients had healed ulcers with early intervention [hazard ratio for ulcer healing 1·38, 95% confidence interval (CI) 1·13-1·68; P = 0·001]. The median time to ulcer healing was 56 days (95% CI 49-66) in the early-intervention group and 82 days (95% CI 69-92) in the deferred-intervention group. The rate of ulcer healing at 24 weeks was 85·6% in the early-intervention group and 76·3% in the deferred-intervention group. The median ulcer-free time during the first year after trial enrolment was 306 days (interquartile range 240-328) in the early-intervention group and 278 days (interquartile range 175-324) in the deferred-intervention group (P = 0·002). The most common complications were pain and deep vein thrombosis (DVT) (early-intervention group: pain, six of 28; DVT, nine of 28; deferred-intervention group: pain, six of 24; DVT, three of 24). CONCLUSIONS: Gohel et al. conclude that early endovenous ablation of superficial venous reflux results in faster healing of venous leg ulcers than deferred endovenous ablation. Patients assigned to the early-intervention group also had longer ulcer-free time during the first year after randomization.

[Skin ulcerations due to CINCA syndrome and its successful treatment with prostaglandin E1]. / Kutane Ulzerationen bei CINCA­Syndrom und ihre erfolgreiche Behandlung durch Prostaglandin E1.

Chronic infantile neurological cutaneous and articular syndrome (CINCA) is a disorder with a defect in the CIAS1 (NLRP3) gene and the altered gene product cryopyrin leads to inflammasome activation with increased IL-1beta synthesis. The activation pathway of the transcription factor NF-κB is also affected, which plays a role in angiogenesis. With respect to the angiogenesis stimulating ability of prostaglandin E1, we treated a female patient with CINCA syndrome and conventionally non-responsive skin ulcers with prostaglandin E1 infusions (6 µg/kg bw/24 h/5 day) followed by wound healing lasting over 3 weeks. After 1 year of periodic infusions, the skin defects were permanently closed.

Skin signs of primary immunodeficiencies: how to find the genes to check.

Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases that result from defects in immune system development and/or function. The clinical manifestations of PIDs are highly variable, but most disorders involve at least an increased susceptibility to infection. Furthermore, cutaneous manifestations are very common in PIDs. As an easily accessible organ, the skin can be crucial for early diagnosis and treatment. This is relevant for preventing significant disease-associated morbidity and mortality. We provide a table that enables the reader to find the possible diseases and corresponding gene defects based on the skin manifestations of the suspected PIDs. To our knowledge, this is the first review that allows the reader to find relevant PIDs and the respective gene defects through solitary or combined skin signs.

Perfusion quantification of vascular malformations using contrast-enhanced ultrasound (CEUS) with time intensity curve analysis before and after treatment: First results.

AIM: Aim of this pilot-study was to quantify perfusion changes of vascular malformations before and after the first interventional treatment using contrast-enhanced ultrasound (CEUS). MATERIAL AND METHODS: 29 patients (10 male, 19 female) between 6 and 63 years (mean 28.1 years) with 12 arterio-venous (AVM) and 17 venous malformations (VM) were examined before and after their first percutaneous interventional treatment. CEUS was performed with a 2.4 ml bolus injection of sulfur-hexafluorid microbubbles, and a 6-9 MHz mulitfrequency transducer. A 60 sec cine sequence was recorded and regions of interest (10 mm×30 mm) were defined in the centre, and the margins of the vascular malformation as well as in the surrounding healthy tissue. Time Intensity Curves (TIC) were analysed, and Time to Peak (TTP) as well as Area under the Curve (AUC) were calculated. RESULTS: For VM there was a significant perfusion difference (p < 0.05) in AUC between centre and the surrounding tissue before (323.1 vs. 130.4 rU) and after treatment (331.0 vs. 106.9 rU). There was no significant difference for TTP in ROIs of VM (19.1 vs. 26.5 sec). After the treatment there was a significant decrease in AUC for all three regions in AVMs, and an increase in TTP for AVM. However TTP for AVM in the centre ROI still remained shorter than in the surrounding tissue even after therapy (20.9 vs. 25.4 sec). CONCLUSION: CEUS with TIC analysis is a promising imaging method for the evaluation of perfusion before and after percutaneous treatment of vascular malformations. AUC decrease indicates therapy-induced changes in perfusion of VM whereas an increase in TTP shows therapy-related changes in AVM.

