MMP1, MMP9, MMP11 and MMP13 in melanoma and its metastasis - key points in understanding the mechanisms and celerity of tumor dissemination.

BACKGROUND: Matrix metalloproteinase (MMP)1, MMP9, MMP11, and MMP13 are overexpressed in malignant melanoma (MM), being associated with tumor invasive phase, metastases, and more aggressive neoplastic phenotypes. AIM: The main objective of the current study was to correlate the expression of the MMPs with the evolution of MM toward distant metastasis. PATIENTS, MATERIALS AND METHODS: We designed a retrospective cohort study, including 13 patients with metastatic MM. Data concerning age, sex, localization of the primary lesion and metastasis, and histological and immunohistochemical features (intensity of expression and percent of positive cells for MMPs) were statistically processed. RESULTS: The time between the diagnosis of primitive melanoma and the diagnosis of metastasis ranged between 0 and 73 months, with a mean value of 18.3 months. The metastases rich in MMP1- and MMP9-positive cells occurred earlier than the metastases with low levels of positive cells. The mean period until metastasis was shorter for the MMP1-expressing tumors than the ones without MMP1 expression. MMP13 expression in the tumor and its metastasis was significantly linked with the time until the metastasis occurrence. CONCLUSIONS: This study emphasizes the roles of MMP1, MMP9, and MMP13 in the process of metastasis in melanoma and the opportunity to use them as therapeutic targets and surveillance molecules.

Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis.

This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.

Non-Invasive Techniques for Evaluating Alopecia Areata.

Alopecia areata (AA) is a disease affecting mostly young patients, being the second most prevalent cause of alopecia. For the assessment of AA patients, numerous non-invasive techniques are available. For diagnosing and treating AA, non-invasive hair follicle exploration is crucial. Trichoscopy, videodermoscopy, pull test, global scalp photography and scalp imaging techniques (reflectance confocal microscopy (RCM), multiphoton microscopy (MPM), and high-frequency ultrasonography (HF-USG) are non-invasive methods used to assess the hair loss. Short vellus hairs and yellow dots were the most commonly reported and sensitive trichoscopy signs of AA. Additionally, it was observed that AA activity was associated with black dots, micro-exclamation mark hairs and tapering hairs. A good prognosis of AA includes the transformation of vellus into terminal hairs. Reflectance confocal microscopy is a non-invasive imaging technique for in vivo evaluation of the skin and observation of cell morphology with a nearly histological resolution, which is helpful in diagnosis and management of AA. Additionally, MPM delivers information on hair follicles and scalp inflammation and can be utilized to assess hair growth while undergoing treatment. High-frequency ultrasonography allows distinguishing between hair cycle phases, which is undoubtedly important from the prognostic of AA. The current review aims to discuss the non-invasive methods of diagnosis of AA.

[Radiofrequency : Monopolar, bipolar, multipolar and fractional]. / Radiofrequenz : Mono-, bi- und multipolar sowie fraktional.

In addition to the laser technology, other physical methods are increasingly being used for medical and therefore medical cosmetic purposes. The most frequently used energy sources include the various application forms of radiofrequency (RF). The aim of the use of RF is to vaporize and coagulate tissue through a tissue temperature of >70 °C and to achieve a temperature of 42-44 °C especially in deeper layers, in order to promote a thermally induced collagen regeneration that enables skin tightening over the dermis. Unipolar, monopolar, bipolar, multipolar and fractional RF are suitable for medical applications. The result to be expected cannot compete with surgical lifting but RF is effective in cases of moderately sagging skin.

[High intensity focussed ultrasound for skin tightening]. / Hochintensiver fokussierter Ultraschall zur Hautstraffung.

High intensity microfocussed ultrasound (HIFU) is currently used for skin tightening and recently also for fat reduction. The HIFU uses bundled ultrasound waves that are focussed by a type of concave mirror to bundle thermal energy. The indications for HIFU include, in particular, sagging skin that does not need a plastic surgical operation for tightening. In most cases only one or two treatment sessions are needed. More expensive HIFU treatment can be further optimized by maintenance therapy with radiofrequency (RF). The greatest disadvantage of HIFU is that the treatment is very painful.

[Microfocussed vs. macrofocussed ultrasound for body contouring]. / Mikro- versus makrofokussierter Ultraschall zum Bodycontouring.

