Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Exposure to UV Radiation in Lifeguards on Barcelona's Beaches: An Underestimated Occupational Risk. / [Artículo traducido] Exposición a radiación ultravioleta en socorristas de las playas de Barcelona: un riesgo laboral infravalorado.

BACKGROUND: The development of skin cancer is closely related to high exposure to UV radiation. Lifeguards are at an increased risk of excessive sun exposure. OBJECTIVES: The main objective of this study was to measure the exposure of Barcelona's beach lifeguards to UV radiation. METHODS: Measurements in the work chair were taken every 30min on a typical working day from 10:45 am to 19:15 pm. These measurements were carried out on four different days. These data were used to calculate the erythematous doses received during working hours, as well as those potentially received throughout the summer season. Vitamin D production was also estimated for the four days that the radiation received was measured, and the amount generated was calculated for the entire summer season. RESULTS: Exposure to UV radiation among Barcelona lifeguards far exceeds safety limits. In some locations, the exposure to UVB radiation is more than 16 times the minimum erythematous dose for phototype II skin. LIMITATIONS: This study assessed the radiation received during only four days. However, is a much higher number than most of the published papers. CONCLUSION: Although the health risks of excessive exposure to UV radiation are known, Barcelona's beach lifeguards are insufficiently protected.

[Translated article] Reflectance Confocal Microscopy Terminology in Spanish: A Delphi Consensus Study.

The terminology used to describe reflectance confocal microscopy (RCM) findings in both melanocytic and nonmelanocytic lesions has been standardized in English. We convened a panel of Spanish-speaking RCM experts and used the Delphi method to seek consensus on which Spanish terms best describe RCM findings in this setting. The experts agreed on 52 terms: 28 for melanocytic lesions and 24 for nonmelanocytic lesions. The resulting terminology will facilitate homogenization, leading to a better understanding of structures, more standardized descriptions in clinical registries, and easier interpretation of clinical reports exchanged between dermatologists.

Concordance of in vivo reflectance confocal microscopy and horizontal-sectioning histology in skin tumours.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) enables the study of architectural and cytological aspects in horizontal sections, which closely correlate with histologic features. However, traditional histopathological vertical sections cannot totally reproduce the image of the in vivo RCM horizontal section. OBJECTIVE: To evaluate the concordance between in vivo RCM and histopathologic transverse sections for melanocytic lesions, basal cell carcinoma and seborrheic keratoses. METHODS: Prospectively collected benign melanocytic and non-melanocytic tumours diagnosed by dermoscopy were evaluated for common RCM features and compared to histopathology in horizontal sections with haematoxylin and eosin staining. RESULTS: A total of 44 skin tumours including 19 melanocytic lesions (nine compound, five junctional and five intradermal nevi), 12 basal cell carcinomas and 13 seborrheic keratoses were collected in the Department of Dermatology of Hospital Clinic of Barcelona. The RCM features that had statistically significant agreement with the histopathological horizontal sections were the preserved and visible honeycomb pattern, well defined DEJ, small bright particles, dermal nests, tumour islands and dark silhouettes, clefting, collagen bundles, thickened collagen bundles and cytologic atypia. CONCLUSIONS: Histopathology evaluation of horizontal sections of skin tumours can be correlated with main RCM findings. The results of this study have improved the understanding and interpretation of RCM features in relation to skin tumours, thus reinforcing the utility of RCM as a diagnostic tool.

Understanding the anatomy of dermoscopy of melanocytic skin tumours: Correlation in vivo with line-field optical coherence tomography.

BACKGROUND: Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. OBJECTIVES: The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. METHODS: Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. RESULTS: 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. CONCLUSIONS: LC-OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.

Exposure to UV Radiation in Lifeguards on Barcelona's Beaches: An Underestimated Occupational Risk.

BACKGROUND: The development of skin cancer is closely related to high exposure to UV radiation. Lifeguards are at an increased risk of excessive sun exposure. OBJECTIVES: The main objective of this study was to measure the exposure of Barcelona's beach lifeguards to UV radiation. METHODS: Measurements in the work chair were taken every 30min on a typical working day from 10:45 am to 19:15 pm. These measurements were carried out on four different days. These data were used to calculate the erythematous doses received during working hours, as well as those potentially received throughout the summer season. Vitamin D production was also estimated for the four days that the radiation received was measured, and the amount generated was calculated for the entire summer season. RESULTS: Exposure to UV radiation among Barcelona lifeguards far exceeds safety limits. In some locations, the exposure to UVB radiation is more than 16 times the minimum erythematous dose for phototype II skin. LIMITATIONS: This study assessed the radiation received during only four days. However, is a much higher number than most of the published papers. CONCLUSION: Although the health risks of excessive exposure to UV radiation are known, Barcelona's beach lifeguards are insufficiently protected.

Reflectance Confocal Microscopy Terminology in Spanish: A Delphi Consensus Study. / Consenso de terminología en microscopia confocal de reflectancia en español mediante método Delphi.

