The outcome in patients with BRAF-mutated metastatic melanoma treated with anti-programmed death receptor-1 monotherapy or targeted therapy in the real-world setting.

BACKGROUND: Immunotherapy and targeted therapy are currently two alternative backbones in the therapy of BRAF-mutated malignant melanoma. However, predictive biomarkers that would help with treatment selection are lacking. METHODS: This retrospective study investigated outcomes of anti-programmed death receptor-1 monotherapy and targeted therapy in the first-line setting in patients with metastatic BRAF-mutated melanoma, focusing on clinical and laboratory parameters associated with treatment outcome. RESULTS: Data from 174 patients were analysed. The median progression-free survival (PFS) was 17.0 months (95% CI; 8-39) and 12.5 months (95% CI; 9-14.2) for immunotherapy and targeted therapy, respectively. The 3-year PFS rate was 39% for immunotherapy and 25% for targeted therapy. The objective response rate was 72% and 51% for targeted therapy and immunotherapy. The median overall (OS) survival for immunotherapy has not been reached and was 23.6 months (95% CI; 16.1-38.2) for targeted therapy, with a 3-year survival rate of 63% and 40%, respectively. In a univariate analysis, age < 70 years, a higher number of metastatic sites, elevated serum LDH and a neutrophil-lymphocyte ratio above the cut-off value were associated with inferior PFS regardless of the therapy received, but only serum LDH level and the presence of lung metastases remained significant predictors of PFS in a multivariate analysis. CONCLUSIONS: Present real-world data document the high effectiveness of immunotherapy and targeted therapy. Although targeted therapy had higher response rates, immunotherapy improved PFS and OS. While the prognostic value of LDH was confirmed, the potential use of blood cell count-derived parameters to predict outcomes needs further investigation.

Selenium Disulfide-based shampoo applied for 4 weeks significantly improves dandruff and seborrheic dermatitis.

Seborrheic Dermatitis (SD) is a chronic and relapsing inflammatory condition accompanied by erythema, flaking and itching. Dandruff is a milder form of SD. Selenium disulfide (SeS2) is beneficial in both conditions. OBJECTIVES: to assess the efficacy of SeS2-based shampoo in dandruff/SD. MATERIALS & METHODS: an international, multicenter, observational study was conducted in 1407 adult subjects. SeS2- based shampoo was used 2 to 3 times per week for 4 weeks. Clinical efficacy criteria included improvement of hair, flaking, erythema and irritation on a scale from 0 to 5; investigator satisfaction was assessed at month 3 from 0 to 10. The subjects rated the impact of their hair problem (0 to 5), efficacy and satisfaction with SeS2-based shampoo at month 3. Tolerance was assessed throughout the study. RESULTS: At baseline, 68.2% had a flake severity score of 3-5, 49.9% an erythema severity score of 3-5, and 46.2% an irritation severity score of 3-5; 28.2% were bothered and 41.5% were very bothered. At study end, SD/D had at least clearly improved in 89.6% of subjects. All clinical signs had significantly (p<0.001) improved. 95.6% of subjects reported less pruritus. Significantly fewer (15.4%, p<0.0001) subjects were still bothered. The overall subject satisfaction score was 8.9±1.4; 97.6% of investigators were satisfied or very satisfied. Tolerance was good or very good in 98.8% of subjects. CONCLUSION: A SeS2-based shampoo applied 2 to 3 times per week is efficient and well tolerated in dandruff and SD.

Real-life experience in the effectiveness, impact on quality of life and safety of dupilumab treatment in patients with moderate to severe atopic dermatitis in the Czech Republic.

