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.

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.

[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.

Deroofing followed by thorough sinus tract excision: a modified surgical approach for hidradenitis suppurativa.

BACKGROUND AND OBJECTIVES: Deroofing has proven to be an effective method to treat mild to moderate forms of hidradenitis suppurativa (HS). The basic procedure includes removal of the sinus roof, followed by secondary intention healing, while fibrotic tissue usually stays in situ. We have tried to establish a modified method of deroofing in which meticulous removal of the fibrotic tissue results in a low recurrence rate in moderate to severe HS patients. PATIENTS AND METHODS: An open prospective study consisted of 96 deroofed lesions in 52 consecutive patients with moderate to severe HS. Patients were followed up for a minimum of 28 months. RESULTS: Recurrence occurred after a median time of 2.3 months in 14 % of locations. Recurrences according to location were as follows: 6 % in the axillary region and 25 % in the inguinal region. Postoperative bleeding was the only considerable complication and occurred in 7 % of treated locations. Seven patients were lost to follow-up. CONCLUSION: Modified deroofing followed by meticulous sinus tract removal is a surgical approach suitable for patients with moderate disease, especially in the axillary region. This results in a low recurrence rate and the same healing period as that of the standard deroofing procedure.

Hypophysitis and other autoimmune complications related to immune checkpoints inhibitors´ treatment: Spectrum of imaging appearances.

OBJECTIVES: Immune checkpoints inhibitors (ICI) represent a new therapy option for the treatment of several advanced tumors. However, this therapy has been linked to a spectrum of ICI related autoimmune (AI) adverse events. Some may be life threatening and their diagnosis is tricky. The aim of our study was to describe various imaging appearances of ICI related secondary hypophysitis and other coincidental AI diseases. MATERIAL AND METHODS: We included 28 patients (19 females, 9 men, mean aged 58±13 years), who were consecutively treated mostly for advanced stage melanoma by different ICI. All their CT/MRI records and clinical data were reviewed. RESULTS: We found 5 (18%) cases of endocrinology proven secondary hypophysitis; 2 cases of panhypopituitarism and 3 cases of central hypocortisolism. Four cases were MRI positive, 1 case was MRI negative. Three cases were accompanied by other AI diseases: 1 by hemorrhagic colitis and mesenterial lymphadenitis, 1 by AI pancreatitis and 1 by pneumonitis. On MRI pituitary gland was swollen in 3 cases, twice enhanced non-homogenously, once homogenously; infundibular enlargement was present in 2 cases. Those 3 cases reacted to glucocorticoid therapy by hypophyseal shrinkage. In 1 case of MRI positive hypophysitis, the pituitary gland was not enlarged, slightly nonhomogeneous with peripheral contour enhancement; no reaction to glucocorticoids was mentioned. CONCLUSION: Secondary hypophysitis is probably more common ICI related adverse event than reported in the literature. Its MRI appearance is variable. Most of our cases were in coincidence with other AI ICI related events that affected their clinical manifestations.

Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists.

Background: Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking. Methods: Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge. Results: In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P = 0.19) and specificity to 75.7% (±11.7%, P < 0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P < 0.01) and level-II (75.7%, P < 0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P < 0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge. Conclusions: For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification. Clinical trial number: This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).

[Hidradenitis suppurativa - symptoms, diagnostics, and therapy]. / Hidradenitis suppurativa - symptomy, diagnostika a lécba.

Hidradenitis suppurativa is a chronic skin disorder characterized by recurrent inflammatory nodules, fistulas, abscesses, and scarring mainly in the intertriginous areas with terminal hair and apocrine glands. Hidradenitis suppurativa manifests usually after puberty, in the third life decade and persists for many years. The prevalence of the disease is estimated to be 0,5 % in the Czech Republic. Women are most often affected in the axillary and inguinal parts, while men in the perianal and gluteal areas. The exact pathogenesis is still unknown. It is assumed that hyperkeratosis of the hair follicle leads to its occlusion, dilatation and further rupture when keratin and bacteria are spilled into the dermis causing a massive inflammatory reaction. Smoking and obesity belong to the main triggering factors. Without therapy, the disease is chronic and progressive. The standard therapy depends on the extension of the disorder. For not extensive lesions, treatment consists of topical antiseptics, antibiotics or long- term therapy with systemic antibiotics. In more advanced stages, systemic therapy with TNF-α antagonists is needed. Further therapeutic modality is surgical intervention and wide excision of the affected area. Nevertheless, recurrences in the adjacent tissue cannot be avoided.

Impact of adalimumab treatment on cardiovascular risk biomarkers in psoriasis: Results of a pilot study.

