Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real-life clinical practice.

Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.

Parents' 'fault' must not weigh on their children. Surrogacy as a universal crime in Italy: Is it compatible with bioethical principles?

Abstract: Assisted reproduction techniques (ARTs) have given rise to novel, non-traditional family models. Still, among the various applications and approaches of 'medically assisted procreation' (MAP), the most divisive one undoubtedly is 'gestational surrogacy' (GS), also in light of the rising number of couples who have chosen it over the past twenty years. Another major implication of ARTs is the creation of intentional (or intended) parenthood in addition to genetic one: the genetic parent's partner is thus defined as the intentional (or second) parent, who by free choice, shares the family project with the genetic parent, even without any biological tie with the child. Hence, the intended parent takes on the same rights and responsibilities towards the child as the biological one. Several countries, including Italy, have enacted norms to discourage cross-border surrogacy, deeming it harmful to the dignity of women and children. Recently, however, the Italian government has decided intensify the fight against this practice: the Chamber of Deputies (Italy's lower chamber of parliament) has passed a law which punishes couples that resort to surrogacy even if the agreement and the birth take place abroad. Therefore, surrogacy would become a so-called universal crime. In light of the fact that criminalization is a serious and highly consequential step, which may have life-changing consequences for the intended parents, the aim of this paper is to assess whether this may be an effective instrument for regulating the interests at stake and, therefore, whether it would be desirable for other countries to follow such a model. Ultimately, it is worth remarking that for those who seek to achieve parenthood, such a desire is among the most profound aspects of a person's existential realization. When due to a delicate balance of ethics standards and potentially conflicting rights, lawmakers inter-vene, an authoritarian approach is unlikely to be beneficial. Offering real alternatives to surrogacy in an organic and pragmatic fashion (i.e. expediting adoption procedures, favoring motherhood at a younger age, when infertility issues are less likely to have set in) may be the best way to disincentivize fertility traveling and make sure the rights, hopes and aspirations of all the parties involved are upheld properly.

Development and validation of AI-assisted transcriptomic signatures to personalize adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: After surgical resection of pancreatic ductal adenocarcinoma (PDAC), patients are predominantly treated with adjuvant chemotherapy, commonly consisting of gemcitabine (GEM)-based regimens or the modified FOLFIRINOX (mFFX) regimen. While mFFX regimen has been shown to be more effective than GEM-based regimens, it is also associated with higher toxicity. Current treatment decisions are based on patient performance status rather than on the molecular characteristics of the tumor. To address this gap, the goal of this study was to develop drug-specific transcriptomic signatures for personalized chemotherapy treatment. PATIENTS AND METHODS: We used PDAC datasets from preclinical models, encompassing chemotherapy response profiles for the mFFX regimen components. From them we identified specific gene transcripts associated with chemotherapy response. Three transcriptomic artificial intelligence signatures were obtained by combining independent component analysis and the least absolute shrinkage and selection operator-random forest approach. We integrated a previously developed GEM signature with three newly developed ones. The machine learning strategy employed to enhance these signatures incorporates transcriptomic features from the tumor microenvironment, leading to the development of the 'Pancreas-View' tool ultimately clinically validated in a cohort of 343 patients from the PRODIGE-24/CCTG PA6 trial. RESULTS: Patients who were predicted to be sensitive to the administered drugs (n = 164; 47.8%) had longer disease-free survival (DFS) than the other patients. The median DFS in the mFFX-sensitive group treated with mFFX was 50.0 months [stratified hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.21-0.44, P < 0.001] and 33.7 months (stratified HR 0.40, 95% CI 0.17-0.59, P < 0.001) in the GEM-sensitive group when treated with GEM. Comparatively patients with signature predictions unmatched with the treatments (n = 86; 25.1%) or those resistant to all drugs (n = 93; 27.1%) had shorter DFS (10.6 and 10.8 months, respectively). CONCLUSIONS: This study presents a transcriptome-based tool that was developed using preclinical models and machine learning to accurately predict sensitivity to mFFX and GEM.

Use of CYP2D6 substrates and inhibitors during pain management with analgesic opioids: Drug-drug interactions that lead to lack of analgesic effectiveness.

