Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts.

BACKGROUND: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas. OBJECTIVE: To generate a consensual and operational classification of cSCCs. METHOD: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners. RESULTS: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases. CONCLUSION: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

Longitudinal Study of Different Progression Patterns in High-Risk Cutaneous Squamous Cell Carcinoma. / Estudio longitudinal de los diferentes patrones de progresión en el carcinoma cutáneo de células escamosas de alto riesgo.

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.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study. / [Artículo traducido] Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study.

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

Melanoma in Solid Organ Transplant Recipients. / Melanoma en pacientes receptores de un trasplante de órgano sólido.

In this review, we analyze the 3 clinical scenarios related to the development of melanoma in solid organ transplant recipients: melanoma in patients with a history of the tumor prior to a transplant, de novo melanoma following a transplant, and melanoma of donor origin. The main factors to consider in organ-transplant candidates with a history of melanoma are tumor stage, presence or absence of residual disease, and time from diagnosis to transplantation. Solid organ transplant recipients have a greater risk of melanoma than immunocompetent individuals. Mortality is also higher in this population, especially in patients with advanced melanoma, as treatment is especially challenging. Clinical history and physical examination provide the most useful information for preventing donor-to-recipient transmission of melanoma. Donor-derived melanoma has a very poor prognosis.

[Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model]. / Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido al confinamiento por COVID-19: modelo basado en un crecimiento exponencial.

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.

Effects of pH and Application Technique of In-office Bleaching Gels on Hydrogen Peroxide Penetration into the Pulp Chamber.

OBJECTIVE: This in vitro study aimed to quantify the penetration of hydrogen peroxide (HP) into the pulp chamber in teeth submitted to in-office bleaching with varied pH and application techniques. The color change and pH of the in-office bleaching product during application was also evaluated. METHODS AND MATERIALS: Ninety-six human premolars were used and randomly divided into 10 groups (n=9) according to the following combination of factors: pH of in-office bleaching agents (two neutral/alkaline pH: Opalescence Boost 38% and Whiteness HP Blue 35% and three acidic pH: Whiteness HP Maxx 35%, Lase Peroxide Sensy 35%, and Total Blanc Office 35%) and application modes (for 3 × 15 minutes [3×15] and 1 × 45 minutes [1×45]). An additional group of non-bleached teeth (control; n=6) was added. First, all teeth were sectioned 3 mm from the cementoenamel junction and the pulp tissue was removed. An acetate buffer was placed in the pulp chamber of all teeth. After bleaching, this solution was transferred to a glass tube in which HP was allowed to react with other components, resulting in a pink solution. The optical density of this pink solution was measured using ultraviolet-visible spectroscopy and converted into amount of HP. Color change before and 1 week after bleaching was evaluated using a digital spectrophotometer. A pH meter with a 6-mm circular and flat surface was used in contact with the enamel surface to quantify the pH of the bleaching gels during application. Data were analyzed using two-way analysis of variance and Tukey tests (α=0.05). RESULTS: Overall, lower mean HP penetration values were observed for Opalescence Boost 38% and Whiteness HP Blue 35% compared with other bleaching gels (p<0.05). Opalescence Boost 38% and Whiteness HP Blue 35% were not influenced by the application technique (p>0.05). However, lower mean HP penetration values were observed for Whiteness HP Maxx 35%, Total Blanc Office 35%, and Lase Peroxide Sensy 35% when using the 3×15 application technique compared with the 1×45 technique (p<0.05). Significant whitening was detected and no significant difference of color change was observed between groups (p>0.54). The pH did not change during the 3×15 application technique; however, all acidic bleaching gels significantly decreased in pH when applied for 1×45 (p<0.01). CONCLUSIONS: The amount of HP that reaches the pulp chamber was lower when neutral/alkaline pH gels were used, independently of the application technique. When considering acidic pH gels, it is preferable to use the 3×15 application technique, mainly because longer application time (1×45) results in lower pH. No difference was observed between groups with regards to color change.

Vitamin D deficiency in solid-organ transplant recipients from a Spanish Mediterranean population.

