Preventive health examinations: protocol for a prospective cross-sectional study of German employees aged 45 to 59 years (Ü45-check).

Objective: Early identification of health-related risk factors is of great importance for maintaining workability. Screening examinations can help to detect diseases at an early stage and provide more needs-based recommendations. This study aims (1) to assess the individual need for prevention or rehabilitation based on preventive health examinations compared to a questionnaire survey, (2) to assess the results of the preventive health examinations compared to the Risk Index - Disability Pension (RI-DP), (3) to assess the results of the questionnaire survey compared to the RI-DP, (4) to assess the general health status of the sample (target population > 1,000) in German employees aged 45-59, (5) to identify the most common medical conditions. A further study question aims, and (6) to investigate the general health status of the specific occupational groups. Methods: Comprehensive diagnostics including medical examination, anamnesis, anthropometric measurements, bioelectrical impedance analysis (BIA), handgrip strength, resting electrocardiogram (ECG), resting blood pressure, pulse wave velocity (PWV), and laboratory blood analyses added by a questionnaire are conducted. The research questions are analyzed in an exploratory manner. Results and conclusion: We expect that the results will allow us to formulate recommendations regarding screening for prevention and rehabilitation needs on a more evidence-based level.Clinical Trial Registration: DRKS ID: DRKS00030982.

Role of IL-17 in atopy-A systematic review.

PURPOSE OF REVIEW: Atopy is defined as the genetic predisposition to react with type I allergic diseases such as food-, skin-, and respiratory allergies. Distinct molecular mechanisms have been described, including the known Th2 driven immune response. IL-17A (IL-17) is mainly produced by Th17 cells and belongs to the IL-17 family of cytokines, IL-17A to F. While IL-17 plays a major role in inflammatory and autoimmune disorders, more data was published in recent years elucidating the role of IL-17 in allergic diseases. The present study aimed to elaborate specifically the role of IL-17 in atopy. METHODS: A systematic literature search was conducted in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials, regarding IL-17 and atopy/allergic diseases. RESULTS: In total, 31 novel publications could be identified (food allergy n = 3, allergic asthma n = 7, allergic rhinitis [AR] n = 10, atopic dermatitis [AD] n = 11). In all allergic diseases, the IL-17 pathway has been investigated. Serum IL-17 was elevated in all allergic diseases. In AR, serum and nasal IL-17 levels correlated with the severity of the disease. In food allergies, serum IL-17E was also elevated in children. In AD, there is a trend for higher IL-17 values in the serum and skin specimen, while it is more expressed in acute lesions. In allergic asthma, serum IL-17 levels were increased. In two studies, higher serum IL-17 levels were found in severe persistent asthmatic patients than in intermittent asthmatics or healthy controls. Only one therapeutic clinical study exists on allergic diseases (asthma patients) using a monoclonal antibody against the IL-17 receptor A. No clinical efficacy was found in the total study population, except for a subgroup of patients with (post-bronchodilator) high reversibility. SUMMARY: The role of IL 17 in the pathogenesis of allergic diseases is evident, but the involvement of the Th17 cytokine in the pathophysiological pathway is not conclusively defined. IL-17 is most likely relevant and will be a clinical target in subgroups of patients. The current data indicates that IL-17 is elevated more often in acute and severe forms of allergic diseases.

From Melanocytes to Melanoma Cells: Characterization of the Malignant Transformation by Four Distinctly Different Melanin Fluorescence Spectra (Review).

The melanin fluorescence emitted by pigment cells of the human skin has been a central research topic for decades, because melanin, on the one hand, protects against (solar) radiation in the near-UV range, whereas on the other hand, melanocytes are the starting point for the malignant transformation into melanoma. Until recently, however, melanin fluorescence was not accessible in the context of conventional spectroscopy, because it is ultraweak and is overshadowed by the more intense so-called autofluorescence of endogenous fluorophores. The advent of a new method of laser spectroscopy has made this melanin fluorescence measurable in vivo. A stepwise two-photon absorption with 800 nm photons is used, which more selectively excites melanin (dermatofluoroscopy). Our review summarizes the experimental results on melanin fluorescence of the four types of cutaneous pigment cells from healthy and malignant tissues. Outstanding is the finding that different types of melanocytes (i.e., melanocytes of common nevi, versus dysplastic nevi or versus melanoma cells) show characteristically different fluorescence spectra. The possibilities of using this melanin fluorescence for melanoma diagnosis are shown. Moreover, the uniform fluorescence spectra emitted by different melanoma subtypes are essential. Conclusions are drawn about the molecular processes in the melanosomes that determine fluorescence. Finally, experimental suggestions for further investigations are given.

