MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin.

Epithelial to mesenchymal transition (EMT) is an important mechanism of invasion in cutaneous squamous cell carcinomas (cSCCs) and has been found to be enhanced in tumors originated from actinic keratosis with transformation limited to the basal epithelial layer -differentiated pathway-, compared to cases with invasion subsequent to complete epidermal transformation -classical pathway-. Several microRNAs and proteins can contribute to EMT modulation in cSCCs. MicroRNA21 and microRNA31 are involved in posttranscriptional regulation of protein expression and could play a relevant role in EMT and cSCC progression. Throughout the EMT process upregulation of matrix metalloproteinases (MMPs) enhances invasiveness and MMP-1 and MMP-3 contribute to local invasion, angiogenesis and metastasis in cSCCs. Additionally, cSCC development is associated with PTEN loss and NF-κB, NOTCH-1 and p63 activation. The aim of this work is to identify differences in the expression of those molecules between both pathways of cSCCs development. Eight tissue microarrays from 80 consecutive cSCCs were analyzed using LNA-based miRNA in situ hybridization for miRNA21 and miRNA31 evaluation, and immunohistochemistry for MMP-1, MMP-3, PTEN, NOTCH-1, NF-κB, p63 and CD31. Significantly higher expression of miRNA31 (p < 0.0001) and MMP-1 (p = 0.0072) and angiogenesis (p = 0.0199) were found in the differentiated pathway, whereas PTEN loss (p = 0.0430) was more marked in the classical pathway. No significant differences were found for the other markers. Our findings support a contribution of miRNA31 and MMP-1 in the differentiated pathway, associated to EMT and increased microvascularization. The greater PTEN loss in the classical pathway indicate that its relevance in cSCC is not EMT-related.

[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.

Knowledge based recursive non-linear partial least squares (RNPLS).

Soft sensors driven by data are very common in industrial plants to perform indirect measurements of difficult to measure critical variables by using other variables that are relatively easier to obtain. The use of soft sensors implies some challenges, such as the colinearity of the predictor variables, the time-varying and possible non-linear nature of the industrial process. To deal with the first challenge, the partial least square (PLS) regression has been employed in many applications to model the linear relations between process variables, with noisy and highly correlated data. However, the PLS model needs to deal with the other two issues: the non-linear and time-varying characteristics of the processes. In this work, a new knowledge-based methodology for a recursive non-linear PLS algorithm (RNPLS) is systematized to deal with these issues. Here, the non-linear PLS algorithm is set up by carrying out the PLS regression over the augmented input matrix, which includes knowledge based non-linear transformations of some of the variables. This transformation depends on the system's nature, and takes into account the available knowledge about the process, which is provided by expert knowledge or emulated using software tools. Then, the recursive exponential weighted PLS is used to modify and adapt the model according to the process changes. This RNPLS algorithm has been tested using two case studies according to the available knowledge, a real industrial evaporation station of the sugar industry, where the expert knowledge about the process permits the formulation of the relationships, and a simulated wastewater treatment plant, where the necessary knowledge about the process is obtained by a software tool. The results show that the methodology involving knowledge regarding the process is able to adjust the process changes, providing highly accurate predictions.

Phototoxic reaction to a combined oral contraceptive (levonorgestrel/ethinylestradiol).

We present the case of a phototoxic skin reaction due to the regular intake of a combined oral contraceptive (levonorgestrel/ethinylestradiol). Upon spectrophotometer testing, we demonstrated high absorption in the UV-B region of the solar spectrum of the combined product (Ovoplex®), especially for the estrogen compound (ethinylestradiol).

Análisis de técnica anestésica para aspiración folicular transvaginal en Embriovid Centro de Reproducción Asistida / Technical analysis for anesthesia in vacuum follicular transvaginal Embriovid center of assisted reproduction

OBJETIVO: Analizar las técnicas anestésicas utilizadas en el centro de reproducción asistida avanzada Embriovid para la aspiración folicular transvaginal guiada por ecografía (AFT) con el propósito de estandarizar las dosis de anestésicos ,revisar sus complicaciones y el perfil de recuperación en pacientes donantes y en tratamiento de fertilidad. DISEÑO METODOLÓGICO: Serie de casos. Población y temporalidad: pacientes sometidas a AFT bajo anestesia en el centro de alta especialidad de reproducción asistida Embriovid en la ciudad de La Paz- Bolivia en el periodo de Septiembre 2015 a Abril 2016. MATERIAL Y MÉTODO: Se revisaron los expedientes clínicos de pacientes sometidas a anestesia para AFT y se registraron variables biodemograficas, los datos de recuperación y complicaciones. Las pacientes recibieron anestesia total intravenosa TIVA en bolos con propofol y fentanil o en su defecto sedación consiente con fentanil y midazolam o dosis bajas de propofol. Se registraron los datos de la hoja anestésica con dosis totales, tiempos quirúrgicos y anestésicos, y medicamentos no anestésicos administrados. RESULTADOS: Se incluyeron 209 procedimientos divididos en dos grupos de registro, grupo 1 de donantes con 91 aspiraciones (43.5%) y grupo 2 con 118 aspiraciones (56.5%) de pacientes en tratamiento de fertilidad (óvulos propios). 199 pacientes (94.7%) recibieron anestesia TIVA en bolos y 10 pacientes sedación consiente (5.3%). La técnica TIVA combino fentanil con propofol en bolos. La dosis de fentanil fue similar en ambos grupos (promedio 0.1mg) mientras que la dosis de propofol fue mayor en el grupo 1(200mg vs. 180mg) .La técnica TIVA presento periodos de apnea cortos que no requirió maniobras invasivas. El dolor postoperatorio fue frecuente pero de baja intensidad. El tiempo de estadía de las pacientes conservo su carácter ambulatorio. CONCLUSIONES: La técnica TIVA en bolos que combina propofol con fentanil parece ser una técnica anestésica segura en manos de un anestesiólogo y adecuada para la aspiración transvaginal de folículos ováricos.

