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BACKGROUND The SARS-CoV-2 pandemic has generated immense healthcare pressure, forcing critical decisions to be made in a socially alarmed environment. Adverse conditions have led to acute stress reactions, affective pathologies, and psychosomatic reactions among health personnel, which has been exacerbated by the successive waves of the pandemic. The recovery of the entire health system and its professionals has been hindered, making it essential to increase their resilience. OBJECTIVE This study aimed to analyze the coping strategies employed by healthcare workers in Ecuador during the COVID-19 pandemic, and to create a multimedia tool to enhance the well-being of health professionals. METHODS The "BE+ Against COVID-19" experience from Spain was transferred to Ecuador, where 6 focus groups of healthcare professionals were conducted to collect information on institutional and personal coping strategies. RESULTS The information collected from the actions carried out by the Ecuadorian healthcare workers was categorized into 4 types of coping strategies. A new audiovisual tool consisting of a series of PODCASTs was designed based on this study to spread these strategies globally in the Spanish-speaking world. CONCLUSIONS The recovery of professionals to be prepared in the event of a possible new outbreak is crucial to ensure quality and patient safety. Interventions like this provide a way to obtain lessons learned and generate new tools for health professionals. CLINICALTRIAL Institutional approval was given for the development of focus groups (2022-0080-M).

Background: There are severaltherapeutic options for infantile haemangiomas (IH). Propranolol is used according to a pivotal trial. We aimed to describe the characteristics of IH in clinical practice, including the therapies used, and to compare the characteristics of patients treated with propranolol with those of the trial to assess its external validity. Methods: Consecutive patients attending 12 Spanish hospitals from June 2016 to October 2019 were included (n = 601). Results: The mean age was 3.9 (SD:1.9) months, with a 2:1 female-to-male ratio. Most IHs were localized (82%, 495), superficial (64%, 383) and located in the face (25%, 157) and trunk (31%, 188). Median size was 17 (IR: 10-30) x 12 (IR: 7-20) mm. Complications were found in 16 (3%) patients. Treatment was initiated for 52% (311). Most patients received timolol (76%, 237); propranolol was reserved for complications or high-risk IHs. Aesthetic impairment was the main reason for starting therapy (64%, 199). Several characteristics of the patients and IHs treated with propranolol are similar to those of the pivotal clinical trial, but 1/3 of IHs did not reach the minimum diameter to meet the inclusion criteria, and important prognostic information was not reported. Conclusions: As most patients receive treatment for aesthetic impairment, there is a need to better understand the aesthetic results of therapies and to increase evidence on the use of timolol, which is currently the most common therapy. Propranolol is being used in a population generally similar to that of the trial; however, this statement cannot be definitely confirmed. Yes Introducción: Existen diversas opciones terapéuticas para los hemangiomas infantiles (HI). El propranolol se utiliza con base en un ensayo pivotal. Nuestro objetivo fue describir las aracterísticas del HI en la práctica clínica, incluyendo las terapias utilizadas, así como com parar las características de los pacientes tratados con propranolol y las de los pacientes del ensayo, para valorar su validez externa. Métodos: Se incluyó consecutivamente a los pacientes que acudieron a doce hospitales espanoles ˜ desde junio de 2016 a octubre de 2019 (n = 601). Resultados: La edad media fue de 3,9 (DE:1,9) meses, con una ratio mujer-varón de 2:1. La mayoría de los HI fueron de tipo localizado (82%, 495), superficial (64%, 383) y ubicados en cara (25%, 157) y tronco (31%, 188). El tamano˜ mediano fue de 17 (RI: 10-30) x 12 (RI: 7-20) mm. Se encontraron complicaciones en 16 (3%) pacientes. Se inició tratamiento en el 52% (311) de los casos. La mayoría de los pacientes recibió timolol (76%, 237), reservándose propranolol para las complicaciones o los HI de alto riesgo. El compromiso estético fue el principal motivo de iniciar la terapia (64%, 199). Las diversas características de los pacientes y de los HI tratados con propranolol fueron similares a las del ensayo clínico pivotal, aunque 1/3 de los HI no alcanzó el diámetro mínimo para cumplir los criterios de inclusión, y no se comunicó información pronóstica importante. Conclusiones: Dado que muchos pacientes reciben tratamiento debido al compromiso estético, existe una necesidad de conocer mejor los resultados estéticos de las terapias e incrementar la evidencia sobre el uso de timolol, que actualmente es la terapia más común. El propranolol está siendo utilizado en una población generalmente similar a la del ensayo; sin embargo, esta afirmación no puede confirmarse de manera definitiva.

