Intravascular Myopericytoma of the Plantar Region: Case Report and Discussion of the Probable Origin From a Cutaneous Vascular Malformation.

Myopericytoma is a perivascular myoid neoplasm of skin and soft tissues characterized by numerous thin-walled blood vessels surrounded concentrically by round to spindle myoid tumor cells, which shows α-smooth muscle actin and h-caldesmon coexpression and commonly negativity for desmin. These tumors arise predominantly in extremities of adult patients with benign clinical course. Based on the architectural pattern, there are various histologic variants as classical-solid myopericytoma, hemangiopericytoma-like myopericytoma, angioleiomyoma-like myopericytoma, myofibroma-like myopericytoma, hipocelular fibroma-like myopericytoma, intravascular myopericytoma, cellular immature myopericytoma, and malignant myopericytoma. The authors report a case that fully satisfies the morphological and immunohistochemical criteria for intravascular myopericytoma, which plantar location is not previously described in the literature. In addition, the authors discuss about its possible development from a preexistent cutaneous vascular malformation.

DECKO: Single-oligo, dual-CRISPR deletion of genomic elements including long non-coding RNAs.

BACKGROUND: CRISPR genome-editing technology makes it possible to quickly and cheaply delete non-protein-coding regulatory elements. We present a vector system adapted for this purpose called DECKO (Double Excision CRISPR Knockout), which applies a simple two-step cloning to generate lentiviral vectors expressing two guide RNAs (gRNAs) simultaneously. The key feature of DECKO is its use of a single 165 bp starting oligonucleotide carrying the variable sequences of both gRNAs, making it fully scalable from single-locus studies to complex library cloning. RESULTS: We apply DECKO to deleting the promoters of one protein-coding gene and two oncogenic lncRNAs, UCA1 and the highly-expressed MALAT1, focus of many previous studies employing RNA interference approaches. DECKO successfully deleted genomic fragments ranging in size from 100 to 3000 bp in four human cell lines. Using a clone-derivation workflow lasting approximately 20 days, we obtained 9 homozygous and 17 heterozygous promoter knockouts in three human cell lines. Frequent target region inversions were observed. These clones have reductions in steady-state MALAT1 RNA levels of up to 98 % and display reduced proliferation rates. CONCLUSIONS: We present a dual CRISPR tool, DECKO, which is cloned using a single starting oligonucleotide, thereby affording simplicity and scalability to CRISPR knockout studies of non-coding genomic elements, including long non-coding RNAs.

Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report.

BACKGROUND: Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the BRAF gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature. CASE PRESENTATION: Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the V600E (T1799A) mutation was detected in exon 15 of the BRAF gene. CONCLUSION: Since fistulae experience persistent inflammation, the fact that this melanoma harbours a BRAF mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of BRAF gene mutations.

Rare Site Hepatocellular Carcinoma Metastasis.

INTRODUCTION: Besides more common sites such as lung or peritoneum, hepatocellular carcinoma (HCC) can metastatize to rare sites. We report herein a new metastatic site of HCC: the nail-bed. We also review other recently reported rare site HCC metastases (RSHM). CASE REPORT: A 66-year-old woman with a 12-year history of resected-stage IA HCC who later presented lung, spleen and brain metastases treated with surgery, systemic therapies (sorafenib, sunitinib, capecitabine) and radiotherapy. The patient was referred to us because of a painful and rapidly evolving mass in the nail-bed of the left thumb. Biopsy confirmed nail-bed HCC metastasis, and the finger was amputated. The patient died few weeks later. CONCLUSION: This case was an opportunity for us to review RSHM. This type of metastasis seems to be an early event, in the context of advanced stage HCC with elevated protein induced by vitamin K absence-II (PIVKA II). The Lee nomogram is useful in detecting patients at high risk of developing RSHM. We would suggest insisting on systemic treatment in these metastatic patients although overall survival after RSHM diagnosis is poor.

Hacking the Cancer Genome: Profiling Therapeutically Actionable Long Non-coding RNAs Using CRISPR-Cas9 Screening.

Long non-coding RNAs (lncRNAs) represent a huge reservoir of potential cancer targets. Such "onco-lncRNAs" have resisted traditional RNAi methods, but CRISPR-Cas9 genome editing now promises functional screens at high throughput and low cost. The unique biology of lncRNAs demands screening strategies distinct from protein-coding genes. The first such screens have identified hundreds of onco-lncRNAs promoting cell proliferation and drug resistance. Ongoing developments will further improve screen performance and translational relevance. This Review aims to highlight the potential of CRISPR screening technology for discovering new onco-lncRNAs, and to guide molecular oncologists wishing to apply it to their cancer of interest.

Role of community pharmacists in skin cancer screening: A descriptive study of skin cancer risk factors prevalence and photoprotection habits in Barcelona, Catalonia, Spain.