OBJECTIVE: To analyze the anesthetic techniques used in the center of advanced assisted reproduction Embriovid for transvaginal follicular aspiration guided by ultrasound (TFA) in order to standardize the dose of anesthetic, review it's complications and recovery profile in donor patients in fertility treatment. METHODOLOGICAL DESIGN: Case series. Population and temporality: Patients under anesthesia for TFA in the center of highly specialized assisted reproduction "Embriovid" in the city of La Paz, Bolivia in the period September 2015 to April 2016. MATERIAL AND METHODS: Clinical records of patients undergoing anesthesia for TFA, their biodemographic variables, data of recovery and complications were recorded and reviewed. Patients received total intravenous anesthesia (TIVA) with with bolus of propofol and fentanyl or conscious sedation with fentanyl and midazolam or low doses of propofol. We record the anesthetic dose, surgical and anesthesia times, and no anesthetic drugs administered. RESULTS: 209 procedures divided into two groups registration, group 1 donors aspirations 91 (43.5%) and Group 2 with 118 aspirations (56.5%) of patients in fertility treatment (own oocytes) were included. 199 patients (94.7%) received bolus TIVA anesthesia and conscious sedation in 10 patients (5.3%). TIVA technique combine with propofol bolus fentanyl. The dose of fentanyl was similar in both (average 0.1mg) groups while propofol dose was higher in Group 1 TIVA (200mg vs. 180mg). The TIVA technique shows periods of apnea not requiring invasive procedures. Postoperative pain was frequent but low intensity. The length of stay of patients retained its outpatient basis. CONCLUSIONS: TIVA bowling technique combining propofol with fentanyl appears to be a safe anesthetic technique in the hands of an anesthesiologist and suitable for transvaginal aspiration of ovarian follicles.

[Tinea capitis in elderly women: a report of 4 cases]. / Tinea capitis en mujeres de edad avanzada: descripción de 4 casos.

Tinea capitis is a condition usually found only in children. However, its epidemiological profile has changed in recent decades, with regard to age at onset and the causative microorganisms. We report the cases of 4 women over 65 years of age diagnosed with tinea capitis. One presented plaques of alopecia with desquamation and the other 3 developed crusted inflammatory lesions. Cultures were positive for Trichophyton tonsurans (2 patients), Trichophyton rubrum, and Trichophyton mentagrophytes. The relative rarity of tinea capitis in the elderly and the frequently atypical presentation in this age group can delay diagnosis, leading to irreversible sequelae and increasing the risk of contagion. Fungal culture should be included in the study of persistent, atypical dermatoses of the scalp, particularly in the elderly.

Postoperative pyoderma gangrenosum: diagnostic value of 16s ribosomal RNA sequencing and review of the literature.

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon condition, but can lead to the diagnosis of an underlying systemic disease. It can appear spontaneously or as a result of the pathergy phenomenon after trauma or surgery. METHODS: We review three patients with postoperative PG (PPG) and the relevant literature. We also report an accurate method for microbial detection by 16S ribosomal (r)RNA sequencing. RESULTS: A 47-year-old woman and two men aged 54 and 48 years, respectively, presented with sterile ulcerations after surgery. Associated conditions (Crohn's disease and leukaemia) were present. Surgical wound infection was suspected and systemic empirical antibiotics were prescribed. After infection was excluded, PPG was diagnosed and corticosteroids were started. DISCUSSION: PPG should be considered in the differential diagnosis of postsurgical wound complications. Recognition of this condition may prevent unnecessary administration of antimicrobial treatment and development of more extensive ulcerations. It may also be the clue for the diagnosis of an underlying systemic disease. We discuss the usefulness of 16S rRNA sequencing for microbial detection and identification in order to exclude a causative infection in patients who have previously received antibiotic treatment.

A prospective study of the incidence of skin cancer and its risk factors in a Spanish Mediterranean population of kidney transplant recipients.

