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Background and Objective: Psoriasis often precedes the onset of psoriatic arthritis (PsA), so dermatologists often face the challenge of early identifying signs of PsA in patients with psoriasis. Our aim was to validate the Spanish version of the PURE-4 questionnaire as a screening tool for PsA, evaluate its performance in terms of sensitivity, specificity, feasibility, reliability, and build validity., Methods: This was a cross-sectional, observational, multicenter trial of adult patients with psoriasis. Initially, patients were assessed by a dermatologist and completed 2 self-administered versions (in print and online) of the PURE-4 questionnaire. Afterwards, the rheumatologist, blinded to the PURE-4 results, assessed the presence/absence of PsA, being the reference to determine the performance of the PURE-4 questionnaire., Results: A total of 268 patients were included (115 [42.9%] women; mean age, 47.1±12.6). The prevalence of PsA according to rheumatologist diagnosis was 12.7% (34 patients). The mean PURE-4 score for patients with psoriasis diagnosed with PsA was 2.3±1.1, and 1.3±1.3 for patients without PsA (P<.001). The cutoff value ≥2 demonstrated the best performance for detecting PsA, with a negative predictive value of 95.1% (95% confidence interval, 90.3-97.6)., Conclusions: The PURE-4 questionnaire demonstrated good performance in detecting PsA, with an optimal cutoff point ≥2. This simple tool could facilitate early referral of patients to the rheumatology unit., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objective: Cutaneous squamous cell carcinoma (cSCC) is the second leading cause of skin cancer mortality in Europe. Few studies have analyzed the different pathways of this tumor progression in its natural history. The main objective of this study was to analyze the different metastatic and progression pathways and their temporal occurrence in the evolution of cSCC., Material and Method: We conducted a multicenter, retrospective, and observational study of consecutive high-risk sSCCs included in the SQUAMATA project., Results: A total of 222 out of the 1346 patients included relapsed. The most frequent route of progression was the lymphatic one (62.6%). A total of 20.2% of the cases with lymphatic progression developed distant metastases. Only 1 case (3.1%) of distant metastasis followed local recurrence without previous lymphatic metastasis. The median time to disease-related mortality was longer in patients who developed systemic metastases than in those who died of locoregional progression., Conclusions: The mortality of patients with cSCC is mostly due to the regional progression of their lymphatic metastases. The appearance of distant metastases is practically always (96.9%) associated with previous lymphatic metastatic progression. Therefore, in the future, new studies will be needed to assess the regional management of cSCC in both surgical and adjuvant therapies., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. The incidence of metastasis for cSCC is estimated to be around 1.2-5%. Ribosomal protein S6 (p-S6) and the p21 protein (p21) are two proteins that play central roles in other cancers. These proteins may be equally important in cSCC, and together, these could constitute a good candidate for metastasis risk assessment of these patients. We investigate the relationship of p-S6 and p21 expression with the impact on the prognosis of head and neck cSCC (cSCCHN). p-S6 and p21 expression was analyzed by immunohistochemistry on paraffin-embedded tissue samples from 116 patients with cSCCHN and associations sought with clinical characteristics. Kaplan-Meier estimators and Cox proportional hazard regression models were also used. The expression of p-S6 was significantly inversely associated with tumor thickness, tumor size, desmoplastic growth, pathological stage, perineural invasion and tumor buds. p21 expression was significantly inversely correlated with >6 mm tumor thickness, desmoplastic growth, and perineural invasion. p-S6-negative expression significantly predicted an increased risk of nodal metastasis (HR = 2.63, 95% CI 1.51-4.54; p < 0.001). p21 expression was not found to be a significant risk factor for nodal metastasis. These findings demonstrate that p-S6-negative expression is an independent predictor of nodal metastasis. The immunohistochemical expression of p-S6 might aid in better risk stratification and management of patients with cSCCHN.

PTEN-induced kinase-1 (PINK1) is the initiator of the canonical mitophagy pathway. Our aim was to study the immunoexpression of PINK1 in surgical specimens from ninety patients with metastatic colorectal adenocarcinoma (CRC) to the liver (CRLM). Tissue arrays were produced, and immunohistochemical studies were analyzed by the H-Score method. The mean immunoexpression of PINK1 in normal tissues was between 40 to 100 points. In tumoral tissues, positive PINK1 immunoexpression was observed in all samples, and no differences were noted between CRCs. In CRLMs, a significant under-expression was noted for PINK1 from the rectum (71.3 ± 30.8; p < 0.042) compared to other sites. Altered PINK1 immunoexpression in CRCs, either higher than 100 points or lower than 40 points, was associated with worse overall survival (OS) ( p < 0.012) due to a shorter post-metastatic survival (PMS) ( p < 0.023), and it was found to be a significant independent predictor of prognosis in a multivariate model for OS and PMS (HR = 1.972, 95% CI 0.971-4.005; p = 0.022. HR = 2.023, 95% CI 1.003-4.091; p = 0.037, respectively). In conclusion, altered PINK1 immunoexpression determined in CRCs with resected CRLM predicts a worse prognosis, possibly due to the abnormal function of mitophagy.

The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas., (© 2023. The Author(s).)