A prospective, multi-centre, follow-up clinical study evaluating the safety and effectiveness of a 24mg/ml sodium hyaluronate soft tissue filler.

Highly concentrated hyaluronic acid dermal fillers commonly contain 20 mg/ml sodium hyaluronate. The soft tissue filler SF 24 contains 24 mg/ml sodium hyaluronate. It is a viscoelastic gel, which is moderately cross-linked and specifically designed to correct moderate to deep wrinkles and folds of facial skin.To evaluate the long-term safety and effectiveness of the SF 24 for facial augmentation.The primary endpoints were effectiveness and safety, which were measured by investigators' assessment of wrinkle/ fold/ defect severity and reaction severity, respectively. The Global Esthetic Improvement Scale (GAIS) evaluated secondary endpoints, such as patient and physician satisfaction. Data collection occurred at treatment date (day 0) and at each visit set at an interval of 21 days, 121 days, 213 days, and 395 days. A total of 74 individuals (3 male and 71 female) received treatment with SF 24 across five sites. The baseline value (2. 70) of wrinkle and fold severity was reduced to 1.22 directly after treatment and remained improved even after 273 days at 1.59. The improvements compared to baseline were all significant (p < .001). The injection-related reactions were mainly short-term (1-7 days), mild to moderate in severity, and resolved without intervention. SF 24 is safe and effective for facial volume augmentation. It shows long-lasting (9 months) results in treated patients.

Dermatofluoroscopy diagnostics in different pigmented skin lesions: Strengths and weaknesses.

BACKGROUND: The melanin fluorescence of skin lesions is measurable with two-photon excitation, a process termed dermatofluoroscopy, which has shown a shift from the green spectra in benign melanocytic lesions to the red spectra in melanoma. This study addressed the question as to which kind of pigmented lesions can be correctly diagnosed as melanin-bearing malignant tumors. METHODS: 476 pigmented lesions including 101 cutaneous melanomas were analyzed with dermatofluoroscopy, measuring the melanin fluorescence in a grid-like fashion with a separation of measurement points of 0.2 mm. The results of the dermatofluoroscopy are presented as a diagnostic score with a cut-off score of ≥ 28 for the diagnosis of melanin-bearing malignant tumors, and were compared to the gold standard of histopathology. RESULTS: A highly significant difference (p < 0.0001) between the diagnostic scores of different skin tumors was found. Dermatofluoroscopy scores showed the highest sensitivity for melanomas (92.1 %). Interestingly, most pigmented basal cell carcinomas (BCCs, 88.9 %) were diagnosed as melanin-bearing malignant tumors. A higher sensitivity for the correct diagnosis was observed in older patients (≥ 53 years, p = 0.003), in patients with skin tanning (p = 0.025), and in patients with freckles during childhood (p = 0.046). CONCLUSIONS: Two-photon fluorescence is an innovative technique for the diagnosis of pigmented skin lesions, and shows a high sensitivity for detection of melanomas and pigmented BCCs.

The role of IL-17, IL-23 and IL-31, IL-33 in allergic skin diseases.

PURPOSE OF REVIEW: Allergic skin diseases such as urticaria, atopic dermatitis and allergic contact dermatitis are among the most common skin diseases with severe socioeconomic consequences. The pathogenesis of allergic skin diseases is complex. This review provides an overview of cytocines IL-17, IL-23, IL-31 and IL-33. RECENT FINDINGS: Current research results show a variety of immunological processes in the pathogenesis of the allergic skin diseases, including the role of cytokines. In addition to the Th1 and Th2 immune response, the immune response via Th17 is becoming increasingly important in allergic skin diseases but also the cytokines IL-23, IL-31 and IL-33 have been discussed in the literature recently. Different cytokines promote in a kind of orchestra the different symptoms seen in the different allergic skin diseases, including pruritus, dermatitis, mast cell mediator release and inflammation. SUMMARY: We are still in the early stages of understanding pathophysiology of allergic skin diseases and the role of various cytokines in the immune system. With the development of targeted antibodies against the proinflammatory cytokines, the variety of normal therapeutic options can be expected to evolve.