BACKGROUND: Skin cancer is the most common malignancy occurring in kidney transplant recipients (KTRs). OBJECTIVES: Our purpose was to investigate, prospectively, the cumulative incidence of cancerous and precancerous skin lesions as well as their risk factors in a close follow-up population of KTRs from a Mediterranean area of Spain. PATIENTS AND METHODS: One hundred and seventy-four consecutive KTRs were examined at the moment of transplant and then at 6-month intervals. The cumulative incidence of skin cancer was computed. To analyse the role of potential risk factors (age at transplantation, cause of renal failure, duration of pretransplant dialysis, type of immunosuppressive regimen, sun-reactive skin type and history of occupational sun exposure), the Cox regression method was used. RESULTS: After a median follow-up of 72 months (range, 12-140), 39 patients (25.3%) developed 142 tumours [84 basal cell carcinoma (BCC) and 58 squamous cell carcinoma (SCC)]. The BCC/SCC ratio was 1.4 : 1. The cumulative incidence for skin cancer was 13% after 3 years of graft survival, increasing to 27.5% at 6 years and 48% at 10 years. Only age at the time of transplantation and occupational sun exposure had statistical significance as risk factors (P < 0.001). CONCLUSIONS: Our study confirms the high incidence of non-melanoma skin cancer among KTRs in a Mediterranean population with occupational sun exposure and the patient's age at the time of transplantation being the main risk factors. We believe that all organ transplant programs should provide educational information about protecting oneself from the sun as well as include follow-up visits by dermatologists in order to facilitate early diagnosis and treatment of skin cancer.

p53 immunohistochemical expression in early posttransplant-associated malignant and premalignant cutaneous lesions.

BACKGROUND: Current evidence suggests that p53 accumulation is critical to the development of skin cancer in the general population. It is possible, however, that the molecular steps involved in transplant-associated and non-transplant-associated skin carcinogenesis may differ. OBJECTIVE: Our purpose was to examine p53 expression in premalignant and malignant skin lesions from renal transplant recipients (RTRs) in their first 3 years of immunosuppression, as well as in equivalent lesions from immunocompetent normal individuals. METHODS: p53 expression was examined by routine immunohistochemical methods using the anti-p53 monoclonal antibody DO7. RESULTS: p53 immunoreactivity was more prevalent in dysplastic epidermal keratoses and cutaneous carcinomas from RTRs than in equivalent lesions from nontransplant controls. Statistical analysis revealed significant differences, however, only in premalignant skin lesions (p = 0.03). CONCLUSION: This study demonstrates that accumulation of p53 protein is frequently encountered in both premalignant and malignant skin lesions of RTRs, and that this may occur as an early step in transplant-associated skin carcinogenesis.

Hereditary hypotrichosis simplex.

Hypotrichosis is a relatively common feature of a number of complex hereditary syndromes. However, the isolated variant, called hereditary hypotrichosis simplex (HHS), is especially uncommon. We present a Spanish family with 8 of 19 persons covering 4 generations affected by HHS. No associated ectodermal or other defects were noted. The pedigree was compatible with an autosomal dominant inheritance with variable penetrance.

Low-grade mucoepidermoid carcinoma on the vermilion border of the lip.

We report a case of primary cutaneous carcinoma with mucoepidermoid features located on the vermilion border of the lower lip, at a distance from both salivary glands and cutaneous adnexal structures. The clinical appearance of the present case, which is similar to that of conventional cutaneous squamous cell carcinoma, as well as the existence of surrounding areas of actinic cheilitis favors the hypothesis of a phenomenon of mucinous metaplastic change in a squamous cell carcinoma. We consider that, independently of their origin, tumors having mucin-secreting and squamous differentiation ought to be named according to the same criteria generally used for other organs, namely, "low grade mucoepidermoid carcinoma" would designate tumors with bland mucin-secreting cells and well-differentiated squamous component, and "high grade mucoepidermoid carcinoma" would indicate their less well differentiated counterpart. We propose to reserve the term "adenosquamous carcinoma" for aggressive tumors with high-grade glandular and squamous elements, marked nuclear atypia, frequent mitoses, and extensive necrosis.

CD44 distribution in sweat gland tumors suggests it has different functional roles in the various cell types.

CD44 is a polymorphic group of membrane glycoproteins with multiple functions that include cell adhesion. Since on normal sweat glands CD44 is expressed only in eccrine coil secretory cells, it has been considered as a possible marker of this type of differentiation. We have immunohistochemically investigated the distribution of CD44 in paraffin-embedded samples of 41 benign and malignant sweat gland tumors by using a monoclonal antibody directed against the standard isoform of CD44. CD44 was strongly expressed in epithelial cells at the peripheral row of syringomas and in cuticular areas of eccrine poromas. Apocrine tumors such as apocrine hidrocystoma, syringocystadenoma papilliferum, or hidradenoma papilliferum showed intense CD44 positivity in the portion of cells in contact with the neighboring stroma and focally on the luminal side of cells with apocrine secretion. Cylindromas and spiradenomas presented focal CD44 positivity, virtually limited to clear cells. Malignant neoplasms exhibited irregular CD44 staining, which was more intense in the less differentiated zones and tumors. Our results indicate that CD44 is not a useful marker for a specific form of sweat gland differentiation. Nevertheless, its characteristic patterns of distribution might reflect the variety of functional roles assumed by the different CD44 isoforms in each epithelial cell.