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Congenital epidermodysplasia verruciformis (CEV) is a Genodermatosis linked to different inheritance patterns and mutations of the EVER1/TMC6 and EVER2/TMC8 genes. There is an acquired form (AEV) associated with immunodeficiency states, including human immunodeficiency virus (HIV) infection; however, the literature about AEV is limited and imprecise, so a systematic review was performed. A search of the main databases from 1975 to 2021 identified 126 studies, of which 80 met the inclusion criteria. The diagnosis of AEV is complex due to atypical manifestations and locations, it requires a mean follow-up of 7 years, and the lesions do not change with ART therapy, CD4 count, or viral load. Histopathological findings are variable depending on the location of the lesions. HPV 5 remains the serotype most frequently associated with AEV and CEV, although HPV 20 is more frequent than HPV 8 in AEV. Most treatments have low efficacy, the most described are glycolic acid 15%, 5-fluorouracil 5%, imiquimod 5%, and topical retinoids all of them in monotherapy or combined with cryotherapy. Other alternatives include topical cidofovir and systemic retinoids with variable results. The oncologic prognosis is still inconclusive; however, the development of squamous cell carcinoma and melanoma are frankly lower concerning CEV. This review opens new opportunities for future research. Additionally, we provide clear and useful key points for the practice of dermatologists and all professionals treating HIV patients around the world.

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BACKGROUND: Novel and highly effective drugs for non-melanoma skin cancer (NMSC) improve patient outcomes, but their high cost strains healthcare systems. Spain's decentralized public health system, managed by 17 autonomous communities (AaCc), raises concerns about equitable access. METHODS: A cross-sectional survey (July-September 2023) was sent to Spanish Multidisciplinary Melanoma Group (GEM Group) members to assess access to new drugs. FINDINGS: Fifty physicians from 15 Spanish AaCc responded to the survey. Access for drug with approved public reimbursement, Hedgehog inhibitors in basal-cell carcinoma and anti PD-L1 antibody in Merkel carcinoma, was observed in 84% and 86% of centers, respectively. For other EMA-approved treatments, but without reimbursement in Spain access decreased to 78% of centers. Heterogeneity in access was mainly observed intra regions. CONCLUSION: Unequal financial support for drugs for NMSC with creates a patchwork of access across Spanish hospitals, with variations even within the same AaCc.

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Fundamento: como promedio se han generan tres millones de casos de cáncer de piel a nivel global en los últimos años. Esta situación ocurre entre otras razones por la constante exposición a la radiación solar y la no aplicación de fotoprotección. Objetivo: determinar la experiencia parental en fotoprotección durante la infancia. Método: se realizó un estudio etnográfico en la Unidad Educativa de la Parroquia San Juan del Cantón Riobamba, Provincia Chimborazo, durante el período de estudio de octubre 2022 a octubre 2023. Se realizaron 14 entrevistas a cuidadores de preescolares, los que fueron escogidos a través del muestreo no probabilístico. Se dispuso de dos técnicas de recolección de la información: el autorreportaje y la entrevista semiestructurada. Resultados: se describieron cada una de las categorías que emergieron en el estudio según el nivel de frecuencia: fotounidad, fotoexperiencia-conocimiento y fotosanidad. Se construyó un mapa representacional en el cual se determinó que la familia en sí representa la fotounidad, mediante la participación de todos sus miembros en la protección de los efectos nocivos del sol. La sombrilla que cubre a la familia refleja la fotoexperiencia-conocimiento adquiridos por los cuidadores, que actúan como protección al daño solar mediante medidas preventivas y de cuidado. El sol y sus rayos solares simbolizan la fotosanidad, que corresponde a la exposición a rayos solares y sus efectos nocivos para la salud. Conclusiones: la implementación de medidas de fotoprotección desde edades tempranas resulta de vital importancia para la prevención del cáncer de piel, por lo que es necesario brindarles a los padres información adecuada sobre los riesgos solares y las medidas preventivas.

