Increasing Morbidity with Extent of Lymphadenectomy for Primary Malignant Melanoma.

BACKGROUND: According to current guidelines, complete lymphadenectomy (LAD) is indicated in melanoma patients with a positive sentinel lymph node. Whereas there is little evidence from randomized trials for a survival benefit of this procedure, its morbidity is not trivial. We aimed to assess clinical associations between risk factors and complications of LAD to guide decision making about this aspect of melanoma management. METHODS AND RESULTS: A cohort of 174 patients who had undergone LAD for primary melanoma was retrospectively analyzed, and multivariable logistic regression models were used to correlate patient risk factors, tumor characteristics, number of excised lymph nodes, and procedural details with the incidence of complications. The overall rate of LAD-associated complications was 41.4%, 33.9% being lymphatic complications. The number of excised lymph nodes was independently associated with development of lymphatic complications (odds ratio 3.90/12.78 if more than 10/20 lymph nodes had been removed, p = 0.01/<0.001, respectively). However, the number of excised lymph nodes had no influence on overall survival using a multivariable Cox proportional hazards regression analysis. CONCLUSIONS: In this retrospective cohort study, an important association was found between the extent of LAD and lymphatic complications. Further studies should evaluate the necessity and extent of aggressive LAD to balance survival benefit with morbidity of LAD procedures.

Impact of a Glycolic Acid-Containing pH 4 Water-in-Oil Emulsion on Skin pH.

The skin pH is crucial for physiological skin functions. A decline in stratum corneum acidity, as observed in aged or diseased skin, may negatively affect physiological skin functions. Therefore, glycolic acid-containing water-in-oil (W/O) emulsions adjusted to pH 4 were investigated regarding their effect on normal or increased skin pH. A pH 4 W/O emulsion was applied on three areas with pathologically increased skin surface pH in diabetics (n = 10). Further, a 28-day half-side trial (n = 30) was performed to test the long-term efficacy and safety of a pH 4 W/O emulsion (n = 30). In summary, the application of a pH 4 W/O emulsion reduced the skin pH in healthy, elderly and diabetic subjects, which may improve epidermal barrier functions.

Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic wounds that disrupt epidermal repair.

Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing. Extracellular pH (pHe) is precisely regulated and potentially important in signaling within wounds due to its diverse cellular effects. Additionally, sufficient oxygenation is a prerequisite for cell proliferation and protein synthesis during tissue repair. It was, however, impossible to study these parameters in vivo due to the lack of imaging tools. Here, we present luminescent biocompatible sensor foils for dual imaging of pHe and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI), respectively. With these dual sensors, we discovered centripetally increasing pHe-gradients on human chronic wound surfaces. In a therapeutic approach, we identify pHe-gradients as pivotal governors of cell proliferation and migration, and show that these pHe-gradients disrupt epidermal barrier repair, thus wound closure. Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe-gradients in perturbed healing. We also found that pHe-gradients on chronic wounds of humans are predominantly generated via centrifugally increasing pHe-regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of pHe on chronic wound surfaces poses a promising strategy to improve healing. The study has broad implications for cell science where spatial pHe-variations play key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented herein can be used to visualize pHe and oxygenation in various biomedical fields.

Diet-induced pigmented purpuric dermatosis.

Pigmented purpuric dermatoses (PPD) are chronic and relapsing disorders characterised by a localised or generalised purpuric rash. Even though the clinical presentation of PPD subtypes varies, they have a similar histopathology. The aetiology is largely unknown, but trigger factors, such as drugs, infections and systemic illnesses have been described. To our knowledge, this is the only case showing widespread PPD lesions not only induced but also rapidly provoked by dietary factors, namely Coca Cola and apple-cherry fruit spritzer.

A randomized controlled trial to optimize indocyanine green-augmented diode laser therapy of capillary malformations.

BACKGROUND: Indocyanine green (ICG)-augmented diode laser therapy (ICG + DL) represents a new treatment modality for capillary malformations (CM). However, an increase of the ICG-concentration or the use of an intense pulsed light (IPL) device as light source may further optimize treatment outcomes in CM. OBJECTIVE: This proof-of-concept trial including 15 patients (skin type II to III) with CM evaluated the efficacy and safety of ICG-augmented diode laser therapy (808 nm) at a total dose of 4 mg/kg body weight (b.w.). Additionally, five patients with extensive CM received IPL therapy before and after ICG-administration (ICG + IPL). METHODS: ICG was intravenously administered to 15 patients with CM at a total dose of 4 mg/kg b.w. Immediately after ICG injection, diode laser pulses with different radiant exposures (20-110 J/cm(2) ) were applied as one single treatment. Five patients with extensive CM additionally received IPL (555-950 nm) therapy. Safety and efficacy were assessed both 1 and 3 months after the single treatment by a blinded investigator and the patient. Furthermore, color of the CM was objectively measured by means of a color meter (colorStriker™, Eduard Mathai GmbH, Hannover, Germany). Treatment with the flashlamp-pumped pulsed dye laser (FPDL) and the IPL alone (five patients) served as reference treatment. RESULTS: According to the assessment by the patients and the blinded investigator, the clearance rate was slightly better after ICG + DL therapy than after FPDL treatment (P = 0.1, P = 0.8). In one out of five patients, IPL with and without ICG injection induced poor to moderate clearance of CM and persisting erythema in another patient. The correlation between the visual assessment by the blinded investigator and the colorimetric measurements was poor. CONCLUSION: A minority of patients with CM may benefit from ICG + DL therapy, but efficacy cannot be improved by higher ICG doses.

