[Ethics of care: Assessment of the ethical issues in the protocols or consensuses on mechanical restraint in force in Spain]. / Ética de los cuidados: valoración de los contenidos éticos en los protocolos o consensos de contención mecánica vigentes en España.

INTRODUCTION: Mechanical restraints are widely used in health care practice, despite the numerous ethical conflicts they raise. The aim of this study is to evaluate the ethical considerations contemplated in the current protocols on mechanical restraint in Spain. METHOD: Systematic review in PubMed, WOS and Scopus, Google and Google Scholar. An ad hoc list of 30 items was used to evaluate the ethical content of the protocols. The quality of guidelines was assessed with AGREE II. RESULTS: The need for informed consent (IC) is reflected in 72% of the documents, the IC model sheet is included in only 41% of them, the rest of the analyzed characteristics on IC are fulfilled in percentages between 6% (the document includes the need to reevaluate the indication for IC) and 31% (the document contemplates to whom it should be requested). More than 20 ethical contents are reflected in 31% of them and less than 10 in 19% of the guidelines. The quality of the guides, according to AGREE II, ranged from 27 to 116 points (maximum possible 161), with a mean score of 68.7. Only 9% of the documents were classified as high quality. Finally, the correlation between ethical content and quality measured with AGREE II was 0.75. CONCLUSIONS: The variability of ethical contents in guidelines on mechanical restraints is very high. The ethical requirements to be included in protocols, consensus or Clinical Practice Guidelines should be defined.

Nutrition supplementation plus standard of care versus standard of care alone or standard of care plus unconditional cash transfer in the prevention of chronic malnutrition in Southern Angola: study protocol for the MuCCUA study, a cluster randomized controlled trial.

BACKGROUND: Chronic malnutrition is a condition associated with negative impacts on physical and cognitive development. It is multi-causal and can start very early in life, already in utero, thus it is especially challenging to find appropriate interventions to tackle it. The government of Angola is implementing a standard of care program with potential to prevent it, and the provision of cash transfers and the supplementation with small quantity lipid-based nutrients (SQ-LNS) are also promising interventions. We aimed to evaluate the impact of the standard of care program alone and of the standard of care plus a cash transfer intervention in the lineal growth of children less than 2 years old and compare it to the effectiveness of a nutrition supplementation plus standard of care program in Southern Angola. METHODS/DESIGN: The three-arm parallel cluster randomised controlled trial is set in four communes of Huila and Cunene provinces. Clusters are villages or neighbourhoods with a population around 1075 people. A total of twelve clusters were selected per arm and forty pregnant women are expected to be recruited in each cluster. Pregnant women receive the standard of care alone, or the standard of care plus unconditional cash transfer or plus nutritional supplementation during the first 1000 days, from pregnancy to the child reaching 24 months. The primary outcome is the prevalence of stunting measured as height-for-age Z-score (HAZ) < -2 in children below 2 years. Impact will be assessed at 3, 6, 12, 18 and 24 months of children's age. Secondary outcomes include mortality, morbidity, caring, hygiene and nutrition behaviours and practices, and women and children's dietary diversity. Quantitative data are also collected on women's empowerment, household food security, expenditure and relevant clinical and social events at baseline, endline and intermediate time points. DISCUSSION: The results will provide valuable information on the impact of the standard of care intervention alone as well as combined with an unconditional cash transfer intervention compared to a nutrition supplementation plus standard of care intervention, carried out during the first 1000 days, in the children´s growth up to 2 years and related outcomes in Southern Angola. TRIAL REGISTRATION: Clinical Trials NCT05571280. Registered 7 October 2022.

Co-enrichment of cancer-associated bacterial taxa is correlated with immune cell infiltrates in esophageal tumor tissue.