Biological drugs have prompted a revolution in the treatment of patients with psoriasis because of their favourable efficacy/risk profile. The aims of our study are to determine whether there is any difference in the pattern of use of biological treatments for older (65+ years) and younger patients diagnosed with plaque psoriasis by the Dermatology Service of the Hospital Universitario de Asturias (HUCA), to understand the survival of these drugs, and to identify the factors that predict the discontinuation of treatments. We report a retrospective observational hospital-based study of 300 patients registered at HUCA's Dermatology Service who were receiving one of the following biological treatments for psoriasis on 30 November 2020: adalimumab, ustekinumab, secukinumab, or ixekizumab. The age groups were compared using Student's t-test for quantitative variables and the chi-squared test for qualitative variables. We used the Kaplan-Meier estimator to estimate the survival function and the log-rank test to measure differences. No statistically significant differences in the frequency of use were noted between the younger and older groups, for any of the drugs studied. Survival on a drug regime, globally and individually, was similar in the two age groups. Factors predicting lower overall survival were being female, obesity, and having undergone previous biological treatment. The first three factors were influential in the under-65-year-old group, while arthritis was a significant factor for the older group.

The aim of this study was to compare tumour burden in patients who underwent surgery for melanoma and cutaneous squamous cell carcinoma during nationwide lockdown in Spain due to COVID-19 (for the period 14 March to 13 June 2020) and during the same dates in 2019 before the COVID-19 pandemic. In addition, associations between median tumour burden (Breslow thickness for melanoma and maximum clinical diameter for cutaneous squamous cell carcinoma) and demographic, clinical, and medical factors were analysed, building a multivariate linear regression model. During the 3 months of lockdown, there was a significant decrease in skin tumours operated on (41% decrease for melanoma (n = 352 vs n = 207) and 44% decrease for cutaneous squamous cell carcinoma (n = 770 vs n = 429)) compared with the previous year. The proportion of large skin tumours operated on increased. Fear of SARS-CoV-2 infection, with respect to family member/close contact, and detection of the lesion by the patient or doctor, were related to thicker melanomas; and fear of being diagnosed with cancer, and detection of the lesion by the patient or relatives, were related to larger size cutaneous squamous cell carcinoma. In conclusion, lockdown due to COVID-19 has resulted in a reduction in treatment of skin cancer.

Barrett's esophagus (BE) is the most important risk factor for the development of esophageal adenocarcinoma. It develops through a progressive sequence of histologic and molecular events that begin with metaplasia and then progresses through various stages of dysplasia. Matrix metalloproteinases are involved in the degradation of the extracellular matrix and play an important role in tumor progression. The immunohistochemical expression of MMP-1, TIMP-2 and p53 in 111 samples from 45 patients diagnosed with BE with and without dysplasia and adenocarcinoma of the esophagus was retrospectively studied, and statistical analysis was conducted to measure the association between their expression and the degree of dysplasia present. MMP-1 was expressed in 33.3% of the samples studied, mainly in the adenocarcinoma subgroup with up to 40% positive cases (p = 0.494). In contrast, TIMP-2 was expressed in 25.2% of the samples, and no positive cases were identified in the adenocarcinoma subgroup (p = 0.037). Aberrant p53 expression was observed in 81.4% of the samples diagnosed with some degree of dysplasia (p < 0.001). MMP-1 showed no statistically significant differences between diagnostic entities. A statistically significant loss of TIMP-2 expression was observed in distal esophageal adenocarcinoma samples, which contrasts with the aberrant expression of p53 in dysplastic cases.

Background and objectives: The efficacy and safety of ustekinumab have been proved in clinical trials. In daily clinical practice, knowing the factors that determine survival differences of biological drugs allows psoriasis treatment to be optimized as a function of patient characteristics. The main objectives of this work are to understand ustekinumab drug survival in patients diagnosed with plaque psoriasis in the Hospital Universitario Central de Asturias (HUCA Dermatology Department, and to identify the predictors of drug discontinuation. Materials and Methods : A retrospective hospital-based study, including data from 148 patients who were receiving ustekinumab (Stelara ® ) between 1 February 2009 and 30 November 2019, were collected. Survival curves were approximated through the Kaplan-Meier estimator and compared using the log-rank test. Proportional hazard Cox regression models were used for multivariate analyses while both unadjusted and adjusted hazard ratios (HR) were used for summarizing the studied differences. Results: The average duration of the treatment before discontinuation was 47.57 months (SD 32.63 months; median 41 months). The retention rates were 82% (2 years), 66% (5 years), and 58% (8 years). Median survival was 80 months (95% confidence interval. CI 36.9 to 123.01 months). The survival study revealed statistically significant differences between patients with arthritis (log-rank test, p < 0.001) and those who had previously received biological treatment (log-rank test, p = 0.026). The five-year prevalence in patients still under treatment was 80% (those without arthritis) and 54% (arthritis patients). In the multivariate analysis, only the patients with arthritis had a lower rate of drug survival. No statistically significant differences were observed for any of the other comorbidities studied. The first and second most frequent causes of discontinuation were secondary failure and arthritis inefficacy, respectively. Conclusion: Ustekinumab is a biological drug conferring high survival in plaque psoriasis patients. Ustekinumab survival is lower in patients with arthritis.

Background and Objectives: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma., Material and Methods: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points., Results: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter >4cm or thickness >6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (>6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months., Conclusions: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays., (© 2020 Published by Elsevier España, S.L.U. on behalf of AEDV.)