Focussed ultrasound is capable of heating tissue in small microscopic areas up to 65-70 °C and is a technique that can be used not only for destruction of superficial tissue but also for fat reduction. The focussing of sound waves according to the principle of a bundling of rays is carried out without injury to the skin. The penetration depth of the coagulation depends on the wavelength. Wavelengths that reach penetration depths of 6mm, 9mm and even 13mm and therefore deeper layers of the dermis and fat tissue are new. These enable fat cells to be eliminated and ultimately lead to girth reduction and also additionally to tightening. The effectiveness has been confirmed by several studies.

[The most common benign cutaneous neoplasms of the epidermis and appendages and their treatment]. / Häufigste gutartige Hauttumoren der Epidermis, ihrer Adnexe und deren Behandlung.

Benign cutaneous neoplasms are well defined histologically with absence of all of the following features: architectural disorder, necrosis, cytologic atypia, and atypical mitotic figures. The clinical appearance of any neoplasm is a very important diagnostic factor. The classification of the lesion determines the therapeutic options. This article summarizes the clinical aspects and treatments of the most common benign tumors of the epidermis and its appendages.

[The most common benign cutaneous neoplasms of vascular, muscular, and adipose tissue and their treatment]. / Häufigste benigne Gefäß­, Muskel- und Fettgewebstumoren der Haut und ihre Therapie.

Benign cutaneous vascular and cutaneous neoplasms arising from muscle or adipose tissue are rare. Their definition and classification are still controversially discussed. Histopathological and immunohistochemical studies, together with the new genetic tests, contribute significantly to the correct description of the various benign neoplasms of cutaneous origin. Clarifying whether a lesion is benign is fundamental for prognosis and therapeutic management. In most cases, surgical excision is the treatment of choice. Dermatologists should be familiar with the classifications of the most common benign cutaneous neoplasms of vascular, muscular, and adipose tissue and be able to recommend the procedures currently used for an accurate diagnosis. Ensuring that a lesion is benign and a good surgical outcome are essential for the patient.

[Benign skin neoplasms in children]. / Gutartige Hauttumoren bei Kindern.

There are many different types of skin neoplasms in children and most are benign. Dermatologists should be able to differentiate between the various types of benign skin neoplasms and be able to recommend optimal treatment to concerned patients. Surgical removal of benign skin neoplasms is often the only treatment option. The aim of this paper is to provide a general overview of epidermal lesions (e.g., inflammatory linear verrucous epidermal nevus [ILVEN], nevus sebaceous), tumors of the epidermal appendages (e.g. pilomatrixoma), cutaneous neoplasms (e.g. angiofibroma), fibromatoses (e.g., knuckle pads), tumors comprised of fat, muscle, or bone tissue (e.g., osteoma cutis, subungual exostosis), epidermal cysts and pseudocysts, and pathologic fibrosis reactions after dermal injury (keloid). Scientific data are scarce and only in the last decade has it been possible to perform histopathological examinations and genetic studies together with detailed phenotyping to gain new understanding of the pathogenetic mechanisms.

[Syndroms associated with benign skin tumors]. / Gutartige nichtmelanozytäre Hauttumoren bei Syndromen.

Benign skin tumors represent a wide category of diseases. The diagnosis is usually provided by the clinical aspect and the patient history. The pathological examination is not always considered necessary and in most cases the treatment is removal of the lesion by cryotherapy, electrosurgery or laser ablation. Deep phenotyping, including genetic and epigenetic findings, provided the basis of a new understanding of the pathogenetic mechanisms. Some benign skin tumors can be part of syndromes and the dermatologist should be aware of the extracutaneous associations defining these rare disorders: epidermal nevus can be associated with vascular malformations; nevus sebaceous can be associated with cerebral, ocular, and skeletal defects; nevus Becker is associated with cerebral, ocular, and skeletal defects; pilomatricomas appear earlier than colorectal cancer in Gardner's syndrome; tuberous sclerosis complex can associate not only central nervous system lesions but also pulmonary, cardiac or renal manifestations.

Assessment of Treatment Approaches and Outcomes in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Insights From a Pan-European Multicenter Study.