Esophageal carcinoma (ESCA) is a leading cause of cancer-related death worldwide, and certain oral and intestinal pathogens have been associated with cancer development and progression. We asked if esophageal microbiomes had shared alterations that could provide novel biomarkers for ESCA risk. We extracted DNA from tumor and non-tumor tissue of 212 patients in the NCI-MD case control study and sequenced the 16S rRNA gene (V3-4), with TCGA ESCA RNA-seq (n = 172) and WGS (n = 123) non-human reads used as validation. We identified four taxa, Campylobacter, Prevotella, Streptococcus, and Fusobacterium as highly enriched in esophageal cancer across all cohorts. Using SparCC, we discovered that Fusobacterium and Prevotella were also co-enriched across all cohorts. We then analyzed immune cell infiltration to determine if these dysbiotic taxa were associated with immune signatures. Using xCell to obtain predicted immune infiltrates, we identified a depletion of megakaryocyte-erythroid progenitor (MEP) cells in tumors with presence of any of the four taxa, along with enrichment of platelets in tumors with Campylobactor or Fusobacterium. Taken together, our results suggest that intratumoral presence of these co-occurring bacterial genera may confer tumor promoting immune alterations that allow disease progression in esophageal cancer.

A benchmark for Monte Carlo simulations in gamma-ray spectrometry Part II: True coincidence summing correction factors.

The goal of this study is to provide a benchmark for the use of Monte Carlo simulation when applied to coincidence summing corrections. The examples are based on simple geometries: two types of germanium detectors and four kinds of sources, to mimic eight typical measurement conditions. The coincidence corrective factors are computed for four radionuclides. The exercise input files and calculation results with practical recommendations are made available for new users on a dedicated webpage.

Effect of cannula insertion site in fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia on preterm premature rupture of membranes.

OBJECTIVE: Few fetal malformations benefit from in utero surgery. One of the major drawbacks of fetal surgery is preterm premature rupture of membranes (PPROM). Morbidity associated with congenital diaphragmatic hernia (CDH) is primarily respiratory but also gastrointestinal and induced prematurity are likely to worsens those complications. To assess whether or not the cannula insertion site on the maternal abdomen during fetoscopic endoluminal tracheal occlusion (FETO) was associated with PPROM before balloon removal. METHODS: This multicenter retrospective study was conducted on consecutive pregnancies with isolated left- or right-sided CDH fetuses who underwent FETO in 4 centers between January 2009 and January 2021. The insertion site for balloon insertion was categorized as above or below the umbilicus. One propensity score was analyzed in both groups: entry above the umbilicus and entry below, to calculate an average treatment effect (ATE) by inverse probability of treatment weighting (IPTW). Afterwards, one logistic regression and one Cox proportional hazard regression that included the ATE weights were performed to examine the effect size of entry point on the frequency and timing of PPROM prior to the balloon removal procedure. RESULTS: A total of 294 patients were included. Mean gestational age (GA) at PPROM was 33.50±2.01 weeks of gestation (WG) and the mean rate of PPROM was 25.8% (76/294). GA at FETO was later in the "below umbilicus" group (29.0±1.25 WG vs 29.47±1.29 WG, p=0.002) and the duration of FETO was longer in the "above umbilicus" group (14.49 min [interquartile range-IQR: 8.00-21.00] vs 11.00 min [IQR: 7.00-14.49], p=0.002). After balancing for possible confounding factors, entry point below the umbilicus did not increase the risk of PPROM (adjusted OR: 1.56, 95%CI: [0.89-2.74], p=0.120) and had no effect on the time point at membrane rupture (adjusted HR: 1.56, 95% CI: [0.95-2.55], p=0.080). CONCLUSION: There was no evidence that uterine entry site was correlated with the risk of PPROM before balloon removal. This article is protected by copyright. All rights reserved.