Indocyanine green-augmented diode laser treatment of port-wine stains: clinical and histological evidence for a new treatment option from a randomized controlled trial.

BACKGROUND: Complete clearance of port-wine stains (PWS) is difficult to achieve, mainly because of the resistance of small blood vessels to laser irradiation. Indocyanine green (ICG)-augmented diode laser treatment (ICG+DL) may overcome this problem. OBJECTIVES: To evaluate the feasibility of ICG+DL therapy of PWS and to compare the safety and efficacy of ICG+DL with the standard treatment, flashlamp-pumped pulsed dye laser (FPDL). METHODS: In a prospective randomized controlled clinical study, 31 patients with PWS were treated with FPDL (λ(em)=585 nm, 6 J cm(-2) , 0.45 ms pulse duration) and ICG+DL (λ(em)=810 nm, 20-50 J cm(-2) , 10-25 ms pulse duration, ICG-concentration: 2 mg kg(-1) body weight) in a split-face modus in one single treatment setting that included histological examination (haematoxylin and eosin, CD34). Two blinded investigators and the patients assessed clearance rate, cosmetic appearance and side-effects up to 3 months after treatment. RESULTS: ICG+DL therapy induced photocoagulation of medium and large blood vessels (>20 µm diameter) but not of small blood vessels. According to the investigators' assessment, clearance rates and cosmetic appearance were better after ICG+DL therapy than after FPDL treatment (P=0.114, P=0.291, respectively), although not up to a statistically significant level, whereas patients considered these parameters superior (P=0.003, P=0.006, respectively). On a 10-point scale indicating pain during treatment, patients rated ICG+DL to be more painful (5.81 ± 2.12) than FPDL treatment (1.61 ± 1.84). CONCLUSION: ICG+DL represents a new and promising treatment modality for PWS, but laser parameters and ICG concentration need to be further optimized.

Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy.

BACKGROUND: The field cancerization concept in photodamaged patients suggests that the entire sun-exposed surface of the skin has an increased risk for the development of (pre)-malignant lesions, mainly epithelial tumours. Topical photodynamic therapy (PDT) is a noninvasive therapeutic method for multiple actinic keratosis (AK) with excellent outcome. OBJECTIVES: To evaluate the clinical, histological and immunohistochemical changes in human skin with field cancerization after multiple sessions of PDT with methyl-aminolaevulinate (MAL). METHODS: Twenty-six patients with photodamaged skin and multiple AK on the face received three consecutive sessions of MAL-PDT with red light (37 J cm(-2)), 1 month apart. Biopsies before and 3 months after the last treatment session were taken from normal-appearing skin on the field-cancerized area. Immunohistochemical stainings were performed for TP-53, procollagen-I, metalloproteinase-1 (MMP-1) and tenascin-C (Tn-C). RESULTS: All 26 patients completed the study. The global score for photodamage improved considerably in all patients (P < 0·001). The AK clearance rate was 89·5% at the end of the study. Two treatment sessions were as effective as three MAL-PDT sessions. A significant decrease in atypia grade and extent of keratinocyte atypia was observed histologically (P < 0·001). Also, a significant increase in collagen deposition (P = 0·001) and improvement of solar elastosis (P = 0·002) were noticed after PDT. However, immunohistochemistry showed only a trend for decreased TP-53 expression (not significant), increased procollagen-I and MMP-1 expressions (not significant) and an increased expression of Tn-C (P = 0·024). CONCLUSIONS: Clinical and histological improvement in field cancerization after multiple sessions of MAL-PDT is proven. The decrease in severity and extent of keratinocyte atypia associated with a decreased expression of TP-53 suggest a reduced carcinogenic potential of the sun-damaged area. The significant increase of new collagen deposition and the reduction of solar elastosis explain the clinical improvement of photodamaged skin.

Skin signs in diabetes mellitus.