BACKGROUND: Solid-organ transplant recipients (SOTRs) are at risk of developing vitamin D deficiency, mainly caused by reduced sunlight exposure with subsequent low vitamin D synthesis in the skin. AIM: To analyse whether SOTRs from a Spanish Mediterranean region were vitamin D-deficient. METHODS: This was a cross-sectional, descriptive and observational study in a transplantation-specialized Dermatological Unit from a Mediterranean area to determine the calcidiol levels of a cohort of 78 consecutively attending patients not receiving vitamin D supplements. Serum 25(OH)D3 levels were determined and clinical characteristics were collected. Logistic regression analysis was used to analyse variables associated with dichotomized 25(OH)D3 levels (≤ or > 10 ng/mL). RESULTS: The cohort comprised 30 lung, 29 kidney and 19 liver transplant recipients. Mean calcidiol was 18 ± 9 ng/mL. Deficiency of 25(OH)D3 was present in 19% of patients, while 68% had insufficient levels and 13% had sufficient levels. Following multivariate logistic regression analysis, the season of blood sampling remained the only predictor of deficient 25(OH)D3 levels. CONCLUSION: Despite living in a mid-latitude country with sunny weather, our SOTR population was at high risk of developing hypovitaminosis D, especially in autumn/winter. Avoiding sun exposure is important to prevent skin cancer, but careful monitoring of vitamin D status is recommended, with supplementation if hypovitaminosis D is detected.

Imatinib: una nueva herramienta para el manejo de la enfermedad del injerto contra el hospedador crónica esclerodermiforme / Imatinib: A New Tool for the Management of Chronic Sclerodermatous Graft-Vs-Host Disease

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Prevalence of Actinic Keratosis in Different Regions of Spain: The EPIQA Study / Prevalencia de la queratosis actínica en diferentes regiones españolas: estudio EPIQA

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Bank vole immunoheterogeneity may limit Nephropatia Epidemica emergence in a French non-endemic region.

Ecoevolutionary processes affecting hosts, vectors and pathogens are important drivers of zoonotic disease emergence. In this study, we focused on nephropathia epidemica (NE), which is caused by Puumala hantavirus (PUUV) whose natural reservoir is the bank vole, Myodes glareolus. We questioned the possibility of NE emergence in a French region that is considered to be NE-free but that is adjacent to a NE-endemic region. We first confirmed the epidemiology of these two regions and we demonstrated the absence of spatial barriers that could have limited dispersal, and consequently, the spread of PUUV into the NE-free region. We next tested whether regional immunoheterogeneity could impact PUUV chances to circulate and persist in the NE-free region. We showed that bank voles from the NE-free region were sensitive to experimental PUUV infection. We observed high levels of immunoheterogeneity between individuals and also between regions. Antiviral gene expression (Tnf and Mx2) reached higher levels in bank voles from the NE-free region. During experimental infections, anti-PUUV antibody production was higher in bank voles from the NE-endemic region. These results indicated a lower susceptibility to PUUV for bank voles from this NE-free region, which might limit PUUV persistence and therefore, the risk of NE.

Serum YB-1 (Y-box binding protein 1) as a biomarker of bone disease progression in patients with breast cancer and bone metastases.

YB-1 (Y-box binding protein 1) is a multifunctional cold-shock protein that has been implicated in all hallmarks of cancer. Elevated YB-1 protein level was associated with poor prognosis in several types of cancers, including breast cancer (BC), where it is a marker of decreased overall survival (OS) and distant metastasis-free survival across all subtypes. YB-1 is also secreted by different cell types and may act as an extracellular mitogen; however the pathological implications of the secreted form of YB-1 (sYB-1) are unknown. Our purpose was to retrospectively evaluate the association between YB-1 measured by ELISA in serum and disease characteristics and outcomes in patients with BC and bone metastases (BM). In our cohort, sYB-1 was detected in the serum of 22 (50%) patients, and was associated with the presence of extra-bone metastases (p=0.044). Positive sYB-1 was also associated with faster bone disease progression (HR 3.1, 95% CI 1.09-8.95, P=0.033), but no significant differences were observed concerning OS, and time to development of skeletal-related events. Moreover, patients with positive sYB-1 also had higher levels of IL-6, a known osteoclastogenic inducer. Therefore, detection of sYB-1 in patients with BC and BM may indicate a higher tumor burden, in bone and extra-bone locations, and is a biomarker of faster bone disease progression.