Dermatofluoroscopy Is Also for Redheads a Sensitive Method of Early Melanoma Detection.

BACKGROUND: Caucasians with red hair and fair skin have a remarkably increased risk of malignant melanoma compared to non-redhead Caucasians. OBJECTIVES: With the aim of a reliable melanoma diagnosis in redheads, the application of dermatofluoroscopy was analyzed in 16 patients with red hair. Most of them had been included in a clinical dermatofluoroscopy study for patients with the suspicion of melanoma. We examined whether the 25 lesions of the redheads showed the same characteristic melanin fluorescence spectra for dysplastic nevi and melanomas as those of non-redhead Caucasians or whether there was a different fluorescence pattern. This is important in view of the known significantly altered ratio of eumelanin to pheomelanin in the skin of redheads. METHODS: More than 8,000 spatially resolved fluorescence spectra of 25 pigmented lesions were measured and analysed. The spectra were excited by the stepwise absorption of two 800-nm photons (principle of dermatofluoroscopy). Furthermore, the fluorescence spectra of eumelanin and pheomelanin in hair samples were determined in the same way. RESULTS: The evaluation revealed that the melanin fluorescence spectra of dysplastic nevi and melanomas of redheads have the same spectral characteristics as those of non-redhead Caucasians. An accompanying result is that dermatofluoroscopy shows identical fluorescence spectra for eumelanin and pheomelanin. CONCLUSIONS: Dermatofluoroscopy proves to be a reliable diagnostic method also for redheads. Our results also explain our recent finding that there is a uniform fluorescence spectroscopic fingerprint for melanomas of all subtypes, which is of particular interest for hypomelanotic and apparently amelanotic melanomas containing pheomelanin.

Nonprescription acne vulgaris treatments: Their role in our treatment armamentarium-An international panel discussion.

BACKGROUND: Acne vulgaris (acne), a common inflammatory skin disorder, has its peak incidence between 14 and 19 years of age, with girls frequently developing acne earlier than boys. Over recent years, persistent acne is becoming more prevalent in adult women. OBJECTIVES: This review and panel discussion addresses challenges in acne management, particularly in adult women. The role which nonprescription acne treatment can play is explored when used as monotherapy or as an adjunctive treatment for acne of all severity. METHODS: The best available evidence on nonprescription acne treatment was coupled with the opinion of an international expert panel of dermatologists to adopt statements and recommendations discussed in this review. RESULTS: All severity of acne has a significant burden on patients. Addressing environmental factors that are important for the individual with acne may help to educate, prevent, effectively manage, and maintain acne, as per the panel. They agreed that the adult female acne population has unique needs because of their aging skin and social environment. Nonprescription acne treatment products may help to balance the efficacy and tolerability of prescription acne treatment. Currently, there are no specific guidelines for how to use nonprescription acne treatment products in these patients. CONCLUSION: The panel agreed that guidelines including nonprescription acne treatment either as monotherapy for mild acne or in combination with prescription treatments for more severe acne would address a significant unmet need.

Wound Healing Process After Thermomechanical Skin Ablation.