OBJECTIVES: The aim of the study was to assess the effectiveness and safety of dupilumab therapy in patients with moderate-to-severe atopic dermatitis (AD) in a real-life Czech bicentric cohort. METHODS: We retrospectively analysed 50 patients with moderate-to-severe AD treated with dupilumab in two centres in the Czech Republic. Baseline characteristics, the Eczema Area and Severity Index (EASI) score and Dermatology Life Quality Index (DLQI) were collected at baseline and each 3 following months. The proportion of patients achieving EASI50, EASI75, EASI90 and EASI100 were analysed. Levels of immunoglobulin E (IgE) were collected before and after 6 and 12 months of therapy. Adverse events were recorded as well. RESULTS: Thirty-two men and 18 women with mean body mass index (BMI) of 25.7 were enrolled in our analysis. The mean age of the patients was 37.6 years and the mean time from diagnosis until the initiation of dupilumab therapy was 35.0 years. After 4 months, EASI75 was achieved by 75.7%, out of which 40.5% achieved EASI90 and 10.8% achieved complete clearance. Improvement continued with time, and the proportion of patients with EASI90 increased to 71.4% at the 6th month and at the 12th month of therapy the EASI90 was 65.2%. EASI100 was achieved by 14.3% and 13.0% at the 6th and 12th month, respectively. A marked reduction was observed in the DLQI and also in IgE levels. EASI responses were independent of BMI. No new safety issues were identified. Adverse events were experienced by 44% (22/50) of the patients and they were all mild in intensity. Conjunctivitis and herpes simplex virus infection were the most common adverse events. CONCLUSION: Our results confirmed the effectiveness and safety of dupilumab in a real-life setting in adult patients with moderate-to-severe AD in the Czech Republic. Dupilumab was well-tolerated and resulted in a significant clinical improvement in combination with improvement of quality of life.

Risankizumab for the Treatment of Moderate-to-Severe Psoriasis: Real-Life Multicenter Experience from the Czech Republic.

INTRODUCTION: Risankizumab has been approved for the treatment of moderate-to-severe plaque psoriasis; however, real-life data are limited. Our objectives were to evaluate the effectiveness and safety of risankizumab and its impact on the quality of life of patients with psoriasis in a real-world setting. METHODS: We retrospectively analyzed 154 patients from 18 centers in the Czech Republic who had undergone biologic therapy with risankizumab for moderate-to-severe plaque psoriasis. Baseline characteristics included data on comorbidities, demographics, previous therapies, Dermatology Life Quality Index (DLQI) score, and Psoriasis Area and Severity Index (PASI) score. The proportion of patients achieving a 90% improvement in their PASI score from baseline (PASI 90) and complete resolution (PASI 100) after 16, 28, and 52 weeks was analyzed. RESULTS: A total of 95 men and 59 women with mean body mass index (BMI) of 29.6 were enrolled in our analysis. The mean age of the patients was 48.5 years and the mean time from diagnosis until initiation of risankizumab therapy was 22.5 years. After 16 weeks, 63.8 and 44.7% patients achieved PASI 90 and PASI 100 responses, respectively. Improvement continued with time, and the proportion of patients with PASI 90 and PASI 100 responses increased to 82.4 and 67.6%, respectively, at week 52. A significant reduction was observed over time in the DLQI. Patients achieving PASI 100 response at week 16 had a higher reduction in the DLQI score than those with PASI 90 response (- 15.9 vs. - 11.8). PASI 90 and PASI 100 responses were independent of the BMI and previous biologic therapy. No new safety issues were identified. CONCLUSIONS: In this patient population, risankizumab was effective and safe in a real-world setting, and a high number of patients achieved PASI 90 and PASI 100 responses. A higher reduction in the DLQI was seen in patients with PASI 100 response, which supports the evidence that this value should be the new therapeutic goal.

Silver distribution in chronic wounds and the healing dynamics of chronic wounds treated with dressings containing silver and octenidine.

Although silver is an efficient antimicrobial and is a widely used antiseptic in wound healing, previous studies have reported the cytotoxic in vitro effects of silver dressings. Moreover, few studies have addressed the distribution of silver in chronic wounds. The study compares the healing of chronic wounds treated with a standard-of-care silver dressing (Ag-CMC) and a dressing containing antiseptic octenidine (OCT-HA). Biopsies were taken from two wound areas before the commencement of treatment (baseline), after 2 weeks and after 6 weeks (the end of the study). We analyzed the histopathologic wound-healing score, silver distribution, and expression of selected genes. The wound-healing score improved significantly in the wounded area treated with OCT-HA after 2 weeks compared to the baseline and the Ag-CMC. The Ag-CMC wound areas improved after 6 weeks compared to the baseline. Moreover, collagen maturation and decreases in the granulocyte and macrophage counts were faster in the OCT-HA parts. Treatment with OCT-HA resulted in less wound slough. The silver, visualized via autometallography, penetrated approximately 2 mm into the wound tissue and associated around capillaries and ECM fibers, and was detected in phagocytes. The metallothionein gene expression was elevated in the Ag-CMC wound parts. This exploratory study determined the penetration of silver into human chronic wounds and changes in the distribution thereof during treatment. We observed that silver directly affects the cells in the wound and elevates the metallothionein gene expression. Octenidine and hyaluronan dressings provide a suitable alternative to silver and carboxymethyl cellulose dressings without supplying silver to the wound.