Precáncer cutáneo / Precancerous skin lesions

Bajo el término de precáncer cutáneo se han englobado tradicionalmente distintas entidades, clínica e histológicamente reconocibles, asociadas a un cierto riesgo de evolución a carcinoma escamoso cutáneo invasivo aunque en la actualidad se tiende a interpretarlas como carcinomas in situ. En este documento de consenso se abordan distintos aspectos de estas lesiones como son su evaluación a través de las características clínicas e, histopatológicas de las mismas, la evaluación inicial del paciente afecto, la identificación de los factores de riesgo para su desarrollo, los distintos métodos hoy día existentes para su estudio y diagnóstico así como las diferentes estrategias terapéuticas

Certain clinically and histologically recognizable skin lesions with a degree of risk of progression to squamous cell carcinoma have been traditionally grouped as precancerous skin conditions but now tend to be classified as in situ carcinomas. This consensus statement discusses various aspects of these lesions: their evaluation by means of clinical and histopathologic features, the initial evaluation of the patient, the identification of risk factors for progression, and the diagnostic and treatment strategies available today

Precancerous Skin Lesions. / Precáncer cutáneo.

Certain clinically and histologically recognizable skin lesions with a degree of risk of progression to squamous cell carcinoma have been traditionally grouped as precancerous skin conditions but now tend to be classified as in situ carcinomas. This consensus statement discusses various aspects of these lesions: their evaluation by means of clinical and histopathologic features, the initial evaluation of the patient, the identification of risk factors for progression, and the diagnostic and treatment strategies available today.

Tumoración cutánea pulsátil supraclavicular / Pulsatile Supraclavicular Skin Tumor

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Significado del afrontamiento familiar para enfermeras de unidades de cuidados intensivos de adultos de Medellín / Meaning of family confrontation for nurses of intensive care units for adult people - Medellín 2013

Objetivo: Comprender el significado que le dan las enfermeras a partir de sus experiencias al afrontamiento familiar durante la hospitalización del paciente en las unidades de cuidados intensivos de adultos de Medellín. Método: Se realizó una investigación de tipo cualitativa con un enfoque fenomenológico, se utilizó muestreo teórico, según criterios de conveniencia. Se realizaron entrevistas con preguntas abiertas a enfermeras que trabajaban en diferentes unidades de cuidados intensivos de adultos de la ciudad de Medellín, con más de un año de experiencia en dichas unidades. Para el análisis se codificó y categorizó la información y se elaboraron mapas conceptuales para el informe final. Resultados: Esta investigación evidenció que las enfermeras brindan un cuidado directo al paciente en las unidades de cuidados intensivos según su situación de gravedad y posteriormente ofrecen cuidados a sus familias; respecto al afrontamiento, las enfermeras consideran que la familia logra un afrontamiento de la situación cuando comprende los procesos que se desarrollaran en las unidades de cuidados intensivos y pueden aportar al cuidado del paciente, mientras que las familias que no afrontan se debe a que no entienden el proceso, se encuentran desesperadas o están ausentes. Y por último, las intervenciones que las enfermeras consideran que se deben realizar para favorecer el afrontamiento familiar son dar información, el apoyo interdisciplinario, permitir las visitas y el acompañamiento. Conclusión: El afrontamiento familiar para las enfermeras significa que la familia entienda, comprenda, acepte, conozca, asuma, se someta, sobrelleve la situación y por consiguiente tome buenas decisiones para el cuidado del paciente en las unidades de cuidados intensivos adulto

Objective: To comprehend the meaning nurses give to family confrontation, from their experiences while patients are in adult intensive care units in Medellin 2013. Method: A qualitative research study was carried out using a phenomenological approach and theoretical convenience sampling of subjects was used. Interviews with open questions were conducted with nurses that worked in different intensive care units in the city of Medellin, with more than one year of experience in these units. The information was coded and categorised to perform the analysis, and some concept maps were created for the final report. Results: This study showed that nurses focus their care on the critical patient and not on the patient's family. They considered that there is family confrontation when its members comprehend the processes that are carried out in the intensive care unit, and can contribute to the patient's care, while if families do not have confrontations, it is because they do not understand the process, or feel desperate or are absent. The interventions that nurses consider must be done to help in the family confrontation are: information, interdisciplinary support, visits, and companionship. Conclusion: For the nurses, family confrontation means that family members understand, comprehend, accept, know, bear and go on with the situation; therefore, they can make good decisions regarding the patient's care in the adult intensive care units