BACKGROUND AND OBJECTIVES: Energy-based devices have been widely applied for skin ablation. A novel ablation technique based on thermomechanical principles (Tixel© ) has been recently developed. The aim of this study was to examine the wound-healing process and clinical aspects after thermomechanical skin ablation. STUDY DESIGN/MATERIALS AND METHODS: Six female participants were treated with Tixel© on healthy skin of the dorsal side of the right forearm in a single session with a 600 µm protrusion and 12 milliseconds pulse. The treated area was examined with confocal laser scanning microscopy on day 1, 2, 7, and 14 after treatment. Clinical symptoms were evaluated at the same time-points. RESULTS: All patients developed erythema and mild edema on the treated areas, which completely disappeared within 14 days. No post-inflammatory hyperpigmentation or scarring was observed. Thermomechanical skin ablation resulted in the formation of homogeneous micro-ablation zones. Two weeks after ablation, the honeycomb patterns of the epidermis in all examined layers was thoroughly restored. Thus, wound-healing was completed. CONCLUSIONS: Wound healing after thermomechanical skin ablation is much faster compared with other fractionated ablation methods. Treatment intervals of 2-4 weeks could be recommended. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

Patient acceptance and trust in automated computer-assisted diagnosis of melanoma with dermatofluoroscopy.

BACKGROUND AND OBJECTIVES: Automated computer-guided diagnostic procedures are increasingly being integrated into patient care. However, in contrast to the increasing application of automation, patient acceptance and trust in such technologies has rarely been studied. Automated diagnosis of melanoma with dermatofluoroscopy was recently approved by regulatory agencies. The objective of this study is to assess patient acceptance and trust in automated melanoma diagnosis with dermatofluoroscopy. PATIENTS AND METHODS: We examined 140 pigmented skin lesions with dermatofluoroscopy as part of a prospective clinical study. Four weeks after their examination with dermatofluoroscopy, we contacted 100 patients with a 10-item questionnaire addressing their acceptance and trust in this technology on a five-point visual analogue scale. RESULTS: A "high" to "very high" level of patient acceptance and trust in dermatofluoroscopy was found in 74 % of responders. Most patients agreed that computer-assisted diagnoses are trustworthy and may generally improve the diagnostic performance of physicians. However, all responders insisted on the interpretation of computer-assisted diagnoses by a physician and frequently rejected the idea of computers completely replacing physicians. CONCLUSION: Patient acceptance and trust in dermatofluoroscopy was high. Patients clearly supported the use of automated, computer-assisted diagnostics as an adjunct to the physicians' examination.

MI (2-methyl-4-isothiazolin-3-one) contained in detergents is not detectable in machine washed textiles.

BACKGROUND: European legislation has banned the preservative methylisothiazolinone (MI) from inclusion in leave-on cosmetics. However, the risk for allergic reactions depends on exposure. The aim of this study was to determine the risk of MI in laundry detergents for household machine washing. METHODS: Different formulations of laundry detergents with commercial MI levels, up to one thousand ppm were used and three different types of clothes were washed in a normal household machine setting one time and 10 times. The level of MI was measured by HPLC. RESULTS: While MI could be retrieved in the positive control of clothes drenched with washing powder but not washed afterwards, MI could not be detected in any specimen of clothes washed under household conditions. The detection limit was 0.5 ppm. CONCLUSION: It is important to discuss the difference of risk and hazard. While MI clearly is a high hazard as a strong contact allergen, the risk depends on exposure. Regarding the risk of exposure levels for the consumer to MI in clothes it can be stated that the use of MI in laundry detergents is safe for the consumer if these products are used according to the instructions in the normal household setting machine wash.

A case report of combination treatment with potassium-titanyl phosphate laser and brimonidine topical gel in erythematotelangiectatic rosacea.

Laser therapies have been shown to provide symptom improvement in patients with erythema and telangiectasia of rosacea; however, they are associated with side effects such as erythema. Combinatorial treatment with pharmacological agents and laser have demonstrated better efficacy, fewer side effects and continued long-term remission compared with monotherapies. A case of moderate facial erythema that responded well to combination treatment with brimonidine 3 mg/g gel and a treatment course of potassium-titanyl phosphate (KTP) laser therapy is presented, showing a reduction from baseline, maintained after final laser session, by applying brimonidine 3 mg/g gel daily. Using brimonidine 3 mg/g gel to target post-laser treatment erythema is highly effective in minimising refractory erythema. Continued use of brimonidine 3 mg/g gel provides a sustained reduction of erythema, increasing the visibility of other signs and symptoms of rosacea that may be present. This can facilitate the treatment of these additional signs and symptoms.