Diseño de un modelo de ronda de seguridad para unidades de cuidados intensivos / Design of a safety round model for intensive care units

Introducción: Las rondas de seguridad (RS) son una herramienta operativa que permite conocer la adherencia a las buenas prácticas, ayuda a identificar riesgos e incidentes en seguridad del paciente (SP), permitiendo implementar acciones de mejora. El objetivo de este trabajo fue el diseño de un procedimiento para realizar RS en una unidad de cuidados intensivos (UCI). Métodos: Elaboración de un listado de verificación para el desarrollo de RS en una UCI mediante técnica de grupo nominal, con la participación de directivos, mandos intermedios y profesionales de diferentes disciplinas y categorías. En primer lugar, un grupo de expertos consensuó, atendiendo a las recomendaciones en buenas prácticas en SP, la definición de ítems, su codificación, los criterios de cumplimiento y el impacto de su incumplimiento. Posteriormente, determinó su viabilidad mediante un estudio transversal a través del pilotaje de 2 RS para ajustar los ítems en condiciones de práctica clínica real. Resultados: Se ha obtenido un modelo de RS específico para UCI mediante un listado de verificación. El grupo de expertos elaboró un primer listado compuesto por 39 ítems de 6 dimensiones esenciales y definió el modo de realización. El tiempo medio de realización de las 2 RS fue de 85minutos, incluyendo el briefing y debriefing posterior. Tras el pilotaje de validación se redujo las dimensiones a 5, se suprimió 3 ítems, se trasladó 2 ítems a otra dimensión y se modificó 3 ítems relativos a infecciones nosocomiales y consentimiento informado. Además, se redefinieron las fuentes de datos, los criterios de cumplimiento y su peso relativo. El listado definitivo fue considerado útil y relevante para mejorar la práctica. Conclusiones: Mediante una metodología de consenso se ha construido un listado de verificación para ser usado en las RS de una UCI. Este modelo puede servir de base para su empleo en servicios asistenciales de similares características.(AU)

Introduction: Safety Rounds (SR) are an operational tool that allow knowing adherence to good practices, help identify risks and incidents in patient safety (PS), allowing improvement actions to be implemented. The objective of this work was the design of a procedure to perform SR in an Intensive Care Unit (ICU). Methods: Preparation of a checklist for the development of SR in the ICU through the nominal group technique, with the participation of managers, middle managers and professionals from different disciplines and categories. In the first place, a group of experts agreed, based on the recommendations on good practices in PS, the definition of items, their coding, the criteria for compliance and the impact of non-compliance. Subsequently, its viability was determined through a cross-sectional study through the piloting of two SRs to adjust the items in real clinical practice conditions. Results: A specific SR model for ICUs has been obtained through a checklist. The group of experts prepared a first list made up of 39 items of 6 essential dimensions and defined the method of implementation. Mean time to complete the two SRs was 85minutes, including the briefing and subsequent debriefing. After the validation pilot, the dimensions were reduced to 5, 3 items were deleted, 2 items were transferred to another dimension and 3 items related to nosocomial infections and informed consent were modified. In addition, the data sources, the compliance criteria and their relative weight were redefined. The final list was considered useful and relevant to improve practice. Conclusions: Through a consensus methodology, a checklist has been built to be used in the RS of an ICU. This model can serve as a basis for its use in healthcare services with similar characteristics.(AU)

Reconstrucción mandibular con cortical autóloga auto trasplantada del sitio quirúrgico en queratoquiste, revisión de literatura y reporte de caso / Mandibular reconstruction with autologous cortical bone transplanted from the surgical site in keratocyst, literature review, and case report