BACKGROUND: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes. MATERIALS AND METHODS: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded. RESULTS: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present. CONCLUSION: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.

Postoperative pain in dogs undergoing either laparoscopic or open ovariectomy.

A prospective, quasi-experimental, clinical trial was performed to assess acute postoperative pain in healthy female dogs following elective ovariectomy by either laparoscopy (n=13) or laparotomy (n=14). Pain was assessed by both a veterinarian at the hospital, and by the owner once the patient was discharged. The Spanish version of the short form of the Glasgow Composite Measuring Pain Scale (CMPS-SF) was used. Pain scores were assessed by the veterinarian preoperatively and at 1, 2, 4, and 6 h after extubation, whilst owner-assessed scores were performed preoperatively and at postoperative days 0, 1, 2, 3, 5 and 7. Data were compared with Mann-Whitney-U test. Veterinarian-assessed CMPS-SF scores were different between both groups at all postoperative times but not at baseline, being below 6/24 in all dogs in the laparoscopy group, but equal to or greater than 6/24 in the laparotomy group at 1 h (n=12), and 4 h (n=4) (P<0.001 and P=0.029, respectively). There were also differences in pain scores between both groups at 2 h (P=0.012) and 6 h (P=0.007), being below 6/24 in all of them. However, there were no differences in owner assessments between groups. In conclusion, ovariectomy performed by laparoscopy induced lower pain scores that were below the pain threshold set by the CMPS-SF during the first 6 h postoperatively. After discharge, and up to one week later, ongoing owner-assessed scores suggest no pain was induced with neither of the techniques. Owners were proactive allowing real-time pain assessment to be reported. The development and validation of instruments for acute pain assessment by owners is warranted, as these tools are currently lacking.

In vitro exposure of porcine spermatozoa to methylparaben, and propylparaben, alone or in combination adversely affects sperm quality.

Parabens (PBs) are widely used in the cosmetic, pharmaceutical, and food industries as preservatives of products. Because of its great use, humans and other organisms are highly exposed daily. However, little is known about the effect of PBs on male infertility. Therefore, the aim of the present study was to evaluate the effect of methylparaben (MePB) and propylparaben (PrPB), alone or in combination, on the physiological characteristics of pig in vitro exposed sperm to different concentrations (0, 200, 500, and 700 µM) for viability, motility, and acrosome integrity evaluation and (0, 200, 500, 700, 1000, and 2000 µM) for DNA fragmentation index evaluation, after 4 h of exposure. The results showed that sperm viability decreased after exposure to MePB from the concentration of 500 µM. In the PrPB and mixture groups, viability decreased at all concentrations except for the control. The decrease in viability of sperm exposed to PrPB was greater than that of the mixture and MePB groups. Sperm motility decreased in all the experimental groups exposed to PBs, at all concentrations, except for the control group. Acrosome integrity was not decreased in the MePB group; however, in the PrPB group, it decreased at a concentration of 200 µM and in the mixture at 500 µM. All groups exhibited DNA damage at different concentrations, except for the control group. Additionally, the effect of PBs on sperm quality was concentration-dependent. The results demonstrated that MePB and PrPB alone or in combination can have adverse effects on sperm quality parameters. MePB had lower toxicity than did both PrPB and the mixture. The mixture did not have an additive effect on any of the parameters evaluated. This could partially explain the link between PB exposure and infertility.

Evaluation of macular integrity, after retinal detachment surgery, using MAIA microperimetry.