IMPORTANCE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug reactions associated with a high rate of mortality and morbidity. There is no consensus on the treatment strategy. OBJECTIVE: To explore treatment approaches across Europe and outcomes associated with the SJS/TEN disease course, as well as risk factors and culprit drugs. DESIGN, SETTING, AND PARTICIPANTS: A retrospective pan-European multicenter cohort study including 13 referral centers belonging to the ToxiTEN ERN-skin subgroup was conducted. A total of 212 adults with SJS/TEN were included between January 1, 2015, and December 31, 2019, and data were collected from a follow-up period of 6 weeks. MAIN OUTCOMES AND MEASURES: Risk factors for severe acute-phase complications (acute kidney failure, septicemia, and need for mechanical ventilation) and mortality 6 weeks following admission were evaluated using a multivariable-adjusted logistic regression model. One tool used in evaluation of severity was the Score of Toxic Epidermal Necrolysis (SCORTEN), which ranges from 0 to 7, with 7 the highest level of severity. RESULTS: Of 212 patients (134 of 211 [63.7%] women; mean [SD] age, 51.0 [19.3] years), the mean (SD) body surface area detachment was 27% (32.8%). In 176 (83.0%) patients, a culprit drug was identified. Antibiotics (21.2%), followed by anticonvulsants (18.9%), nonsteroidal anti-inflammatory drugs (11.8%), allopurinol (11.3%), and sulfonamides (10.4%), were the most common suspected agents. Treatment approaches ranged from best supportive care only (38.2%) to systemic glucocorticoids (35.4%), intravenous immunoglobulins (23.6%), cyclosporine (10.4%), and antitumor necrosis factor agents (3.3%). Most patients (63.7%) developed severe acute-phase complications. The 6-week mortality rate was 20.8%. Maximal body surface area detachment (≥30%) was found to be independently associated with severe acute-phase complications (fully adjusted odds ratio [OR], 2.49; 95% CI, 1.21-5.12; P = .01) and SCORTEN greater than or equal to 2 was significantly associated with mortality (fully adjusted OR, 10.30; 95% CI, 3.82-27.78; P < .001). Cyclosporine was associated with a higher frequency of greater than or equal to 20% increase in body surface area detachment in the acute phase (adjusted OR, 3.44; 95% CI, 1.12-10.52; P = .03) and an increased risk of infections (adjusted OR, 7.16; 95% CI, 1.52-33.74; P = .01). Systemic glucocorticoids and intravenous immunoglobulins were associated with a decreased risk of infections (adjusted OR, 0.40; 95% CI, 0.18-0.88; P = .02). No significant difference in 6-week mortality was found between treatment groups. CONCLUSIONS AND RELEVANCE: This cohort study noted differences in treatment strategies for SJS/TEN in Europe; the findings suggest the need for prospective therapeutic studies to be conducted and registries to be developed.

Deep-learning approach in the study of skin lesions.

BACKGROUND: Medical technology is far from reaching its full potential. An area that is currently expanding is that of precision medicine. The aim of this article is to present an application of precision medicine-a deep-learning approach to computer-aided diagnosis in the field of dermatology. MATERIALS AND METHODS: The main dataset was proposed in the edition of the ISIC Challenge that took place in 2019 and included 25 331 dermoscopic images from eight different categories of lesions-three of them were malignant and five benign. The behavior of the model was also tested on a dataset collected from the second Department of Dermatology, of the Colentina Clinical Hospital. RESULTS: The overall accuracy of the model was 78.11%. Of the total 5031 samples included in the test subset, 3958 were correctly classified. The accuracy of the model on the clinical dataset is lower than that obtained in the first instance. CONCLUSION: The architecture of the model can be considered of general use, being able to be adapted in an optimal way for a wide range of classifications. The model has achieved performance within the expected limits but can be further improved by new methods.

Prevention of Hand Eczema among Nurse Apprentice (PREVEDERM): An Interventional Study.

BACKGROUND: Workers in the healthcare sector are at high risk of developing occupational hand eczema mainly due to frequent exposure to irritants and/or allergens. Amongst workers in healthcare, nurses are at higher risk of developing hand dermatitis. OBJECTIVES: To evaluate the effectiveness of a short educational intervention program in preventing occupational hand eczema in nurse apprentices, using two objective tools, namely TEWL and EH, and the HECSI score. METHODS: Data regarding professions, wet work exposure, activities performed during working hours, self-reported eczema were collected from 230 nurse students, divided in two study groups: the intervention and the control group (CG). The intervention group (IG) was given education about risks and proper skin care and was provided with cosmeceuticals to be used for skin care during hospital activity. The evaluation of skin properties was performed using questionnaires, HECSI score, measurement of transepidermal water loss (TEWL) and epidermal hydration (EH). RESULTS: A number of 139 apprentice nurses completed the study. Of those participants who completed the study, 19.1% from CG and 19.6% from IG reported, at T1, hand eczema in the last 3 months, while at T2 (3 months later), 59.52 % of the CG and only 11.34 % from the IG stated having eczema in the last 3 months. In the IG, results showed an improvement of CM with 17% and of TEWL with 16%, with only a 0.5% improvement of CM in CG and a marked impairment of TEWL by 33%. CONCLUSION: Hand eczema is a common occupational dermatosis affecting the medical staff, even during apprenticeship. Early preventive training programs are effective in reducing the burden of occupational contact dermatitis.