Sudden sensorineural hearing loss: systemic steroid therapy and the risk of glucocorticoid-induced hyperglycemia.

Sudden sensorineural hearing loss is usually treated with systemic glucocorticoids. Intratympanic injections of glucocorticoids offer a possibly equivalent treatment alternative, avoiding adverse systemic effects on blood glucose. We, therefore, investigated the extent to which different doses of systemic glucocorticoid therapy affects blood glucose levels. We conducted a retrospective analysis of treatment courses in 179 patients from the Departments of Otorhinolaryngology, Ophthalmology and Dermatology who underwent short-course systemic glucocorticoid therapy. Patients were subdivided into three groups on the basis of their cumulative prednisolone dose from days 1 to 3 (Group 1: <750 mg; Group 2: 750-1,499 mg; Group 3: >1,499 mg); in addition, a distinction was made between diabetic and non-diabetic patients. Among the non-diabetic patients on days 2-4, diabetic levels of fasting blood glucose were detected significantly more often (P < 0.01) in Group 3 (67 %) than in Group 1 (28 %) and Group 2 (21 %). Furthermore, there was a highly significant mean Pearson correlation (r = 0.329; P < 0.01) between blood glucose levels and glucocorticoid dose. This correlation was even more pronounced in the diabetic patients (r = 0.51; P = 0.02). In this category, hyperglycemia was detected in 40 % of patients in Group 1, 63 % in Group 2 and 100 % in Group 3. The prevalence of glucocorticoid-induced hyperglycemia during systemic therapy is high and rises as the dose increases. This should be kept in mind when choosing the dosage. Besides, it should also be considered that even short-term hyperglycemia presents possible health risks and the risk of inducing diabetes. This is especially of interest as intratympanic therapy offers a possible alternative to the systemic application.

A sprayable luminescent pH sensor and its use for wound imaging in vivo.

Non-invasive luminescence imaging is of great interest for studying biological parameters in wound healing, tumors and other biomedical fields. Recently, we developed the first method for 2D luminescence imaging of pH in vivo on humans, and a novel method for one-stop-shop visualization of oxygen and pH using the RGB read-out of digital cameras. Both methods make use of semitransparent sensor foils. Here, we describe a sprayable ratiometric luminescent pH sensor, which combines properties of both these methods. Additionally, a major advantage is that the sensor spray is applicable to very uneven tissue surfaces due to its consistency. A digital RGB image of the spray on tissue is taken. The signal of the pH indicator (fluorescein isothiocyanate) is stored in the green channel (G), while that of the reference dye [ruthenium(II)-tris-(4,7-diphenyl-1,10-phenanthroline)] is stored in the red channel (R). Images are processed by rationing luminescence intensities (G/R) to result in pseudocolor pH maps of tissues, e.g. wounds.

Cosmetic and dermatologic use of alpha hydroxy acids.

Alpha hydroxy acids (AHAs), in particular glycolic acid, are a class of chemical compounds frequently used in cosmetics and dermatology. This review summarizes the current knowledge regarding chemistry, mechanism of action as well as the different indications ranging from cosmetic skin hydration to acne proven by clinical trials. Overall AHAs depending on the concentration used present an ingredient for cosmetic products or medical devices with proven efficacy.

Indocyanine green-augmented diode laser therapy of telangiectatic leg veins: a randomized controlled proof-of-concept trial.

BACKGROUND: Telangiectatic leg veins, which affect about 40-50% of adults, represent a frequent cosmetic rather than a medical problem. Besides sclerotherapy, various laser devices are common treatment options. However, complete clearance rates can only be achieved in a small number of patients. OBJECTIVE: In this proof-of-concept study, the safety and efficacy of indocyanine green (ICG)-augmented diode laser therapy (808 nm) was evaluated for the treatment of telangiectatic leg veins. METHODS: ICG (2 mg/kg body weight) was intravenously administered in 15 female patients (skin type II to III) with telangiectatic leg veins (measuring between 0.25 and 3 mm in diameter). Immediately after ICG injection, diode laser pulses with different radiant exposures (50-110 J/cm(2)) were applied as one single treatment. Safety and efficacy were assessed 1 and 3 months after treatment by a blinded investigator and the patient. Treatments with the pulsed dye laser (PDL) and the diode laser without ICG served as reference therapies. RESULTS: The safety of ICG application and diode laser treatment was excellent in all patients with no persisting side effects. Vessel clearance was dose-dependent. Diode laser treatment at radiant exposures between 100 and 110 J/cm(2) resulted in good vessel clearance, which even improved to excellent after the application of double pulses. Diode laser therapy without ICG and PDL treatment induced poor to moderate clearance of telangiectatic leg veins. CONCLUSION: ICG-augmented diode laser therapy has proved to be a safe and effective treatment option for telangiectatic leg veins.