BACKGROUND AND OBJECTIVE: To describe visual function, macular integrity, and fixation stability using MAIA microperimetry (macular integrity assessment) after retinal detachment surgery. Evaluate if there are statistically significant differences between surgical approaches. MATERIALS AND METHODS: A prospective, comparative, interventional study was conducted, recruiting a total of 21 patients with rhegmatogenous retinal detachment and macula-off. Eleven patients underwent surgery using pars plana vitrectomy (PPV), and 10 patients underwent scleral buckle surgery. Clinical examinations and optical coherence tomography (OCT) were performed post-surgery. MAIA microperimetry was conducted at 6 months. RESULTS: Best-corrected visual acuity (BCVA) and the number of letters read improved over time in the operated eye but did not reach the level of the control eye (p = 0.001). No significant differences were found between the two surgical approaches in BCVA (p = 0.230) or the number of letters read (p = 0.608). Macular integrity in the operated eye did not match that of the control eye in both procedures (p = 0.05). No differences were detected between the two surgeries, either in macular integrity (p = 0.512) or fixation stability (p = 0.835). CONCLUSIONS: Following retinal detachment surgery, a decrease in BCVA and the number of letters read occurs, which does not reach the level of the control eye. No significant differences were observed between the two surgical approaches. Macular integrity in the operated eye does not match that of the control eye.

Pharmacological induction of diabetes mellitus in pregnant female mice: a comparison of two doses and routes of administration.

OBJECTIVE: This study aimed to compare two routes of administration and different dosages of streptozotocin (STZ) for the pharmacological induction of gestational diabetes mellitus (GDM) in pregnant CD1 females. MATERIALS AND METHODS: 35 female CD1 mice were divided into 5 groups (n = 7). Diabetes mellitus (DM) was induced with STZ by two routes and two doses: 1) Control Group without administration of STZ (CL), 2) Intraperitoneal Group with 200 mg of STZ/Kg of weight (IP200), 3) Intraperitoneal Group with 230 mg of STZ/Kg of weight (IP230), 4) Subcutaneous Group with 200 mg of STZ/Kg of weight (SC200) and 5) Subcutaneous Group with 230 mg of STZ/Kg of weight (SC230). Body weight, food and water intake, glycemia, Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR), survival, and birth rate were identified. RESULTS: The SC230 group turned out to be the most effective dose and route for the induction of GDM in pregnant females. This scheme managed to reproduce sustained hyperglycemia with high HOMA-IR, the presence of polyphagia, polydipsia, and weight loss. In addition, the birth rate and survival were high compared to the other doses and routes of administration. CONCLUSIONS: The administration of a single dose of 230 mg/kg of weight by subcutaneous route supposes advantages compared to previously used models since it decreases the physiological stress due to manipulation and the costs since it does not require repeated doses or adjuvants such as high lipid diets to potentiate the diabetogenic effect of STZ. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-12.jpg.

Do NO, N2O, N2 and CO2 fluxes differ in soils sourced from cropland and varying riparian buffer vegetation? An incubation study.

Riparian buffers are expedient interventions for water quality functions in agricultural landscapes. However, the choice of vegetation and management affects soil microbial communities, which in turn affect nutrient cycling and the production and emission of gases such as nitric oxide (NO), nitrous oxide (N2O), nitrogen gas (N2) and carbon dioxide (CO2). To investigate the potential fluxes of the above-mentioned gases, soil samples were collected from a cropland and downslope grass, willow and woodland riparian buffers from a replicated plot scale experimental facility. The soils were re-packed into cores and to investigate their potential to produce the aforementioned gases via potential denitrification, a potassium nitrate (KNO3 -) and glucose (labile carbon)-containing amendment, was added prior to incubation in a specialized laboratory DENItrification System (DENIS). The resulting NO, N2O, N2 and CO2 emissions were measured simultaneously, with the most NO (2.9 ± 0.31 mg NO m-2) and N2O (1413.4 ± 448.3 mg N2O m-2) generated by the grass riparian buffer and the most N2 (698.1 ± 270.3 mg N2 m-2) and CO2 (27,558.3 ± 128.9 mg CO2 m-2) produced by the willow riparian buffer. Thus, the results show that grass riparian buffer soils have a greater NO3 - removal capacity, evidenced by their large potential denitrification rates, while the willow riparian buffers may be an effective riparian buffer as its soils potentially promote complete denitrification to N2, especially in areas with similar conditions to the current study.

Chemical analysis of marine microdebris pollution in macroalgae from the coastal areas of Argentina.