BACKGROUND: Skin cancer incidence is increasing alarmingly, despite current efforts trying to improve its early detection. Community pharmacists have proven success in implementing screening protocols for a number of diseases because of their skills and easy access. OBJECTIVE: To evaluate the prevalence of skin cancer risk factors and the photoprotection habits with a questionnaire in community pharmacy users. METHODS: A research group consisting of pharmacists and dermatologists conducted a descriptive cross-sectional study to assess photoprotection habits and skin cancer risk factors by using a validated questionnaire in 218 community pharmacies in Barcelona from May 23rd to June 13th 2016. All participants received health education on photoprotection and skin cancer prevention. Patients with ≥1 skin cancer risk factor were referred to their physician, as they needed further screening of skin cancer. RESULTS: A total of 5,530 participants were evaluated. Of those, only 20.2% participants had received a total body skin examination for skin cancer screening in the past by a physician and 57.1% reported using a SPF 50+ sunscreen. 53.9% participants presented ≥1 skin cancer risk factor: 11.8% participants reported having skin cancer familial history and 6.2% reported skin cancer personal history; pharmacists found ≥10 melanocytic nevi in 43.8% participants and chronically sun-damaged skin in 21.4%. Lesions suspicious for melanoma were reported in 10.9% of the participants and urgent dermatological evaluation was recommended. CONCLUSIONS: Pharmacists can detect people with skin cancer risk factors amongst their users. This intervention can be considered in multidisciplinary strategies of skin cancer screening.

[Use of urine drug screening in the emergency department of a paediatric hospital]. / Utilidad de las técnicas de cribado de tóxicos en orina solicitadas desde el servicio de urgencias de un hospital pediátrico.

OBJECTIVE: To describe the situations in which urine drug screening is used in a Paediatric Emergency Department (ED). An analysis is also made on its potential usefulness on whether it changes the patient management, and if the results are confirmed by using specific techniques. METHODOLOGY: A retrospective study was conducted on patients under the age of 18 attended in the ED during 2014 and in whom urine drug screening was requested. Depending on the potential capacity of the screening result to change patient management, two groups were defined (potentially useful and not potentially useful). RESULTS: Urine drug screening was performed on a total of 161 patients. The screening was considered not to be potentially useful in 87 (54.0%). This was because the clinical history already explained the symptoms the patient had in 55 (34.1%) patients, in 29 (18.0%) because the patient was asymptomatic, and in 3 (1.9%) because the suspected drug was not detectable in the screening. The drug screening results changed the patient management in 5 (3.1%) cases. A toxic substance was detected in 44 (27.3%). Two out of the 44 that were positive (2.1%) were re-tested by specific techniques, and presence of the toxic substance was ruled out in both of them (false positives). CONCLUSIONS: Most of the drug screening tests are not justified, and it is very infrequent that they change patient management. It is very rare that the results are confirmed using more specific methods. Urine drug screening tests should be restricted to particular cases and if the result has legal implications, or if the patient denies using the drug, it should be followed by a specific toxicological study to provide a conclusive result.

[Repeated poisoning episodes: Alarm sign of risk situations]. / Episodios repetidos de intoxicación: signo de alarma de situaciones de riesgo.

INTRODUCTION: Prevention is an essential aspect in paediatric poisonings, especially when recurrent episodes are detected. The aims of this article are to detect the recurrence rate for suspected poisoning in emergency consultations, as well as to identify the cases in which specific preventive measures are indicated, and to determine whether the creation of a specific item for recurrent episodes in the computerised medical records system facilitates its detection. MATERIAL AND METHODS: A retrospective study was conducted on patients less than 18 years of age treated in the emergency room due to suspected poisoning during 2013 and 2014. Patients were divided according to the presence or absence of previous episodes. From January 2014, a specific item is present in the computerised medical records of the poisoned patient, where the history of previous episodes is registered. The preventive measures used between both groups were compared. RESULTS: A total of 731 consultations were recorded for suspected poisoning. A history of previous episodes was detected in 9% of cases. Medical injury reports and follow-up in outpatient clinics were more often performed in patients with recurrent episodes than in patients without them (28.8% vs 18.0%, P=.034, and 65.2% vs. 18.8%, P<.001, respectively). In 2013, the recurrence rate was 5.9% vs 12% in 2014 (P=.004). CONCLUSIONS: The recurrence rate observed is significant. Although preventive measures are more frequently indicated in these patients, their application is low. The creation of a specific item for recurrent episodes in a computerised medical records system facilitates their detection.

[Impact of quality-indicator-based measures to improve the treatment of acute poisoning in pediatric emergency patients]. / Impacto de acciones de mejora desarrolladas a partir de indicadores de calidad en el tratamiento de las intoxicaciones agudas pediátricas.