Diabetes mellitus is the most common endocrine disorder with continuously increasing prevalence. Blood vessels, nerves, eyes, kidneys and skin are affected, which causes both an enormous financial burden and a reduced quality of life of the affected patients. Long-standing diabetes may impair skin homeostasis resulting in skin manifestations in at least one third of all diabetics. The skin involvement may be the first presenting sign of diabetes, thus the respective skin signs should lead to diabetes focused diagnostic. Besides, the skin signs may be considered as a marker for the course of the disease or for the success of therapeutic interventions.

Cytokines, chemokines and growth factors in wound healing.

In wound healing, a variety of mediators have been identified throughout the years. The mediators discussed here comprise growth factors, cytokines and chemokines. These mediators act via multiple (specific) receptors to facilitate wound closure. As research in the last years has led to many new findings, there is a need to give an overview on what is known, and on what might possibly play a role as a molecular target for future wound therapy. This review aims to keep the reader up to date with selected important and novel findings regarding growth factors, cytokines and chemokines in wound healing.

The impact of 10% α-hydroxy acid emulsion on skin pH.

BACKGROUND/AIMS: The effects of a 10% α-hydroxy acid (AHA) oil/water (O/W) emulsion on the pH of human skin surface (pH(ss)) and stratum corneum (SC; pH(sc)) were evaluated in vivo. METHODS: The AHA O/W emulsion was applied to an area on the volar forearm of male volunteers (n = 12), and then wiped off after 10 min. Prior to application and over the following 3 h, the pH(ss) was measured. We used glass electrode measurements and time domain dual lifetime referencing (tdDLR) with luminescent sensor foils. In another experiment (n = 5), the impact of the AHA O/W emulsion on the pH(sc) gradient was measured by tape stripping of the SC of the volar forearm after application of the AHA O/W emulsion. RESULTS: Compared with pH(ss) values prior to treatment [5.2 ± 1.7 (tdDLR) or 4.8 ± 0.5 (electrode)], the pH(ss) was significantly reduced 10 min after application [4.0 ± 0.3 (tdDLR) or 4.1 ± 0.1 (electrode)] and the pH(ss) remained significantly reduced over the measurement period of 3 h [after 3 h: 4.4 ± 0.2 (tdDLR) or 4.5 ± 0.3 (electrode)]. The AHA O/W emulsion significantly reduced the pH(sc) even down to deep layers of the SC. CONCLUSION: After a 10-min application time, the 10% AHA O/W emulsion reduces the pH(ss) (for at least 3 h) and pH(sc) in deep layers of the SC.

[Cutaneous amyloidosis]. / Kutane Amyloidosen.

Amyloids are common protein aggregates in nature. Some amyloids fulfill important biological tasks while others are known to cause diseases. Despite the fact that the ultrastructure of amyloid is highly conserved, the mechanism of amyloidogenesis remains a challenging research topic. In humans, amyloidoses may develop in the skin or lead to skin signs due to secondary cutaneous involvement. An accurate diagnostic procedure is crucial for planning the therapy of this heterogeneous group of diseases. Therefore, the aim of this paper is to give an overview on the different kinds of amyloidoses as well as on diagnostic and therapeutic approaches. Furthermore, the discrimination between functional and disease-causing amyloid is briefly presented.

[Cutaneous wound healing. Therapeutic interventions]. / Wundheilung. Therapeutische Interventionen.

In modern medicine chronic wounds are an interdisciplinary major therapeutic and financial issue. Essential for therapy is both the causal treatment of the underlying disease and the symptomatic treatment depending on the phase of wound healing. The physiological process of cutaneous wound healing is divided into three overlapping phases: inflammation, proliferation and tissue remodelling. The choice of a suitable therapy depends on the extent of the wound, the localization, exudation and bacterial infestation. In recent years a number of novel findings were made about this complex biological process and the insights gained have resulted in new therapeutic concepts. In the following article we give an overview about possible therapeutic options and present the various modern wound dressings.

Oxygen in acute and chronic wound healing.

Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defence, angiogenesis and collagen synthesis. Even though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. This article provides an overview on the role of oxygen in wound healing and chronic wound pathogenesis, a brief insight into systemic and topical oxygen treatment, and a discussion of the role of wound tissue oximetry. Thus, the aim is to improve the understanding of the role of oxygen in wound healing and to advance our management of wound patients.