The terminology used to describe reflectance confocal microscopy (RCM) findings in both melanocytic and nonmelanocytic lesions has been standardized in English. We convened a panel of Spanish-speaking RCM experts and used the Delphi method to seek consensus on which Spanish terms best describe RCM findings in this setting. The experts agreed on 52 terms: 28 for melanocytic lesions and 24 for nonmelanocytic lesions. The resulting terminology will facilitate homogenization, leading to a better understanding of structures, more standardized descriptions in clinical registries, and easier interpretation of clinical reports exchanged between dermatologists.

High- and intermediate-risk susceptibility variants in melanoma families from the Mediterranean area: A multicentre cohort from the MelaNostrum Consortium.

BACKGROUND: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark-skinned individuals, are underrepresented. OBJECTIVES: We report a comprehensive pooled analysis of established high- and intermediate-penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium. METHODS: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country. RESULTS: We included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1; 95% CI 3.3-19.7), >3 affected members (OR 2.6; 95% CI 1.3-5.2) and occurrence of pancreatic cancer (OR 4.8; 95% CI 2.4-9.4) in the family (AUC 0.76, 95% CI 0.71-0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4; 95% CI 1.0-2.0 and OR 4.3; 95% CI 1.2-14.6, respectively). CONCLUSIONS: Variants in known high-penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk assessment.

Development and validation of a minimally invasive and image-guided tape stripping method to sample atopic skin in children.

BACKGROUND: Molecular skin profiling techniques, typically performed on skin samples taken by punch biopsy, have enhanced the understanding of the pathophysiology of atopic dermatitis (AD), thereby enabling the development of novel targeted therapeutics. However, punch biopsies are not always feasible or desirable, and novel minimally invasive methods such as skin tape stripping have been developed. AIM: To develop, optimize and validate a novel tape stripping method guided by noninvasive in vivo skin imaging to sample atopic skin in children. METHODS: Skin tape stripping-based procedures were compared and optimized using data from 30 healthy controls (HCs: 5 adults, 25 children) and 39 atopic children. Evaluations were guided by high-resolution photography, reflectance confocal microscopy, optical coherence tomography and transepidermal water loss measurements. We assessed and compared adverse events (AEs), the time needed to perform the sampling and the cDNA levels obtained from the tapes. RESULTS: Tape stripping methods based on previously described protocols resulted in erosions in all participants and required a median time of 65 min to perform (range 60-70 min), but provided good cDNA yield. Shorter durations appeared less invasive but provided lower cDNA yield. The final optimized tape stripping protocol, using 11 tapes of 22 mm in diameter, each applied twice for 5 s with 90° rotation, did not produce significant AEs, was completed within a median time of 7 min (range 5-15 min) and provided good cDNA yield both in HCs and atopic children. CONCLUSION: Our minimally invasive method is safe and reliable, and provides reproducible acquisition of cDNA in atopic children. In addition, it enables rapid sample collection, a crucial factor in clinical practice.

CO2 in indoor environments: From environmental and health risk to potential renewable carbon source.

In the developed world, individuals spend most of their time indoors. Poor Indoor Air Quality (IAQ) has a wide range of effects on human health. The burden of disease associated with indoor air accounts for millions of premature deaths related to exposure to Indoor Air Pollutants (IAPs). Among them, CO2 is the most common one, and is commonly used as a metric of IAQ. Indoor CO2 concentrations can be significantly higher than outdoors due to human metabolism and activities. Even in presence of ventilation, controlling the CO2 concentration below the Indoor Air Guideline Values (IAGVs) is a challenge, and many indoor environments including schools, offices and transportation exceed the recommended value of 1000 ppmv. This is often accompanied by high concentration of other pollutants, including bio-effluents such as viruses, and the importance of mitigating the transmission of airborne diseases has been highlighted by the COVID-19 pandemic. On the other hand, the relatively high CO2 concentration of indoor environments presents a thermodynamic advantage for direct air capture (DAC) in comparison to atmospheric CO2 concentration. This review aims to describe the issues associated with poor IAQ, and to demonstrate the potential of indoor CO2 DAC to purify indoor air while generating a renewable carbon stream that can replace conventional carbon sources as a building block for chemical production, contributing to the circular economy.

Boosting ethanol production rates from carbon dioxide in MES cells under optimal solventogenic conditions.

Microbial Electrosynthesis (MES) has been widely applied for acetic acid (HA) production from CO2 and electricity. Ethanol (EtOH) has a higher market value than HA, and wide application in industry and as a biofuel. However, it has only been obtained sporadically and at low concentrations, probably due to sub-optimal operating conditions. This study aimed at enhancing EtOH productivity in MES cells by jointly optimising key operation parameters, including pH, H2 and CO2 partial pressure (pH2 and pCO2), and HA concentration, to promote solventogenesis. Two H-type cells were operated in fed-batch mode at -0.8 V vs. SHE with CO2 as the sole carbon source. A mixed culture, enriched with Clostridium ljungdahlii was used as the biocatalyst. The combination of low pH (<4.5) and pCO2 (<0.3 atm), along with high HA concentration (about 6 g L-1) and pH2 (>3 atm), were mandatory conditions for maintaining an efficient solventogenic culture, dominated by Clostridium sp., capable of high-rate EtOH production. The maximum EtOH production rate was 10.95 g m-2 d-1, and a concentration of 5.28 g L-1 was achieved. Up to 30 % of the electrons and 15.2 % of the carbon provided were directed towards EtOH production, and 28.1 kWh were required for the synthesis of 1 kg of EtOH from CO2. These results highlight that strict conditions are required for a continuous, reliable, EtOH production in MES cells. Future investigation should focus on improving cell configuration to achieve EtOH production at higher current densities while minimizing the electric energy input.