Foundation: on average, three million cases of skin cancer have been generated globally in recent years. This situation occurs among other reasons due to constant exposure to solar radiation and non-application of photoprotection. Objective: determine parental experience in photoprotection during childhood. Method: an ethnographic study was carried out in the Educational Unit of the San Juan Parish of the Cantón Riobamba, Chimborazo Province, during the study period from October 2022 to October 2023. 14 interviews were carried out with preschool caregivers, who were chosen through of non-probabilistic sampling. Two information collection techniques were available: self-report and semi-structured interview. Results: each of the categories that emerged in the study were described according to the level of frequency: photounity, photoexperience-knowledge and photosanity. A representational map was constructed in which it was determined that the family itself represents photounity, through the participation of all its members in protecting themselves from the harmful effects of the sun. The umbrella that covers the family reflects the photo-experience-knowledge acquired by the caregivers, which act as protection from sun damage through preventive and care measures. The sun and its solar rays symbolize photosanity, which corresponds to exposure to sunlight and its harmful effects on health. Conclusions: the implementation of photoprotection measures from an early age is of vital importance for the prevention of skin cancer, so it is necessary to provide parents with adequate information about sun risks and preventive measure.

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AIM: Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD. METHODS: This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs). RESULTS: The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI: 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI: 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI: 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI: 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust. CONCLUSIONS: IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.

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Introduction: Squamous cell carcinoma (SCC) is a malignant neoplasm that accounts for approximately 15-25% and 70-80% of all feline cutaneous and oral tumors, respectively. Similar to that in humans, feline SCC can be highly invasive locally; however, its metastasis rate is low. Thus, effective local treatment may be curative for most patients, and includes surgery, electrochemotherapy (ECT), cryosurgery, or a combination of these. However, this neoplasia can manifest more aggressively in some patients, leading to higher recurrence rates. In humans, perineural invasion (PNI) has been described as a relevant tumor dissemination pathway associated with high-risk SCC, resulting in higher recurrence rates, resistance to local treatments, and short survival. However, PNI and its prognostic value have not been described in feline SCC. This study aimed to evaluate the PNI in a feline population with SCC treated with ECT and correlate its presence with the occurrence of local recurrence and other clinical variables. Methods: Twenty-four cats histopathologically diagnosed with SCC between 2013 and 2021 were retrospectively selected from the medical records of the Oncological Center Vet Cancer (São Paulo, SP, Brazil). The inclusion criteria were ECT as the sole therapy, histopathological evaluation of PNI, and absence of distant metastatic disease. Results: The complete response rate was 96% (23/24), and PNI was identified in 33% of the cats (8/24, PNI-positive group), whereas 67% were free of this invasion (16/24, PNI-negative group). All PNI-positive cats developed local recurrence, whereas only five PNI-negative cats experienced recurrence. Local recurrence was significantly associated with PNI (p = 0.03). Discussion: The results of this study are preliminary but promising. The data obtained are the first regarding PNI occurrence in feline SCC and pave the way for further studies, mainly to correlate the PNI with survival data and better define its prognostic value.

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Ibrutinib, a tyrosine kinase inhibitor with a broad spectrum of action, has been successfully explored to treat hematological and solid cancers. Herein, we investigated the anti-cancer effect of Ibrutinib on melanoma cell lines. Cytotoxicity was evaluated using the MTT assay. Apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) production, cell proliferation, and cell cycle stages were determined by flow cytometry. LDH release and Caspase 3/7 activity were determined by colorimetric and luminescent assays, respectively. Cell migration was evaluated by wound scratch assay. Gene expression was determined by real-time PCR. Gene Ontology (GO) enrichment analysis of melanoma clinical samples was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). MTT assays showed that Ibrutinib is toxic for MeWo, SK-MEL-28, and WM164 cells. The annexin V/PI staining, Caspase 3/7 activity, and LDH release in MeWo cells revealed that apoptosis is the primary mechanism of death caused by Ibrutinib. Corroborating such observation, we identified that Ibrutinib treatment impairs the mitochondrial membrane potential of such cells and significantly increases the transcriptional levels of the pro-apoptotic factors ATM, HRK, BAX, BAK, CASP3, and CASP8. Furthermore, Ibrutinib showed antimetastatic potential by inhibiting the migration of MeWo cells. Finally, we performed a functional enrichment analysis and identified that the differential expression of Ibrutinib-target molecules is associated with enrichment of apoptosis and necrosis pathways in melanoma samples. Taken together, our results clearly suggest that Ibrutinib can be successfully explored as an effective therapeutic approach for melanomas.