Study protocol for a prospective, non-controlled, multicentre clinical study to evaluate the diagnostic accuracy of a stepwise two-photon excited melanin fluorescence in pigmented lesions suspicious for melanoma (FLIMMA study).

INTRODUCTION: Non-invasive, nanosecond, stepwise two-photon laser excitation of skin tissue was shown to induce melanin fluorescence spectra that allow for the differentiation of melanocytic nevi from cutaneous melanoma. METHODS AND ANALYSIS: This prospective, non-controlled, multicentre clinical study is performed to evaluate the diagnostic performance of the stepwise two-photon excited melanin fluorescence in the detection of cutaneous melanoma. The comparator will be the histopathological diagnosis. A total of 620 pigmented skin lesions suspicious for melanoma and intended for excision will be enrolled. ETHICS AND DISSEMINATION: Ethics approval was provided by the local ethics committees of the medical faculties of the University of Tuebingen, Heidelberg and Berlin. STUDY REGISTRATION: The FLIMMA study NCT02425475.

Physikalische Methoden zur Behandlung der Rosazea.

Die Rosazea ist durch vielfältige vaskuläre Veränderungen gekennzeichnet. Neben Teleangiektasien und Erythemen treten häufig auch sogenannte "Flushings" auf. Haupteinsatzgebiete von Licht- und Lasersystemen sind diese vaskulären Veränderungen, wie Erytheme und Teleangiektasien. Neben dem KTP-Laser, dem Farbstofflaser (PDL) und dem Nd:YAG-Laser kommen auch Blitzlampen (IPL) zum Einsatz. Neben der Rückbildung der vaskulären Komponente, ist auch eine Verbesserung der papulopustulösen Komponente beschrieben. Während der KTP-Laser sehr gute Ergebnisse bei Teleangiektasien zeigt, werden der Farbstofflaser und die Blitzlampen bevorzugt bei flächigen Erythemen eingesetzt. Der ND:YAG-Laser kann bei Teleangiektasien und Erythemen eingesetzt werden, birgt aber von allen Systemen das nicht einschätzbare Narbenbildungsrisiko in sich. Die Bildung von Phymen stellt eine klinische Ausprägung der Rosazea dar. Das am häufigsten vorkommende ist das Rhinophym. Bei moderaten und schweren Formen steht die Abtragung im Vordergrund. Die klassische chirurgische Abtragung stellt eine Möglichkeit zur Behandlung dar, häufig kommt es hierbei jedoch intraoperativ zu stärkeren Blutungen. Alternativmethode ist die Elektrochirurgie und die Dermabrasion, wobei bei beiden Methoden Narbenbildungen auftreten können. Neuere Methoden wie die CO2 -Laserabtragung, eventuell in Kombination mit der Erbium:YAG-Abtragung, stellen sichere und komplikationsärmere Varianten dar.

Physical modalities for the treatment of rosacea.

Rosacea is characterised by a wide variety of vascular changes. Apart from telangiectasia and erythema, often so-called flushing occurs. These vascular abnormalities can be targeted with specific light and laser devices. In addition to KTP laser, pulsed dye laser (PDL) and Nd:YAG laser, also intense pulsed light devices (IPLs) are used. The described therapeutic effects include the reduction of vascular abnormalities and even improvement of papulopustular changes. While the KTP laser shows very good results in telangiectasia, the dye laser and IPL devices are used preferably in erythema. The Nd:YAG laser is also a possibility for patients with telangiectasia and erythema. However, compared to the other laser and light devices the Nd:YAG laser carries the highest risk of unpredictable scarring. Phymatous changes are another clinical manifestation of rosacea, mostly affecting the nose (rhinophyma). Moderate and severe cases are commonly treated with ablation modalities. Traditional surgery is a treatment option, but is often associated with major intraoperative bleeding. Alternative methods include electrosurgery and dermabrasion, although both methods can cause scarring. Newer methods such as CO2 laser ablation, possibly in combination with the erbium:YAG laser, are safe alternatives with a lower risk of complications.

A novel thermo-mechanical system enhanced transdermal delivery of hydrophilic active agents by fractional ablation.