Benefits of fractional radiofrequency treatment in patients with atrophic acne scars - Literature review.

OBJECTIVE: Acne scars carry a huge physical and psychological impact on people. This article aims to evaluate the role of fractional radiotherapy in treatment of atrophic acne scars. The main objective includes providing an up-to-date review of existing literature, presenting the most significant studies conducted in this field. METHODS: In order to study the impact of fractional radiotherapy on the appearance of atrophic acne scars, we conducted a search on Pubmed using the keywords "fractional radiotherapy", combined with/or "acne", "atrophic acne scars" and "acne scars" and found 75 papers, from which we selected 39. RESULTS: There are several therapeutic approaches for the improvement of acne scars with variable results and possible side effects. Fractional radiofrequency system has been used widely in the last years, as it turned out to be an effective treatment method, either in combination with other modalities, or alone. CONCLUSION: There are no generalized clinical guidelines adopted to standardize atrophic acne scar treatment. The multiple therapeutic options available create a dilemma in choosing the proper method in order to enhance its efficacy and to minimize its risks. The accumulated experience in nonablative collagen stimulating devices like fractional radiofrequency has proven that thickening of interstitial fibers in the dermis is possible with a controlled thermal injury, without epidermal damage and development of side effects.

Primary Cutaneous CD30+ Anaplastic Large Cell Lymphoma: A Rare Association With Large Plaque Parapsoriasis.

Primary cutaneous CD30-positive lymphoproliferative disorders represent the second most common subgroup of cutaneous T-cell lymphomas and include lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma, and borderline lesions. Primary cutaneous anaplastic large cell lymphoma is characterized by the presence of solitary or localized nodules or tumors located on the extremities or the cephalic or cervical region. Large plaque parapsoriasis is a chronic inflammatory disorder that associates a high risk of progression to mycosis fungoides. We report a case of CD30+ primary cutaneous anaplastic large cell lymphoma in a patient with a long history of large plaque parapsoriasis.

Is Occupational Skin Cancer More Aggressive than Sporadic Skin Cancer?

Background: Non-melanoma skin cancer (NMSC) represents the most frequently diagnosed cancer in humans. Occupational solar UV radiation exposure is associated with a higher-risk of developing NMSC, but still Romania does not acknowledge this affliction as an occupational disease. The study aims to determine if occupationally-induced NMSC is associated with more aggressive clinical and histopathological features compared to sporadic NMSC. Material and methods: A retrospective, analytical, comparative study was conducted during 2017-2019 in a University Department of Dermato-venereology in Bucharest, Romania, with focus on patients presenting with NMSC who underwent surgical excision of lesions followed by histopathological examination, classified as outdoor or indoor workers. High-risk clinical and histopathological characteristics were analysed and correlated with outdoor UV exposure. Outcomes: The study included 51 consecutive patients diagnosed with NMSC, of which 25 outdoor workers (OW) and 26 controls as indoor workers with no occupational UV exposure background. OW presented with 21 BCC and four SCC, while controls with 22 BCC and four SCC. Males were predominant in both groups and most patients came from urban environment. The mean age value was lower for the OW group compared to controls. OW had a 4.66 times higher risk of developing NMSC with aggressive location and size χ² (1, N=51) = 6.246, p=0.013, OR=4.66 (95% CI: 1.34, 16.23) and a 24-fold risk of developing NMSC with clinically poorly defined margins χ² (1, N=51) = 21.697, p<0.001, OR=24.44 (95% CI: 5.38,110.92). The risk of developing a high-risk histopathological subtype was 15 times greater for OW χ² (1, N=51) = 13.814, p<0.001, OR=15.27 (95% CI: 2.94,79.08). Moderate to severe desmoplastic reaction was 8.57 more frequent in controls χ² (1, N=51) = 12.244, p=0.001, OR=8.57 (95% CI: 2.42, 30.30). Grades 2 and 3 of actinic elastosis were significantly associated with outdoor work (χ² (1, N=51) = 33.382, p<0.001, OR=131.25 (95% CI: 13.60, 1266.37). The presence of ulceration and pigment association of tumors on the histopathological report were not significantly associated with outdoor working. Conclusion: 1. Occupational NMSC in Romania is associated with high-risk clinical features; 2. Poorly defined borders is a significant clinical high-risk factor associated with occupational UV exposure in NMSC; 3. High-risk histopathological subtypes are more frequently encountered in outdoor workers diagnosed with NMSC compared to indoor workers with no occupational UV exposure background; 4. Occupational NMSC is associated with significantly higher grades of desmoplastic reaction and of actinic elastosis compared to indoor workers.