Inequalities in the patterns of dermoscopy use and training across Europe: conclusions of the Eurodermoscopy pan-European survey.

BACKGROUND: Dermoscopy is a widely used technique, recommended in clinical practice guidelines worldwide for the early diagnosis of skin cancers. Intra-European disparities are reported for early detection and prognosis of skin cancers, however, no information exists about regional variation in patterns of dermoscopy use across Europe. OBJECTIVE: To evaluate the regional differences in patterns of dermoscopy use and training among European dermatologists. MATERIALS & METHODS: An online survey of European-registered dermatologists regarding dermoscopy training, practice and attitudes was established. Answers from Eastern (EE) versus Western European (WE) countries were compared and their correlation with their respective countries' gross domestic product/capita (GDPc) and total and government health expenditure/capita (THEc and GHEc) was analysed. RESULTS: We received 4,049 responses from 14 WE countries and 3,431 from 18 EE countries. A higher proportion of WE respondents reported dermoscopy use (98% vs. 77%, p<0.001) and training during residency (43% vs. 32%) or anytime (96.5% vs. 87.6%) (p<0.001) compared to EE respondents. The main obstacles in dermoscopy use were poor access to dermoscopy equipment in EE and a lack of confidence in one's skills in WE. GDPc, THEc and GHEc correlated with rate of dermoscopy use and dermoscopy training during residency (Spearman rho: 0.5-0.7, p<0.05), and inversely with availability of dermoscopy equipment. CONCLUSION: The rates and patterns of dermoscopy use vary significantly between Western and Eastern Europe, on a background of economic inequality. Regionally adapted interventions to increase access to dermoscopy equipment and training might enhance the use of this technique towards improving the early detection of skin cancers.

Long-term impact of adalimumab therapy on biomarkers of systemic inflammation in psoriasis: Results of a 2 year study.

Psoriasis patients are at increased risk of atherosclerosis, characterized by endothelial dysfunction, linked through systemic inflammation. Anti-TNF-a therapy seems to decrease this risk. The purpose of this study was to measure the levels of serum markers associated with systemic inflammation in psoriasis patients, compared to healthy individuals and to investigate the change in their levels after 3 months and 2 years of adalimumab therapy. We investigated four biomarkers: high-sensitivity C-reactive protein (hsCRP), oxidized low-density lipoproteins (OxLDL), E-selectin, and Interleukin 22 (IL-22). These markers were measured in healthy volunteers and in 28 patients with moderate/severe psoriasis before and after 3 and 24 months of treatment with adalimumab. Psoriasis patients had increased levels of markers in comparison to the control group. After 3 months of therapy, E-selectin decreased significantly (P < .001), as well as IL-22 (P < .001). hsCRP also decreased but did not show a statistical significance, OxLDL were slightly higher than initially. After 24 months, 17 patients were still being treated with adalimumab. In these patients, hsCRP (P < .05), E-selectin (P < .001) and IL-22 (P < .001) were significantly decreased. OxLDL remained at a higher level. The stable decrease of E-selectin, hsCRP, and IL-22 after 24 months confirms that adalimumab suppresses systemic inflammation.

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.

A Corrective Cosmetic Improves the Quality of Life and Skin Quality of Subjects with Facial Blemishes Caused by Skin Disorders.