El queratoquiste es un quiste odontogénico en el cual se describen diferentes opciones terapéuticas tanto conservadores como agresivas, con diferentes tasas de éxito y recidivas. Dependiendo del tratamiento, las técnicas más agresivas presentan mejores resultados, pero involucran un mayor defecto óseo en la zona tratada versus las técnicas conservadoras. El propósito de este reporte de caso es documentar una técnica quirúrgica utilizada en un paciente masculino de 17 años que, tras un tratamiento descompresivo de 8 meses, fue sometido a cirugía con enucleación de la lesión remanente más curetaje mecánico perilesional y uso de solución de Carnoy no modificada, preservando la cortical ósea vestibular mandibular tratada con solución de Carnoy no modificada y reposicionando este segmento óseo mediante osteosíntesis. Se realizó seguimiento clínico e imagenológico postoperatorio de 1 año verificando la remisión del quiste y la neoformación ósea en la zona intervenida. El uso de esta alternativa terapéutica permite evitar el colapso de los tejidos blandos en el defecto óseo subyacente y aportar tejido óseo autógeno tratado que permite una funcionalidad de tramado óseo al cual pueden migrar los elementos celulares para aportar en la regeneración tisular local.

The keratocyst is an odontogenic cyst in which different conservative and aggressive therapeutic options are described, with different success rates and recurrences. Depending on the treatment, the most aggressive techniques present better results but involve a more significant bone defect in the treated area compared to conservative techniques. The purpose of this case report is to document a surgical technique used in a 17-year-old male patient who underwent surgery after eight months of decompressive treatment with enucleation of the remaining lesion plus perilesional mechanical curettage and use of Carnoy's solution unmodified, preserving the mandibular vestibular bone cortex treated with unmodified Carnoy's solution and repositioning this bone segment by osteosynthesis. A one-year postoperative clinical and imaging follow-up was carried out, verifying the remission of the cyst and the new bone formation in the operated area. This therapeutic alternative makes possible to avoid the collapse of the soft tissues in the underlying bone defect and provide treated autogenous bone tissue that allows a bone mesh functionality to which the cellular elements can migrate to contribute to local tissue regeneration.

Assessing the Effect of the U.S. Vaccination Program on the Coronavirus Positivity Rate With a Multivariate Framework.

The factors influencing the incidence of COVID-19, including the impact of the vaccination programs, have been studied in the literature. Most studies focus on one or two factors, without considering their interactions, which is not enough to assess a vaccination program in a statistically robust manner. We examine the impact of the U.S. vaccination program on the SARS-CoV-2 positivity rate while simultaneously considering a large number of factors involved in the spread of the virus and the feedbacks among them. We consider the effects of the following sets of factors: socioeconomic factors, public policy factors, environmental factors, and non-observable factors. A time series Error Correction Model (ECM) was used to estimate the impact of the vaccination program at the national level on the positivity rate. Additionally, state-level ECMs with panel data were combined with machine learning techniques to assess the impact of the program and identify relevant factors to build the best-fitting models. We find that the vaccination program reduced the virus positivity rate. However, the program was partially undermined by a feedback loop in which increased vaccination led to increased mobility. Although some external factors reduced the positivity rate, the emergence of new variants increased the positivity rate. The positivity rate was associated with several forces acting simultaneously in opposite directions such as the number of vaccine doses administered and mobility. The existence of complex interactions, between the factors studied, implies that there is a need to combine different public policies to strengthen the impact of the vaccination program.

Design of a safety round model for intensive care units.

INTRODUCTION: Safety Rounds (SR) are an operational tool that allow knowing adherence to good practices, help identify risks and incidents in patient safety (PS), allowing improvement actions to be implemented. The objective of this work was the design of a procedure to perform SR in an Intensive Care Unit (ICU). METHODS: Preparation of a checklist for the development of SR in the ICU through the nominal group technique, with the participation of managers, middle managers and professionals from different disciplines and categories. In the first place, a group of experts agreed, based on the recommendations on good practices in PS, the definition of items, their coding, the criteria for compliance and the impact of non-compliance. Subsequently, its viability was determined through a cross-sectional study through the piloting of two SRs to adjust the items in real clinical practice conditions. RESULTS: A specific SR model for ICUs has been obtained through a checklist. The group of experts prepared a first list made up of 39 items of 6 essential dimensions and defined the method of implementation. Mean time to complete the two SRs was 85 min, including the briefing and subsequent debriefing. After the validation pilot, the dimensions were reduced to 5, 3 items were deleted, 2 items were transferred to another dimension and 3 items related to nosocomial infections and informed consent were modified. In addition, the data sources, the compliance criteria and their relative weight were redefined. The final list was considered useful and relevant to improve practice. CONCLUSIONS: Through a consensus methodology, a checklist has been built to be used in the RS of an ICU. This model can serve as a basis for its use in healthcare services with similar characteristics.