Psoriasis is a chronic systemic immune-mediated inflammatory dermatosis associated with several comorbidities. Psoriasis patients are at increased risk of developing cardiovascular diseases (CVD), namely, coronary heart disease, stroke or peripheral vascular disease, and psoriasis seems to be an independent cardiovascular risk factor. Antipsoriatic systemic therapy, especially anti-tumor necrosis factor (TNF)-α, seems to exert a beneficial effect on these comorbidities. The purpose of this study was: (i) to measure the level of cardiovascular serum markers in psoriasis patients in comparison with healthy volunteers; and (ii) to compare the serum level of the same markers in patients before and 3 months after adalimumab therapy. We investigated six biomarkers connected to CVD: C-reactive protein (measured high sensitively, hsCRP), oxidized low-density lipoproteins (oxLDL), oxLDL/ß-glycoprotein I complex (oxLDL/ß2GPI), vascular endothelial adhesion molecule 1 (VCAM-1), E-selectin and interleukin (IL)-22. These biomarkers were measured in 21 patients with moderate/severe psoriasis before and after treatment with adalimumab and in healthy volunteers. hsCRP (P < 0.05), oxLDL-ß2GPI complex (P < 0.05), E-selectin (P < 0.001) and IL-22 (P < 0.001) were significantly increased in comparison with healthy controls, whereas oxLDL and VCAM-1 were also higher in psoriasis patients but the difference did not reach statistical significance. A decrease of E-selectin (P < 0.001) and IL-22 (P < 0.001) was observed after 3 months of adalimumab therapy. Inhibition of TNF-α seems to not only improve psoriasis but also decreases serum cardiovascular biomarkers. E-selectin and IL-22 could serve for monitoring of the efficacy of antipsoriatic systemic therapy on cardiovascular risk.

Malignant melanoma in the Czech Republic: incidence and mortality according to sex, age and disease stage.

BACKGROUND: The Czech Republic has reported one of the highest incidence rates of cutaneous melanoma (CM) in Europe and the rate continues to rise. Our study undertook a detailed investigation of the incidence and mortality of melanoma relative to sex, age and disease stage. The main goals were to elucidate the causes of the rising trends and explain the differences in development relative to sex, age and disease stage. METHODS AND RESULTS: The estimated annual percentage change (EAPC) using the Joinpoint Regression Model was calculated separately for men and women for all age categories and for all T stages of TNM classification. The EAPC for women was slightly higher than for men. This was only found in melanomas thinner than 1 mm (T1). For all other stages (T2, T3 and T4) the situation was worse in men. A higher incidence rate of CM and the higher value of EAPC were found for women in younger age categories (up to 49 years). In the next age category, from 50 to 59 years, the incidence of CM was comparable in both sexes as well as the EAPC. In the older age categories, i.e. 60 years and older, a significant increase was found predominantly in men. The mortality rates were only comparable between men and women in the 20 to 29 year age group. In all other categories there was a higher mortality for men. CONCLUSIONS: The number of melanoma cases in the Czech Republic is increasing faster than any other cancer. Despite improved survival rates, the death rate from CM continues to climb as a result of exponential increases in incidence. Thus primary and secondary prevention campaigns are essential for future reductions in CM incidence and mortality in the Czech Republic.

Light-activated nanofibre textiles exert antibacterial effects in the setting of chronic wound healing.

The maintenance of an aseptic environment for chronic wounds is one of the most challenging tasks in the wound-healing process. Furthermore, the emergence of antibiotic-resistant bacterial strains is on the rise, rendering conventional treatments less effective. A new antibacterial material consisting of a polyurethane Tecophilic(™) nanofibre textile (NT) that was prepared by electrospinning and doped by a tetraphenylporphyrin (TPP) photosensitizer activated by visible light was tested for use in wound beds and bandages. In vitro experiments were performed to assess the antibacterial activity of the textile against three bacterial strains. Furthermore, the new textile was tested in 162 patients with chronic leg ulcers. A complete inhibition of in vitro growth of the three tested bacterial strains was observed on the surface of NTs that had been illuminated with visible light and was clinically demonstrated in 89 patients with leg ulcers. The application of the textiles resulted in a 35% decrease in wound size, as assessed via computer-aided wound tracing. Wound-related pain, which was estimated using a visual analogue scale, was reduced by 71%. The results of this trial reveal that the photoinactivation of bacteria through the photosensitized generation of short-lived, highly reactive singlet oxygen O(2) ((1) Δ(g) ) results in relatively superficial antibacterial effects in comparison with standard antiseptic treatment options. Thus, such treatment does not interfere with the normal healing process. This method therefore represents a suitable alternative to the use of topical antibiotics and antiseptics and demonstrates potentially broad applications in medicine.