Marine microdebris (MDs, <5 mm) and mesodebris (MesDs, 5-25 mm), consist of various components, including microplastics (MPs), antifouling or anticorrosive paint particles (APPs), and metallic particles (Mmps), among others. The accumulation of these anthropogenic particles in macroalgae could have significant implications within coastal ecosystems because of the role of macroalgae as primary producers and their subsequent transfer within the trophic chain. Therefore, the objectives of this study were to determine the abundance of MDs and MesDs pollution in different species of macroalgae (P. morrowii, C. rubrum, Ulva spp., and B. minima) and in surface waters from the Southwest Atlantic coast of Argentina to evaluate the ecological damage. MDs and MesDs were chemically characterized using µ-FTIR and SEM/EDX to identify, and assess their environmental impact based on their composition and degree of pollution by MPs, calculating the Polymer Hazard Index (PHI). The prevalence of MDs was higher in foliose species, followed by filamentous and tubular ones, ranging from 0 to 1.22 items/g w.w. for MPs and 0 to 0.85 items/g w.w. for APPs. It was found that macroalgae accumulate a higher proportion of high-density polymers like PAN and PES, as well as APPs based on alkyd, PMMA, and PE resins, whereas a predominance of CE was observed in surrounding waters. Potentially toxic elements, such as Cr, Cu, and Ti, were detected in APPs and MPs, along with the presence of epiplastic communities on the surface of APPs. According to PHI, the presence of high hazard score polymers, such as PAN and PA, increased the overall risk of MP pollution in macroalgae compared to surrounding waters. This study provided a baseline for MDs and MesDs abundance in macroalgae as well as understanding the environmental impact of this debris and their bioaccumulation in the primary link of the coastal trophic chain.

Dose-escalated SBRT for borderline and locally advanced pancreatic cancer. Feasibility, safety and preliminary clinical results of a multicenter study.

Background: Pancreatic Stereotactic Body Radiotherapy (SBRT) allows for the administration of a higher biologically effective doses (BED), that would be essential to achieve durable tumor control. Escalating treatment doses need a very accurate tumor positioning and motion control during radiotherapy.The aim of this study to assess the feasibility and safety of a Simultaneous Integrated Boost (SIB) dose-escalated protocol at 45 Gy, 50 Gy and 55 Gy in 5 consecutive daily fractions, in Border Line Resectable Pancreatic Cancer (BRCP) /Locally Advanced Pancreatic Cancer (LAPC) by means of a standard LINAC platform. Methods: Patients diagnosed of BRPC/LAPC, candidates for neoadjuvant chemotherapy and SBRT, in four university hospitals of the province of Las Palmas (Canary Islands, Spain) were included in this prospective study. Radiotherapy was administered using standard technology (LINACS) with advanced positioning (Lipiodol® and metallic stent used as fiducial markers) and tumor motion control (4D, DBH, Calypso®). There were 3 planned dose-escalated SIB groups, 45 Gy/5f (9 patients) 50 Gy/5f (9 + 9 patients) and 55 Gy/5f (9 patients). The defined primary end points of the study were the safety and feasibility of the proposed treatment protocol. Secondary endpoints included radiological tumor response after SBRT, local control and survival. Results: From June 2017 to December 2022, sixty-two patients were initially assessed for eligibility in the study in the four participating centers, and 49 were candidates for chemotherapy (CHT). Forty-one were referred to radiotherapy after CHT and 33 finally were treated by escalated-dose SIB, 45 Gy (9 patients) 50 Gy (16 patients), 55 Gy(8 patients). All patients completed the scheduled treatment and no acute or late severe (≥grade3) gastrointestinal toxicity was observed.Local response was analyzed by CT/MRI two months after the end of SBRT. Ten patients (31,25 %) achieved objective response (2/9:45 Gy, 5/15:50 Gy, 3/8:55 Gy). Follow-up was closed as July 2023. Freedom from local progression at 1-2y were 89,3% (95 %CI:83,4-95,2%) and 66 % (95 %CI:54,6-77,4%) respectively. The 1-2y survival rates were 95,7% (95 %CI:91,4-100 % and 48,6% (95 %CI:37,7-59,5%) respectively. Conclusion: These promising results should be confirmed by further studies with larger sample size and extended follow-up period.

