New developments in sunscreens

Topical sunscreen application is one of the most important photoprotection tool to prevent sun damaging effects in human skin at the short and long term. Although its efficacy and cosmeticity have significantly improved in recent years, a better understanding of the biological and clinical effects of longer wavelength radiation, such as long ultraviolet A (UVA I) and blue light, has driven scientists and companies to search for effective and safe filters and substances to protect against these newly identified forms of radiation. New technologies have sought to imbue sunscreen with novel properties, such as the reduction of calorific radiation. Cutaneous penetration by sunscreens can also be reduced using hydrogels or nanocrystals that envelop the filters, or by binding filters to nanocarriers such as alginate microparticles, cyclodextrins, and methacrylate polymers. Finally, researchers have looked to nature as a source of healthier products, such as plant products (e.g., mycosporines, scytonemin, and various flavonoids) and even fungal and bacterial melanin, which could potentially be used as substitutes or enhancers of current filters

Vitiligo-like lesions located over In-transit metastases of malignant melanoma as a clinical marker of complete response to pembrolizumab.

Anti-programmed cell death (PD)-1 therapies in metastatic tumors have a high incidence of immune adverse events, including cutaneous manifestations such as vitiligo-like lesions. This side effect is associated with increased survival and it is a clinical marker of response to treatment. This case report is a graphic representation of the appearance of vitiligo-like lesions over in-transit metastases of malignant melanoma linked to a complete response to treatment with pembrolizumab

Diferencias en la angiogénesis de los carcinomas cutáneos de células basales y escamosas

Introducción: la angiogénesis del tumor se ha reconocido como un importante indicador de la progresión. El objetivo de este estudio es analizar si existe una posible asociación entre la angiogénesis en Carcinomas Basocelulares (CBC) y Espinocelulares (CEC) con su comportamiento clínico. Material y métodos: se evaluó la angiogénesis en los tejidos tumorales de 35 CCB y 42 CCE de la piel, mediante una tinción inmunohistoquímica con CD 31 y CD 105 y se recuentan los vasos con el método visual de Chalkley además han revisado las historias clínicas valorando datos clínico-demográficos. Resultados: en el CCE se pueden observar vasos en el núcleo tumoral, por el contrario no se observó ninguno en la cohorte de CCB (p <0,05). No se observaron puntos calientes en cualquiera de los dos tipos de tumor. El conteo de Chalkley en el CCE superó al conteo de CCB para ambos marcadores endoteliales (CD31 para p = 0,001 y para CD105 p <0,01). La presencia de microvasos en el cuerpo del carcinoma de células escamosas no se correlaciona con un peor pronóstico y con recurrencia, a diferencia de otras publicaciones. En contraste con otros estudios no se observaron diferencias en los niveles de expresión entre CD31 y CD105. Conclusiones: la demostración de que la densidad de vasos en el CCB es significativamente menor que en las CCE, al menos podría explicar en parte el lento crecimiento de CCB y la reducción de su potencial metastásico. En nuestro estudio CD105, considerado en la literatura como un marcador específico para los vasos neoformados, no mostró diferencia significativa con CD31

Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality. Objective The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT. Material and methods Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated. Results The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p&lt;0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94–159.8) Conclusion Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapyThis project received support from the Instituto de Salud Carlos III and Fondos Feder Europeos, MINECO (FIS PI15/00974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Modeling an optimal 3D Skin-on-Chip within microfluidic devices for pharmacological studies

Preclinical research remains hampered by an inadequate representation of human tissue environments which results in inaccurate predictions of a drug candidate''s effects and target''s suitability. While human 2D and 3D cell cultures and organoids have been extensively improved to mimic the precise structure and function of human tissues, major challenges persist since only few of these models adequately represent the complexity of human tissues. The development of skin-on-chip technology has allowed the transition from static 3D cultures to dynamic 3D cultures resembling human physiology. The integration of vasculature, immune system, or the resident microbiome in the next generation of SoC, with continuous detection of changes in metabolism, would potentially overcome the current limitations, providing reliable and robust results and mimicking the complex human skin. This review aims to provide an overview of the biological skin constituents and mechanical requirements that should be incorporated in a human skin-on-chip, permitting pharmacological, toxicological, and cosmetic tests closer to reality

Risankizumab for the treatment of moderate to severe psoriasis: impact on health-related quality of life and psychological wellbeing

Biologic treatments are increasingly being used in the management of moderate to severe plaque psoriasis (PSO). Risankizumab (RZB) is a humanized monoclonal antibody that specifically blocks the p19 subunit of interleukin 23, which in turn regulates the activation, differentiation, and survival of Th17. RZB has proved their efficacy and their safety compared to anti-TNF. However, studies that assess and compare the improvement in other secondary PROs such as the patient's quality of life are still scarce. Health-related quality of life (HRQoL) is the sum of physical health, well-being, and participation; it defines the functional effect of a disease or its treatment and how it is perceived by the patient. The objective of this paper is to analyze the literature on the impact of treatment with RZB on the quality of life of patients with PSO and their psychological well-being. A bibliographic search was carried out to identify all the papers published from July 2015 to June 1, 2022, on RZB treatment in psoriasis and its impact on health-related quality of life and psychological well-being, finally twenty articles have been evaluated in full text, of which 8 were excluded because they did not meet the inclusion criteria. Risankizumab has shown not only to have very relevant data on effectiveness and safety, but all of this is associated with an improvement in quality of life related to health and psychological well-being measured on generic and specific quality of life scales, both in pivotal trials, ad hoc analysis, and data in real clinical practice