BACKGROUND: Facial blemishes resulting from skin disorders have a significant effect on the patient's self-esteem and impact quality of life (QOL). AIM: To assess the impact of a corrective cosmetic (CC) on QOL on top of skin quality parameters. METHODS: An international observational study was conducted on subjects with visible facial flaws that would benefit from a corrective cosmetic. Investigators collected data regarding demographics, QOL using the Skindex-16 scale, skin dryness and tautness, subject and investigator satisfaction, cosmetic acceptability and tolerance at baseline and after 4 to 6 weeks of daily use. RESULTS: A total of 1840 subjects participated; the mean age was 31.5±11.1 and 95% were women. Acne accounted for 48.9% of skin conditions, followed by melasma (16.7%) and rosacea (15.3%). Of the subjects 81.2% had at least 10% of the face affected and the condition was rated as disfiguring by 45.3% of the subjects; 45.0% and 44.4%, respectively, had neither taut nor dry skin at baseline. Baseline Skindex-16 scores for symptoms, emotions, functioning and overall were 1.4±1.3, 3.5±1.6, 2.4±1.8 and 2.4±1.3, respectively, on a scale from 0 to 6. Compliance was 96.0±10.6%. At the end of the study, Skindex-16 scores had significantly (p<0.0001) improved for all parameters, as did skin dryness and tautness. Subject and investigator satisfaction were high or very high; cosmetic acceptability was high or very high and local tolerance good or very good. CONCLUSION: The tested corrective cosmetic significantly improved the QOL of subjects with significant facial flaws, skin tautness and dryness, and was well tolerated.

[Sebaceous carcinoma in situ in extraocular skin : Case report and discussion of the new entity]. / Sebaziöses Carcinoma in situ der extraokulären Haut : Fallbericht und Diskussion eines neuen Entitätskonzepts.

Sebaceous carcinoma in situ (SCIS) is a rare intraepidermal neoplasia, mostly occurring on the eyelid and the face. Despite abundant literature on invasive sebaceous carcinoma, there are relatively few articles about SCIS. We report the case of 78-year-old woman suffering from SCIS of the left cheek, presenting as an erythematous skin lesion. The histological examination revealed intraepidermal and intraadnexal population of atypical cells with foamy cytoplasm and with immunohistochemical adipophilin-, cytokeratin-7- and EMA-positivity in the tumor cells.

Vichy mineralizing water with hyaluronic acid is effective and well tolerated as an adjunct to the management of various dermatoses and after esthetic procedures.

INTRODUCTION: M89, containing 89% of Vichy mineralizing water and hyaluronic acid, has been developed to reinforce the skin barrier and to improve skin quality. AIM: To assess efficacy and tolerability of M89. METHOD: Observational survey of subjects with facial dermatoses or after esthetic procedures. M89 served as adjunct to conventional therapy. Clinician assessments of erythema, desquamation, irritation and patient-reported dryness, burning, itching, and stinging/tingling were conducted at baseline and 4 weeks. At 1 week and 4 weeks, patient assessed tolerance and satisfaction with M89. RESULTS: A total of 1630 subjects participated; 92.5% were females. Mean age was 41.1 ± 11.3 years. Dermatological indications accounted for 32.5%, procedures for 67.5%. At 4 weeks, in subjects with dermatoses, erythema had resolved or improved in 68.0%, desquamation in 83.4%, and irritation in 93.3%. Dryness, burning, itching, and stinging/tingling scores had decreased by 63.8%, 81.8%, 70.9%, and 85.2%, respectively (all P ≤ .0001); 75.7% considered that their skin was sufficiently hydrated. In the procedure group, erythema had resolved or improved in 72.5%, desquamation in 75.2%, and irritation in 88.1%. Dryness, burning, itching, and stinging/tingling scores had decreased by 62.1%, 78.8%, 70.0%, and 84.2%, respectively (all P ≤ .0001); 74.1% considered that their skin was sufficiently hydrated. Almost all subjects reported soothed skin and satisfaction with product texture. Subject and investigator satisfaction was very high. CONCLUSION: M89 significantly improves skin signs and symptoms after 4 weeks of continued use with no tolerance issues in subjects with dermatological indications. Moreover, subjects who have had recently undergone esthetic procedures M89 allowed a satisfying skin recovery.