Phosphorus recovery from high solid content liquid fraction of digestate using seawater bittern as the magnesium source.

Phosphorus recovery from digestate is considered a challenge because the possible discharge can lead to eutrophication. This study focuses on phosphorus recovery as struvite from the liquid fraction of swine manure digestate at a high total solids concentration, by using a lab-scale crystallizer operated in continuous mode (7 L·d-1). A by-product of salt production (seawater bittern, SWB) was assessed as Mg source for the formation of struvite instead of a chemical dosage (MgCl2) within a circular economy approach. Different Mg/P (1.8:1; 2:1; 3:1) ratios and different TS contents (TS 3.5 and 4.5 %) were studied. The maximum P recovery of 85 % and N recovery of 52 % was obtained at 4.5 % of TS and Mg/P ratio of 2:1, corresponding to an overall P and N recovery on the raw digestate of 70 % and 46 %, respectively. The presence of struvite was confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM-EDS). Dried samples were then used as fertilizer in agronomic pot tests using Brassica rapa chinensis. Struvite obtained, showed comparable fertilizing properties in comparison with conventional fertilizers in terms of P (Mineral 5.6 ± 0.4; Poultry 5.7 ± 0.2; Struvite 5.9 ± 0.1 g kg-1), N and total biomass content such as chlorophylls ratio. The growth tests confirmed the possible use of struvite recovered as competitive alternative to conventional chemical phosphate fertilizers. The results showed that it can be possible to promote sustainable P recovery from high solids digestates by the combination of crystallizer reactor and Mg-salt byproducts.

Sinonasal mucosal melanomas: defining profiles for better survival outcomes.

BACKGROUND: Sinonasal mucosal melanoma is an aggressive malignancy with a 5-year survival rate ranging from 20% to 39%. Despite the evolving surgical and radiotherapy techniques, and introduction of immune-checkpoint inhibitor therapy, overall survival rates remain poor. METHODOLOGY: A retrospective cohort study was conducted at the Hospital Clinic de Barcelona and the Hospital de la Santa Creu i Sant Pau between 1984 and 2020; primary outcome measures were 3 and 5-year melanoma-specific survival (MSS). Kaplan-Meier survival analysis and Cox proportional hazards model were performed to identify predictors of survival. RESULTS: Fifty patients were included, the mean age was 70.4, MSS at 3 and 5 years was 51.2%, and 29.5%, respectively. The median follow-up was 39.6 months during which 46% presented locoregional recurrence and 36%, metastasis. The univariate and multivariate analyses found as survival predictors the N category, the treatment received, the surgical margins and the mitotic index. CONCLUSIONS: We found an overall 5-year MSS of 29.5%. Those patients with intention-to-cure (stages III and IVa) treated by surgery that were N0 at diagnosis, with < 10 mitoses per HPF showed a 5-year MSS rate of 74.1%. More studies will be needed to adequately define the patients' profiles that will benefit from a better survival outcome.

Synchronous primary cutaneous melanomas: a descriptive study of their clinical features, histology, genetic background of the patients and clinical outcomes.

BACKGROUND: Around 0.5% of cutaneous melanoma (CM) patients will present with synchronous melanomas when first seen. Moreover, 26-40% of patients with multiple primary melanomas present with synchronous lesions. OBJECTIVES: To assess the prevalence, clinical and histopathological characteristics, germline mutations and outcome in patients with synchronous melanoma. METHODS: Clinical and histopathological data from 4703 melanoma patients were included. Clinical, histological and genetic mutational status information was analysed. Kaplan-Meier curves were used to investigate survival outcomes. RESULTS: A total of 144 patients (3.06%) presented simultaneously with two or more primary melanomas. During follow-up, 25.7% of patients with synchronous melanoma developed a new primary melanoma compared to 8.6% of patients diagnosed with single melanoma (P < 0.001). Germinal CDKN2A mutations were identified in 10.7% of patients with synchronous melanomas and genetic variants in MC1R in 72%. No significant differences in all survival outcomes between patients with synchronous melanomas and single melanomas were found. CONCLUSION: Synchronous melanomas are more frequent than previously reported and are more frequent in older patients compared to single melanomas. Moreover, these patients have a higher risk of developing a new primary melanoma during follow-up and have higher rates of germline susceptibility variants. Nevertheless, these findings were not associated with worse outcomes.