Tophaceous Gout - When the Skin Comes First.

Gout represents a metabolic disorder with systemic echo, in which needle-like crystals of monosodium urate are deposited in various tissular structures. Crystals accumulation in the connective tissue (tophi) represents the late, chronic stage of this disease, usually emerging after an average of 10 years after disease onset. Herein we report three cases of patients aged 70, 33, and 53 who presented with painful subcutaneous nodules located on various body areas. All of them had hyperuricemia. Several conditions had to be investigated in order to establish the etiology of uric acid metabolism alterations. Laboratory and pathology findings established the diagnosis of gout, with tophi as the first symptom of the disease. Following patient education, diet and lifestyle changes, and medication, the outcome in all patients was favorable, with alleviation of the symptoms. Tophaceous gout as a first presentation of this disease is currently uncommon, but dermatologist should be aware of this rare finding for proper management of such cases and to prevent the resultant significant functional and quality of life impairment if not recognized early.

Exposure to solar UV radiation in outdoor construction workers using personal dosimetry.

Occupational exposure to solar UV radiation (SUVR), a Group 1 carcinogen according to the IARC classification is at high exposure levels in outdoor construction workers, usually above the suggested occupational limits. Furthermore, there are no regulations related to this exposure in the EU, except for the artificial UVR. Also, the use of the ICNIRP exposure guideline in an outdoor setting poses problems of adequate dose assessment. In this context, the main purpose of the study was to perform direct measurements of the SUVR dose in outdoor workers from the construction sector, using individual SUVR dosimeters (GENESIS-UV system), for a period of 7 months, from April to October, in a prospective, observational study in two groups of 10 outdoor workers in Romania, located at two different geographic sites. In term of cumulative standard erythema dose (SED), our study population of outdoor construction workers received high levels of solar UV radiation, ranging from 165 SED to 453 SED during 7 months of occupational activity, from April to October. Our results, ranging from 1.28 SED (standard erythema dose) per day to 6.4 SED per day pose an alarm signal to the national and European health authorities to take preventive action for outdoor workers, as the ICNIRP suggested limit value of 1.33 SED for mean daily erythemal UV exposure is vastly exceeded. We suggest that personal dosimetry for SUVR, from simple devices to complex systems as GENESIS-UV should be regularly and mandatory used in outdoor workers, similarly to the usage of personal dosimetry in occupational exposure to ionizing radiations, which could be included in European and national legislation to reduce both, the level of exposure and the detrimental effects on outdoor workers' health.

Traditional and ethnobotanical dermatology practices in Romania and other Eastern European countries.

The geographic and ecologic specificity of Romania and other Eastern European countries has resulted in the development of an exceptional diversity of medicinal plants. The purpose of this study was to provide an overview of the ethnobotanical dermatology practices based on the use of medicinal plants in this region. The indications, ethnopharmacologic activities, parts used, and administration of 106 medicinal plants are provided. We also discuss the relative importance of these species, using two modified indices of quantitative ethnobotany: Use Value Index and Relative Dermatologic Importance, which were calculated on the basis of etic constructions (indications and ethnopharmacologic activities). The species identified to have the highest dermatologic importance (on a scale of 100) were Brassica oleracea L. (100), Matricaria chamomilla L. (79.17), Arctium lappa L. (74.82), Daucus carota L. (72.28), Equisetum arvense L. (70.47), Juglans regia L. (69.93), Populous nigra L. (65.94), Symphytum officinale L. (63.59), Chelidonium majus L. (57.78), Calendula officinalis L. (57.78), Achillea millefolium L. (57.43), Melilotus officinalis L. (55.25), Allium cepa L. (51.45), Quercus robur L. (51.08), and Betula spp. (50.91). This preliminary study on ethnobotanical dermatology practices indicates that Eastern European traditional medical knowledge represents an important heritage that is currently underexploited.