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Cutaneous melanoma (CM) poses a therapeutic challenge due to its aggressive nature and often limited response to conventional treatments. Exploring novel therapeutic targets is essential, and natural compounds have emerged as potential candidates. This study aimed to elucidate the impact of curcumin, a natural compound known for its anti-inflammatory, antioxidant, and anti-tumor properties, on metastatic melanoma cells, focusing on the purinergic system and immune responses. Human melanoma cell line SK-Mel-28 were exposed to different curcumin concentrations for either 6 or 24 h, after which we assessed components related to the purinergic system and the inflammatory cascade. Using RT-qPCR, we assessed the gene expression of CD39 and CD73 ectonucleotidases, as well as adenosine deaminase (ADA). Curcumin effectively downregulated CD39, CD73, and ADA gene expression. Flow cytometry analysis revealed that curcumin significantly reduced CD39 and CD73 protein expression at specific concentrations. Moreover, the A2A receptor's protein expression decreased across all concentrations. Enzymatic activity assays demonstrated that curcumin modulated CD39, CD73, and ADA activities, with effects dependent on concentration and duration of treatment. Extracellular ATP levels increased after 24 h of curcumin treatment, emphasizing its role in modulating hydrolytic activity. Curcumin also displayed anti-inflammatory properties by reducing NLRP3 gene expression and impacting the levels of key inflammatory cytokines. In conclusion, this study unveils the potential of curcumin as a promising adjuvant in CM treatment. Curcumin modulates the expression and activity of crucial components of the purinergic system and exhibits anti-inflammatory effects, indicating its potential therapeutic role in combating CM. These findings underscore curcumin's promise and warrant further investigation in preclinical and clinical settings for melanoma management.

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BACKGROUND: Timely diagnosis plays a critical role in determining melanoma prognosis, prompting the development of deep learning models to aid clinicians. Questions persist regarding the efficacy of clinical images alone or in conjunction with dermoscopy images for model training. This study aims to compare the classification performance for melanoma of three types of CNN models: those trained on clinical images, dermoscopy images, and a combination of paired clinical and dermoscopy images from the same lesion. MATERIALS AND METHODS: We divided 914 image pairs into training, validation, and test sets. Models were built using pre-trained Inception-ResNetV2 convolutional layers for feature extraction, followed by binary classification. Training comprised 20 models per CNN type using sets of random hyperparameters. Best models were chosen based on validation AUC-ROC. RESULTS: Significant AUC-ROC differences were found between clinical versus dermoscopy models (0.661 vs. 0.869, p < 0.001) and clinical versus clinical + dermoscopy models (0.661 vs. 0.822, p = 0.001). Significant sensitivity differences were found between clinical and dermoscopy models (0.513 vs. 0.799, p = 0.01), dermoscopy versus clinical + dermoscopy models (0.799 vs. 1.000, p = 0.02), and clinical versus clinical + dermoscopy models (0.513 vs. 1.000, p < 0.001). Significant specificity differences were found between dermoscopy versus clinical + dermoscopy models (0.800 vs. 0.288, p < 0.001) and clinical versus clinical + dermoscopy models (0.650 vs. 0.288, p < 0.001). CONCLUSION: CNN models trained on dermoscopy images outperformed those relying solely on clinical images under our study conditions. The potential advantages of incorporating paired clinical and dermoscopy images for CNN-based melanoma classification appear less clear based on our findings.

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PURPOSE: The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. METHODS: Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. RESULTS: There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. CONCLUSION: IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.

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