Failure to follow do-not-do recommendations (also known as low-value practices) is one of the causes of the lack of quality care in all health systems in all countries. Healthcare professionals must be provided with information about these low-value practices that are still frequently performed and their implications for patients and the healthcare system. Continuous education is a key factor in this scenario, so that health students, health professionals, and even patients are kept updated with the main do-not-do recommendations. Gamified platforms are one of the most valuable options for continuous education, as they combine learning efficiency with a high level of engagement for the students. Besides, the effectiveness of gamification platforms can be improved by adding artificial intelligence techniques. In this paper, a novel gamified platform focused on improving knowledge about low-value practices is proposed. AI techniques, as well as NLP tools are used to optimize the effectiveness of learning by adapting the platform to each user, at an individual level. Besides, the engagement of students is encouraged by their participation in a common project, namely the creation of a specialized dictionary for do-not-do terms. Hardware development is currently in progress. A basic gamification platform has already been developed for the two main mobile operating systems. Developing IA and NLP techniques to analyse the training outputs and make the platform adaptable to each student is progressing. The proposed learning tool can significantly improve healthcare quality and be applied to many other learning fields, particularly when continuous training is required.

IntroductionEvidence shows that gender has a substantial impact on health behaviours, access to and use of health systems and health system responses. This study aims to assess gender bias in patients subjected to low-value practices in the primary care setting and to develop recommendations for reducing adverse events that women experience for this reason.Methods and analysisA Delphi study will be performed to reach a consensus on the ‘Do Not Do’ recommendations with a possible gender bias. A retrospective cohort study in a random selection of medical records will then be carried out to identify the frequency of adverse events that occur when the selected ‘Do Not Do’ recommendations are ignored. Qualitative research techniques (consensus conference and nominal group) will be carried out to develop recommendations to address any gender bias detected, considering barriers and facilitators in clinical practice.Ethics and disseminationThe study was approved by the ethics committee of San Juan de Alicante Hospital (San Juan de Alicante, Spain) Reference N. 21/061. We will disseminate the research findings via peer-reviewed articles, presentations at national and international scientific forums and webinars.Trial registration numberThe study was registered at ClinicalTrials.gov (NCT05233852) on 10 February 2022.

The development of persistent subcutaneous nodules at vaccination or hyposensitization injection site is a rare and under-reported event. These lesions have been attributed to the aluminium salts used as adjuvants. Patch testing on patients with the aforementioned clinical manifestations have yielded high sensitization rates to aluminium. It is believed this delayed hypersensitivity is the apparent cause of these reactive lesions in the dermis and subcutaneous tissue. In addition, aluminium hypersensitivity may cause contact dermatitis and gingivitis since it can be found in toothpaste and deodorants. We describe a series of 4 patients who developed SN at the injection site of vaccines and/or hyposensitization therapy, who underwent ultrasonography and patch testing for diagnostic confirmation. Patient management usually consists of potent topical steroids, antihistaminics, emollients and aluminium-containing products avoidance.

Digital, This study analyzed the frequency and intensity of acute stress among health professionals caring for COVID-19 patients in four Latin American Spanish-speaking countries during the outbreak. A cross-sectional study involved a non-probability sample of healthcare professionals in four Latin American countries. Participants from each country were invited using a platform and mobile application designed for this study. Hospital and primary care workers from diferent services caring for COVID-19 patients were included. The EASE Scale (SARS-CoV-2 Emotional Overload Scale, in Spanish named Escala Auto-aplicada de Sobrecarga Emocional) was a previously validated measure of acute stress. EASE scores were described overall by age, sex, work area, and experience of being ill with COVID-19. Using the Mann–Whitney U test, the EASE scores were compared according to the most critical moments of the pandemic. Univariate and multivariate analysis was performed to investigate associations between these factors and the outcome ‘acute stress’. Finally, the Kruskal–Wallis was used to compare EASE scores and the experience of being ill. A total of 1372 professionals responded to all the items in the EASE scale: 375 (27.3%) Argentines, 365 (26.6%) Colombians, 345 (25.1%) Chileans, 209 (15.2%) Ecuadorians, and 78 (5.7%) from other countries. 27% of providers sufered middle-higher acute stress due to the outbreak. Worse results were observed in moments of peak incidence of cases (14.3 ± 5.3 vs. 6.9 ± 1.7, p < 0.05). Higher scores were found in professionals in COVID-19 critical care (13 ± 1.2) than those in non-COVID-19 areas (10.7 ± 1.9) (p = 0.03). Distress was higher among professionals who were COVID-19 patients (11.7± 1) or had doubts about their potential infection (12 ± 1.2) compared to those not infected (9.5 ± 0.7) (p = 0.001). Around one-third of the professionals experienced acute stress, increasing in intensity as the incidence of COVID-19 increased and as they became infected or in doubt whether they were infected. EASE scale Could be a valuable asset for monitoring acute stress levels among health professionals in Latin America. ClinicalTrials: NCT04486404., Ciencias Médicas y de la Salud

Background Mitogen-activated protein kinase inhibitors (MEKi) are currently used for the treatment of central nervous system tumors in children and have shown promising results. Cutaneous adverse effects are among the most common toxicities described in adults, but few studies exist in pediatric patients. Objective We aimed to describe the cutaneous adverse effects associated with MEKi in pediatric patients. Methods A retrospective study was carried out at our pediatric hospital in Barcelona, Spain, in patients undergoing treatment with MEKi. Results Sixty-one children between 1 and 18 years of age were included. All patients developed cutaneous toxicity. Eczema, hair abnormalities, oral aphthae, and paronychia were among the most common cutaneous side effects. Conclusions Recognizing skin toxicity in pediatric patients under treatment with MEKi is essential to establishing appropriate education and therapy, thereby improving treatment tolerability and minimizing avoidable interruptions in treatment.