Inference for a discretized stochastic logistic differential equation and its application to biological growth.

In this paper, we present a method to adjust a stochastic logistic differential equation (SLDE) to a set of highly sparse real data. We assume that the SLDE have two unknown parameters to be estimated. We calculate the Maximum Likelihood Estimator (MLE) to estimate the intrinsic growth rate. We prove that the MLE is strongly consistent and asymptotically normal. For estimating the diffusion parameter, the quadratic variation of the data is used. We validate our method with several types of simulated data. For more realistic cases in which we observe discretizations of the solution, we use diffusion bridges and the stochastic expectation-maximization algorithm to estimate the parameters. Furthermore, when we observe only one point for each path for a given number of trajectories we were still able to estimate the parameters of the SLDE. As far as we know, this is the first attempt to fit stochastic differential equations (SDEs) to these types of data. Finally, we apply our method to real data coming from fishery. The proposed adjustment method can be applied to other examples of SDEs and is highly applicable in several areas of science, especially in situations of sparse data.

Immunohistochemistry for FOSB and FOS is a Useful Ancillary Tool in the Diagnosis of Epithelioid Hemangioma but There are Pitfalls in Interpretation Including Expression in Other Vascular Lesions.

Introduction. Epithelioid hemangioma is a benign vascular neoplasm associated with FOS and/or FOSB protein overexpression detected by immunohistochemistry (IHC). Methods. The aim of our study was to determine the co-expression or independent IHC expression of FOS and FOSB in a cohort of epithelioid hemangiomas. We also included two cohorts of other vascular lesions: papillary endothelial hyperplasia and lobular capillary hemangioma / pyogenic granuloma. Results. We identified 50 cases of epithelioid hemangioma, 84% of which were cutaneous and the remaining involved other anatomic locations. Over two thirds of all cases expressed FOSB (68%; 34/50) while FOS immunoreactivity was identified in 46% of all cases. Co-expression of FOSB and FOS occurred in 37% of cases while 76% of all cases stained for at least one of the antibodies. Fifty-eight percent (n = 14/24) and 33% (8/24) of all cases of papillary endothelial hyperplasia expressed FOS and FOSB, respectively. Thirty-two per cent of lobular capillary hemangiomas (n = 8/25) were positive for either FOS or FOSB. Conclusion. In summary, we present the largest cohort of epithelioid hemangiomas assessed with both FOS and FOSB and demonstrated that the use of both antibodies increases the detection rate of these proliferations by 10%. Nonetheless, the use of thresholds may not be appropriate, as only a subset of lesional endothelial cells label with FOS/FOSB. Over half of all cases of papillary endothelial hyperplasia and a third of lobular capillary hemangiomas also displayed immunoreactivity with FOS and/or FOSB.

Association between antimicrobial resistance and biofilm forming ability of Salmonella enterica serotypes from commercial broiler farms in Brazil.

1. This study determined the antimicrobial resistance profile and the biofilm-forming ability of Salmonella enterica strains isolated from commercial broiler houses over a three-year period in southern Brazil.2. Of the 720 drag swabs analysed, 37 (5%) tested positive for non-typhoidal Salmonella spp. and S. Heidelberg was the most frequent serovar.3. Among the antimicrobial resistant strains (83.8%; 31/37), resistance was most common to tetracycline, ampicillin and nalidixic acid. Multidrug resistance was found in 65% (24/37) of the isolates, with a large proportion of multidrug resistant S. Heidelberg strains (81%; 13/16).4. In total, 65% (24/37) of the isolates showed the ability to produce biofilm and multiple antimicrobial resistance was negatively correlated with biofilm formation.5. Strains susceptible to all tested antimicrobials tended to form stronger biofilms than multidrug resistant ones. This suggested that Salmonella spp. with less antimicrobial resistance depend more on the protection provided by biofilm to survive in the farm environment.