Resistencias del carcinoma basocelular a la terapia fotodinámica con metil-aminolevulinato

Introducción: la terapia fotodinámica (TFD) con metil-aminolevulinato (MAL), es uno de los tratamientos no invasivos más usados en el tratamiento del Carcinoma Basocelular (CBC). Sus principales ventajas son la alta tasa de respuestas completas, a los tres meses, del 91% y a los 5 años del 76% con un excelente resultado cosmético y una gran satisfacción por parte del paciente. Aunque las tasas de respuesta a la TFD son altas existen algunos CBCs que no responden adecuadamente. El estudio de las diferencias clínicas, histológicas y biológicas de los CBCs en su respuesta a la TFD nos ayudará a conocer mejor su mecanismo de acción, así como aumentar su eficacia y eficiencia permitiendo la selección de los pacientes.Material y métodos: estudio observacional con recopilación de datos de forma retrospectiva en el que se han utilizado lesiones de pacientes compatibles con CBC que fueron tratados con TFD con MAL en la Unidad de Dermatología del Hospital San Jorge de Huesca desde el 1 de Enero de 2006 al 31 de Diciembre de 2015. Hemos recogido variables demográficas (edad, sexo, localización del tumor, tamaño, fototipo, factores predisponentes), parámetros histológicos clásicos en aquellos que tenían biopsia previa y/o curetaje, siempre que hubiese material histológico suficiente, (espesor tumoral, estroma peritumoral, pérdida de empalizada periférica, pleomorfismo, ulceración, presencia del infiltrado linfocitario intratumoral, invasión perineural, así como la presencia de elastosis). A continuación, hemos realizado tinciones de P53, Ki-67, CD-31, COX2, EGFR, survivina y β-catenina. Posteriormente se ha evaluado la respuesta a TFD en las líneas celulares de cáncer de CBC de ratón, ASZ y células BSZ, ambas se aislaron de ratones heterocigotos para el gen Ptch+/- y las segundas carecen del gen P53.Resultados: se incluyeron en el estudio un total de 390 Carcinomas Basocelulares en 182 pacientes. La tasa de respuesta global fue de 82,8%, con un tiempo medio de seguimiento de 35,96 meses (DE=23,46), un mínimo de 3 meses y un máximo de 6 años. Las variables clínicas de los CBCs que se asocian con mala respuesta a la TFD con MAL son: la variante nodular, la localización en área H, edad más avanzada, los fototipos IV, V y VI de Fitzpatrick o los pacientes que han recibido un mayor número de sesiones. Se evaluó la histología de 63 casos de CBCs tratados con TFD con MAL, de estos 49 muestras pertenecían a CBCs respondedores y 14 a especímenes de CBCs no respondedores. En relación a las variables anatomo-patológicas, la presencia de infiltrado inflamatorio linfocítico peritumoral previo es un factor predictor de buena respuesta a la TFD con MAL. La inmunoreactividad positiva a P53 en CBC es un factor predictor de buena respuesta, por el contrario el patrón de tinción de β-catenina con refuerzo periférico de los islotes de células basaloides se asocia a resistencia del carcinoma basocelular a la TFD con MAL. La línea celular ASZ difiere de la línea celular BSZ en que expresa más P53 y al ser ambas líneas sometidas a tratamiento con TFD con MAL, la línea celular ASZ presenta una viabilidad menor que BSZ.Conclusiones: consideramos que hay evidencia suficiente para concluir que el subtipo histológico de CBC nodular frente a la variante superficial es un factor predictor de mala respuesta, sin embargo tener una edad inferior a 63 años, la inmunotinción positiva para P53 y la presencia de infiltrado inflamatorio linfocítico peritumoral son factores predictores de buena respuesta del CBC a la TFD con MAL.<br /

Fully home-based methyl aminolevulinate daylight photodynamic therapy for actinic keratosis of the face or scalp: A real life open study

Methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) is highly effi-cacious for the treatment of nonhyperkeratotic actinic keratosis (AK), even when par-tially performed at home. To evaluate the long-term effectiveness, safety, andpatient-reported outcomes of MAL DL-PDT performed completely by the patient inreal life conditions. An open prospective study was conducted in Spain amongpatients diagnosed with at least five AK lesions on the face or the scalp. Patientsreceived instruction and information in infographic format to perform MAL DL-PDTat home. All had been treated with 30% urea daily for 7 days before the day of MALDL-PDT. Meteorological conditions on the day of the treatment and adverse effectswere recorded. Patients underwent follow-up, and a second session of home-basedMAL DL-PDT if deemed necessary, 3, 6, and 12 months after the initial treatmentsession. The study population consisted of 22 patients (19 men and three women,mean [standard deviation, SD] age, 72.05 [6.96] years). A complete response wasobserved in 47.7% of AK lesions at 3 months (p< 0.001) and 65.9% (n=199) at12 months (p< 0.001). Olsen grade II lesions showed the highest rate of response(76.07% at 12 months). The mean (SD) actinic keratosis area and severity index scoredecreased significantly from 4.99 (2.43) at baseline to 2.33 (1.01) at 12 months(p=0.0234). Adverse effects were mild and expected. A majority of patients were“satisfied”or“very satisfied”with the treatment instruction provided (90.9%) andthe treatment outcome (72.7%). MAL DL-PDT can be applied at home like any othertopical treatment for AK. Our results indicate good long-term effectiveness, a highlevel of patient satisfaction, and no significant side effect