The Tixel is a novel device based on a thermo-mechanical ablation technology that combines a sophisticated motion and a temperature control. The fractional technology is used to transfer a very precise thermal energy to the skin thereby creating an array of microchannels, accompanying by no signs of pain or inconvenience. This study aimed to evaluate the effect of the Tixel on the skin permeability of three hydrophilic molecular models: verapamil hydrochloride, diclofenac sodium, and magnesium ascorbyl phosphate. Tixel's gold-platted stainless steel tip heated to a temperature of 400°C was applied on skin for 8ms or 9ms at a protrusion of 400µm (the distance in which the tip protrudes beyond the distance gauge). The experiments were carried out partly in vivo in humans using a fluorescent dye and a confocal microscopy and partly in vitro using porcine skin and a Franz diffusion cell system. The results obtained in this study have shown that (a) no significant collateral damage to the skin tissue and no necrosis or dermal coagulation have been noted, (b) the microchannels remained open and endured for at least 6h, and (c) the skin permeability of hydrophilic molecules, which poorly penetrate the lipophilic stratum corneum barrier, was significantly enhanced by using Tixel's pretreatment.

A systematic review of the role of interleukin-17 and the interleukin-20 family in inflammatory allergic skin diseases.

PURPOSE OF REVIEW: Allergic skin diseases include atopic dermatitis/eczema, contact dermatitis, and drug hypersensitivity. Allergic skin diseases have a high prevalence. Atopic dermatitis is one of the most common inflammatory skin diseases and similar for allergic rhinitis and allergic asthma. Over a long period, allergic diseases have been regarded as immunoglobulin E-mediated T-helper-2 (Th2)-driven. But new cytokines and T cells have been discovered within the last years. In this systematic review, the focus is laid on interleukin-17 (IL-17) and the interleukin-20 (IL-20) family which appear to be fine-tuning the Th2-driven answer. RECENT FINDINGS: IL-17 is a proinflammatory cytokine, which is produced by T cells. Primarily, IL-17 is produced by activated CD4+ cells, called Th-17 cells. IL-17 regulates keratinocyte expression of adhesion molecules and chemokines. IL-17 is involved in the pathogenesis of inflammatory diseases as psoriasis, arthritis, and inflammatory bowel diseases. In allergic diseases, the involvement of the TH17/IL17-pathway has only been recently described. Regarding the IL-20 family, IL-22 is the most interesting and the most studied cytokine in terms of allergic inflammatory disorders. IL-22 is produced by T-helper 22 cells, a new subset of CD4+ cells. SUMMARY: IL-17 as well as IL-22 seem to play a role in the pathogenesis of allergic skin diseases.

Prospective evaluation of supportive care with or without CVD chemotherapy as a second-line treatment in advanced melanoma by patient's choice: a multicentre Dermatologic Cooperative Oncology Group trial.

This prospective, nonrandomized multicentre, phase III study compared best supportive care (BSC) alone with cisplatin, vindesine and dacabazine-based (CVD) chemotherapy and BSC in patients with advanced melanoma. A total of 117 pretreated patients with metastatic melanoma were evaluated, 34 patients in arm A (BSC) and 83 in arm B (BSC and CVD). Primary endpoint was overall survival and secondary endpoints were disease control rate and quality of life (European Organisation for Research and Treatment of Cancer QLQ-C30). Owing to sparse recruitment of patients for randomization, the protocol has been changed based on patients' choice. Baseline characteristics were imbalanced with respect to the Karnofsky Performance Index (P=0.001), the existence of brain metastases (P=0.035) and earlier application of chemoimmunotherapy (P=0.038). Disease control was observed in 8.8% of patients in arm A and in 28.9% of patients in arm B (P=0.028). Median overall survival time was 137 days in arm A and 229 days in arm B (P=0.014). Multivariate analyses could not ascribe this prognostic benefit to CVD treatment. No significant difference in the quality of life could be found. This study could not detect clear survival benefits for polychemotherapy with CVD compared with BSC alone in patients with advanced metastatic melanoma. Interestingly, having the choice of chemotherapy or BSC alone in a second-line situation, more than 70% of patients chose polychemotherapy.