BACKGROUND Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast-flow vascular malformations (FFVMs) in one-third of patients. Few case series have been described, and none in Spain. AIM To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM-AVM. METHODS We conducted an observational study of patients with CM-AVM syndrome diagnosed in 15 Spanish hospitals over 3 years. The main clinical, radiological, genetic findings and associated diseases were analysed. RESULTS In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the 'herald patch'. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas. CONCLUSIONS Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype-phenotype correlation.

Current efforts to find specific genodermatoses treatments and define precise pathogenesis mechanisms require appropriate surrogate models with human cells. Although transgenic and gene knockout mouse models for several of these disorders exist, they often fail to faithfully replicate the clinical and histopathological features of the human skin condition. We have established a highly efficient method for precise deletion of critical gene sequences in primary human keratinocytes, based on CRISPR-Cas9-mediated gene editing. Using this methodology, in the present study we generated a model of Netherton syndrome by disruption of SPINK5. Gene-edited cells showed absence of LEKTI expression and were able to recapitulate a hyperkeratotic phenotype with most of the molecular hallmarks of Netherton syndrome, after grafting to immunodeficient mice and in organotypic cultures. To validate the model as a platform for therapeutic intervention, we tested an ex vivo gene therapy approach using a lentiviral vector expressing SPINK5. Re-expression of SPINK5 in an immortalized clone of SPINK5-knockout keratinocytes was capable of reverting from Netherton syndrome to a normal skin phenotype in vivo and in vitro. Our results demonstrate the feasibility of modeling genodermatoses, such as Netherton syndrome, by efficiently disrupting the causative gene to better understand its pathogenesis and to develop novel therapeutic approaches., Graphical Abstract, Exploiting the advantages of their highly efficient CRISPR-Cas9 gene editing strategy, in this study, Gálvez et al. abrogate SPINK5, the Netherton syndrome-causing gene, in primary human keratinocytes. SPINK5-knockout cells show disease hallmarks in vitro and in vivo, enabling the development of trustworthy models suitable for the evaluation of advanced therapies for genodermatoses.

Background: Keratinocytic epidermal naevi (KENs) are congenital benign skin mosaic lesions that share common mutations with some subsets of urothelial carcinomas. Moreover, several patients with extensive KEN who also developed urothelial carcinomas at young ages have been reported. Thus, patients with extensive KEN may harbour mosaic urothelial oncogenic mutations that would favour the early development of urothelial carcinomas. Methods: We selected five patients with extensive KEN involving the lower part of the back and performed a molecular characterisation of urothelial and cutaneous samples using a next-generation sequencing (NGS) custom panel targeting candidate oncogenic genes. Results: Mosaic pathogenic mutations were detected in KEN in all patients. In four out of five patients, mosaic pathogenic mutations in FGFR2 or HRAS were also detected in samples from the urothelial tract. Moreover, we report a patient who developed urothelial carcinomas at age 29 and harboured an HRAS G12S mutation both in skin and urothelial tumour samples. Conclusions: We conclude that patients with extensive KEN involving the lower part of the back frequently harbour oncogenic mutations in the urothelium that may induce the development of carcinomas. NGS panels can be considered as highly sensitive tools to identify this subgroup of patients, which might permit adoption of screening measures to detect malignant transformation at early stages.

BACKGROUND: Oral propranolol accelerates the involution of infantile haemangiomas (IHs). However, it is not clear whether IHs treated with oral propranolol are associated with fewer sequelae than when left untreated. OBJECTIVES: To quantify and describe sequelae associated with IHs treated with oral propranolol, and to explore whether treated IHs are associated with fewer sequelae than untreated IHs. MATERIALS & METHODS: This multicentre, retrospective, cohort study included patients with IH treated with oral propranolol =2 mg/kg for at least six months, with photographic images available at baseline and at age 4-5 years. A historical comparison cohort comprised 185 patients with untreated IHs. Main outcomes/measures were: IH features, treatment characteristics and type/degree of sequelae. RESULTS: Oral propranolol, most commonly at 2 mg/kg/day (mean duration: nine months), was initiated in 171 patients (mean age: 6.02 months). After treatment, 125 of 171 (73.1%) IHs were associated with no/minimal sequelae. The most common sequelae were telangiectasia (78%), fibrofatty tissue (37%) and anetodermic skin (28%). Deep IHs were associated with significantly fewer sequelae than other subtypes. Ulceration appeared to increase the likelihood of severe sequelae. IHs with a stepped border was associated with more severe sequelae than those with a progressive border (44% versus 27%, p < 0.05). Treated IHs resolved without sequelae or were associated with a sequela that did not need correction in 27.7% more cases than untreated IHs (RR: 1.61; p < 0.001). CONCLUSION: Among IHs treated with oral propranolol, 73% resolved without, or were associated with minimal sequelae. Deep IHs were associated fewer sequelae than other subtypes. Oral propranolol decreased the likelihood of IH sequelae requiring correction.