Impact of age and body site on adult female skin surface pH.

BACKGROUND: pH is known as an important parameter in epidermal barrier function and homeostasis. AIM: The impact of age and body site on skin surface pH (pH(SS)) of women was evaluated in vivo. METHODS: Time domain dual lifetime referencing with luminescent sensor foils was used for pH(SS) measurements. pH(SS) was measured on the forehead, the temple, and the volar forearm of adult females (n = 97, 52.87 ± 18.58 years, 20-97 years). Every single measurement contained 2,500 pH values due to the luminescence imaging technique used. RESULTS: pH(SS) slightly increases with age on all three investigated body sites. There are no significant differences in pH(SS) between the three investigated body sites. CONCLUSION: Adult pH(SS) on the forehead, the temple and the volar forearm increases slightly with age. This knowledge is crucial for adapting medical skin care products.

Diagnostics of autoimmune bullous diseases in German dermatology departments.

BACKGROUND: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments. METHODS: A standardized questionnaire evaluated the available diagnostic methods i. e. direct immunofluorescence microscopy (IFM), indirect IFM, commercial ELISA systems, and non-commercial serological tests as well as the number of samples per year in all 34 university and 39 non-university dermatology departments. RESULTS: The overall return rate was 89 %, 100 % and 79 % for the university and non-university departments, respectively. Direct IFM was the most frequently used method and was applied in 98 % of the responding departments. In 74 % of the responding departments, indirect IFM was used mainly on monkey esophagus and human salt-split skin. Commercial ELISA systems were employed in 58 % of the clinics; all of them used anti-desmoglein ELISA, while anti-BP180 and anti-BP230 ELISA were established in 49 % and 48 % of departments, respectively. Non-commercial analytic methods were only performed in 22 % of the departments. CONCLUSIONS: The high return rate of this survey allows a relatively precise description of the current diagnostic methods used in German dermatology departments. Standard diagnostic tests are available nationwide and in bullous pemphigoid and pemphigus, the antigen-specific detection of autoantibodies is routinely performed in half of the departments. Rare disorders may be diagnosed by cooperation with some specialized centers.

Kyrle disease and acquired perforating collagenosis secondary to chronic renal failure and diabetes mellitus.

A 59-year-old man with chronic renal failure and diabetes mellitus presented with pruritic crusted lesions which histologically were perforating disorders, showing features of both Kyrle disease and acquired perforating collagenosis. The mechanisms of transepidermal elimination and the classification of perforating disorders are briefly discussed. Additionally, we question the concept of perforation, as epidermal damage and exposure of subepidermal substances may artificially present as perforation.

Treatment of leg veins with indocyanine green and lasers investigated with mathematical modelling.

PURPOSE: The treatment of leg veins is routinely performed in clinical practice using near infrared (NIR) lasers. However, due to low absorption of NIR light in blood vessels, the clinical results are still suboptimal. The absorption of the NIR light can be significantly increased with intravenous introduction of an indocyanine green (ICG) dye. In this work a mathematical model was used to delineate clinically valid settings for ICG and NIR lasers for the treatment of leg veins. METHODS: A finite element commercial package was used to simulate light propagation and absorption and heat generation in a skin-like geometry. The simulations were conducted for 755 nm and 810 nm light wavelengths, which are emitted by alexandrite and diode lasers, respectively. Five different laser settings, six different vessel diameters (0.1-2 mm) and three ICG concentrations (0, 1 or 2 mg/kg body weight (BW)) were used to calculate the temperature field spatial distribution as a function of time. RESULTS: The diameter of the blood vessels affects the temperature distribution during and following laser irradiation, with and without ICG. Adding 1 or 2 mg/kg bw of ICG will cause significant temperature increase (15-35°C, p ≤ 0.001) in blood vessels with a diameter of 0.1-1 mm and steep temperature gradients in 1.5-2 mm diameter blood vessels. CONCLUSIONS: Intravenous application of ICG at 1-2 mg/kg may improve coagulation of blood vessels with 0.1-1 mm diameter irradiated with either a diode or alexandrite laser. This should be confirmed with clinical trials in the near future.

Laser thermal therapy of benign skin tumours: review and update.

The goal of this review is to provide an overview on laser treatment of benign skin tumours and recent developments in this field. Ablational laser systems are established treatment devices for benign skin tumours. They obtain good cosmetic results with mostly minimal side-effects. Recently, fractional laser devices or combination of laser therapy with photodynamic therapy has gained attention in this field. However, there is a lack of randomised, controlled trials for laser treatment of benign skin tumours.