Burnout Syndrome, Anxiety, and Depression in Dermatology Residents: A Cross-Sectional Study. / Síndrome de burnout, ansiedad y depresión en residentes de dermatología: un estudio transversal.

BACKGROUND AND OBJECTIVE: Burnout syndrome is a mental health disorder due to chronic occupational stress. Both burnout and associated comorbidities are prevalent among health care professionals, being medical residents a vulnerable group. Despite this, the scientific medical literature currently available on this issue in dermatology residents is scarce. The aim of this study was to analyze the prevalence of the burnout syndrome, anxiety, and depression in dermatology residents, and the associated risk factors. MATERIAL AND METHOD: This was a cross-sectional trial designed to include dermatology residents from Spain (from December 2022 through June 2023). A self-administered form was sent via online messaging applications, including validated scales to study professional quality of life, burnout syndrome, anxiety, and depression. RESULTS: A total of 48 dermatology residents were included in the study, 50% of whom (24/48) were women, with a mean age of 27 years (1.25). A total of 58.33% (28/48) of the residents had some degree of anxiety, 22.9% (11/48) some degree of depression, and 23.4% a moderate risk of burnout (11/48). Workload was the main risk factor associated with the 3 disorders studied, while managerial support or intrinsic motivation seem to play a protective role. CONCLUSIONS: Burnout syndrome and its comorbidities are both prevalent in dermatology residents in Spain and closely related to each other.

Ocular neuromyotonia: an unusual case after radiotheraphy for nasopharyngeal carcinoma.

Ocular neuromyotonia (ONM) is an infrequent disorder characterised by recurrent episodes of binocular diplopia caused by paroxysmal contraction of one or several extraocular muscles innervated by the same cranial nerve. It can be triggered spontaneously or caused by prolonged contraction of specific eye muscle(s) and is usually related to a local intracranial radiotherapy antecedent. We report the case of a 46-year-old woman who developed intermittent episodes of binocular diplopia eight years after radiotherapy for a nasopharyngeal carcinoma. After a complete neuro-ophthalmic assessment we diagnosed the case as an abducens nerve neuromyotonia. Although it is infrequent, radiotherapy to the nasopharynx is a possible cause of ONM, due to the proximity to the base of the skull and extraocular motor nerve pathways, especially that of the VI cranial nerve, as is the case presented in this article, about a patient whose history is a nasopharyngeal carcinoma treated with local radiotherapy.

Photodissociation of the CH2Br radical: A theoretical study.

Bromine atom (Br) reactions lead to ozone depletion in the troposphere and stratosphere. Photodegradation of bromocarbons is one of the main sources of bromine atoms in the atmosphere. Here, we use high-level ab initio methods, including spin-orbit effects, to study the photodissociation of the CH2Br radical. All possible fragmentation pathways, namely CH2Br + hν → CH2 + Br, HCBr + H, and CBr + H2, have been analyzed. Potential-energy curves of the ground and several excited electronic states along the corresponding dissociating bond distance of each pathway have been calculated. Considering the actinic fluxes of solar irradiation in the troposphere and in the stratosphere in the relevant range of frequencies, it is found that the first five excited states of CH2Br can be accessed from the ground state. Analysis of the potential curves shows that the pathways producing CH2 + Br and HCBr + H can proceed through a fast direct dissociation mechanism, while the pathway leading to CBr + H2 involves much slower dissociation mechanisms like internal conversion between electronic states, predissociation, or tunneling through exit barriers. The main implications are that the two faster channels are predicted to be dominant, and the slower pathway is expected to be less relevant. The tropospheric and stratospheric solar actinic fluxes also allow for further dissociation of the HCBr and CBr fragments, generating additional Br atoms, provided that they survive possible collisions with other atmospheric reagents. Finally, we discuss the possible effect of each of the three CH2Br dissociation pathways on the depletion of atmospheric ozone.

Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors. / [Artículo traducido] Impacto de la pandemia COVID-19 en el carcinoma de células escamosas cutáneo: un estudio unicéntrico de los factores epidemiológicos, clínicos e histopatológicos.

BACKGROUND: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. OBJECTIVE: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. MATERIAL & METHODS: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. RESULTS: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. CONCLUSIONS: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.