OBJECTIVES: To analyze the impact of quality-indicator-based measures for improving quality of care for acute poisoning in pediatric emergency departments. MATERIAL AND METHODS: Recent assessments of quality indicators were compared with benchmark targets and with results from previous studies. The first study evaluated 6 basic indicators in the pediatric emergency departments of members of to the working group on poisoning of the Spanish Society of Pediatric Emergency Medicine (GTI-SEUP). The second study evaluated 20 indicators in a single emergency department of GTI-SEUP members. Based on the results of those studies, the departments implemented the following corrective measures: creation of a team for gastric lavage follow-up, preparation of a new GTI-SEUP manual on poisoning, implementation of a protocol for poisoning incidents, and creation of specific poisoning-related fields for computerized patient records. RESULTS: The benchmark targets were reached on 4 quality indicators in the first study. Improvements were seen in the availability of protocols, as indicators exceeded the target in all the pediatric emergency departments (vs 29.2% of the departments in an earlier study, P < .001). No other significant improvements were observed. In the second study the benchmarks were reached on 13 indicators. Improvements were seen in compliance with incident reporting to the police (recently, 44.4% vs 19.2% previously, P = .036), case registration in the minimum basic data set (51.0% vs 1.9%, P < .001), and a trend toward increased administration of activated carbon within 2 hours (93.1% vs 83.5%, P = .099). No other significant improvements were seen. CONCLUSION: The corrective measures led to improvements in some quality indicators. There is still room for improvement in these emergency departamens' care of pediatric poisoning.

OBJETIVO: Analizar el impacto de la aplicación de medidas de mejora implementadas a partir de la evaluación de indicadores de calidad (IC) en la atención prestada a los pacientes pediátricos con intoxicación aguda. METODO: Se compara el resultado actual de los IC con el estándar deseado y con el resultado obtenido en dos estudios previos. Estudio-1: evaluación de 6 IC básicos en los servicios de urgencias pediátricas (SUP) participantes en el Grupo de Trabajo de Intoxicaciones de la Sociedad Española de Urgencias Pediátricas (GTI-SEUP). Estudio-2: evaluación de los 20 IC en uno de los servicios de urgencias del GTI-SEUP. Tras la realización de los mismos se implementaron medidas correctoras: grupo de seguimiento de lavado gástrico, reedición del manual de intoxicaciones del GTI-SEUP, implementación del protocolo de atención al paciente intoxicado y creación de campos específicos en la historia clínica informatizada. RESULTADOS: Estudio-1: se alcanza el estándar en 4 IC y mejora la disponibilidad de protocolos (el IC supera el estándar en el 100% de SUP vs el 29,2% previo; p < 0,001) sin cambios significativos en el resto de IC. Estudio-2: se alcanza el estándar en 13 IC y mejora de los IC sobre cumplimentación de parte judicial (44,4% vs 19,2%; p = 0,036), registro del Conjunto Mínimo de Datos (51,0% vs 1,9%; p < 0,001) y tendencia al aumento de administración de carbón activado en las primeras 2 horas (93,1% vs 83,5%; p = 0,099). No existen cambios significativos en el resto de IC. CONCLUSIONES: La implementación de medidas correctoras ha dado lugar a una mejora en el resultado de algunos IC. La calidad de la asistencia de estos pacientes es aún mejorable.

The accuracy and reproducibility of the endometrial receptivity array is superior to histology as a diagnostic method for endometrial receptivity.

OBJECTIVE: To compare the accuracy and reproducibility of the endometrial receptivity array (ERA) versus standard histologic methods. DESIGN: A comparative prospective study (May 2008-May 2012). SETTING: University-affiliated infertility clinic. PATIENT(S): Eighty-six healthy oocyte donors, regularly cycling, aged 20-34 years with a body mass index (BMI) of 19-25 kg/m(2). INTERVENTION(S): Endometrial biopsies were collected throughout the menstrual cycle. For the accuracy study, 79 samples were grouped into two cohorts: the training set (n = 79) for ERA machine-learning training and dating, and a dating subset (n = 49) for comparison between histologic and ERA dating. For the reproducibility study, seven women underwent ERA testing and it was repeated in the same patients on the same day of their cycle 29-40 months later. MAIN OUTCOME MEASURE(S): Concordance of histologic and ERA dating related to LH as a reference, and interobserver variability between pathologists were statistically analyzed by the quadratic weighted Kappa index. The ERA reproducibility was tested and its gene expression visualized by principal component analysis. RESULT(S): For each pathologist, concordance against LH peak yielded values of 0.618 (0.446-0.791) and 0.685 (0.545-0.824). Interobserver variability between pathologists yielded a Kappa index of 0.622 (0.435-0.839). Concordance for ERA dating against LH peak showed a value of 0.922 (0.815-1.000). Reproducibility of the ERA test was 100% consistent. CONCLUSION(S): The ERA is more accurate than histologic dating and is a completely reproducible method for the diagnosis of endometrial dating and receptivity status.