Foot and ankle ability measure: validación de la versión española de 29 ítems en el área de rehabilitación / Foot and ankle ability measure: Validation of a Spanish version with 29 items in rehabilitation setting

Objetivo: El Foot and Ankle Ability Measure (FAAM) es un cuestionario extendido internacionalmente para patología de pie y tobillo. El propósito del estudio fue desarrollar y validar la versión española de 29 ítems del cuestionario FAAM para las subescalas de Actividades de la Vida Diaria (AVD) y DEPORTE en el área de rehabilitación. Materiales y métodos: Se realizó un estudio observacional en dos fases. Primero, se hizo una adaptación transcultural del cuestionario FAAM con una traducción doble al español y doble traducción inversa al inglés. Posteriormente, se validaron las propiedades psicométricas. Los participantes (n = 147), con patología de pie y tobillo, completaron la versión española del FAAM para AVD y DEPORTE, el cuestionario SF-36 y la Escala Analógica Visual de Dolor (EVA). La muestra se empleó para determinar la estructura factorial, consistencia interna y validez convergente y, un subgrupo (n = 46), para determinar la fiabilidad a las 48-72 h. Resultados: La estructura factorial de la versión española del FAAM para AVD y DEPORTE fue unidimensional demostrando alta consistencia interna en ambas subescalas (AVD y DEPORTE, α = 0,97 y α = 0,93, respectivamente). Los valores de fiabilidad fueron de ICC = 0,90 y ICC = 0,76, respectivamente. La validez convergente del cuestionario FAAM con la EVA dolor (r = 0,50) y con la función física de la SF-36 (r = 0,64) se correlacionó moderadamente. Conclusiones: La versión española del FAAM de 29 ítems es un instrumento de medida válido para patologías de pie y tobillo con unas propiedades psicométricas similares a la versión original y a las versiones en otros idiomas.(AU)

Objective: The Foot and Ankle Ability Measure (FAAM) is an internationally widely used outcome measure of foot and ankle disorders available in several languages. The purpose of this study was to develop and validate a FAAM Spanish-version with 29 items of Activities of Daily Living (ADL) and SPORT subscales in rehabilitation setting. Materials and methods: A two-stage observational study was conducted. The FAAM was cross-culturally adapted to Spanish through a double-forward translation and a double-backward translation; the psychometric properties were then validated. The participants (n = 147), with various chronic foot and ankle disorders, completed the Spanish version of the Foot and Ankle Ability Measure ADL and SPORT, SF-36, and a pain intensity visual analogue scale (Pain VAS). The full sample was used to determine the factor structure, the internal consistency, and the convergent criterion validity, and a subgroup (n = 46) was used to determine the reliability at 48–72 h. Results: The factor structure of Spanish version of FAAM ADL and SPORT subscales were both one-dimensional, demonstrating high internal consistency (α = 0.97 and α = 0.93, respectively). The reliability values were ICC = 0.90 and ICC = 0.76, respectively. The convergent validity criterion of Spanish version of FAAM with the Pain VAS (r = 0.50) and Physical Function of SF-36 (r = 0.64) were moderately correlated. Conclusions: The Spanish version of FAAM with 29 items are a valid foot and ankle disorder outcome measure with similar psychometric properties to the original version and versions in other languages.(AU)

Comprende el medicamento/descubre al farmacéutico. Resultados preliminares 2021 y 2022 en Canarias. Cursos diana / Understand the medicine/discover the pharmacist. Preliminary results 2021 and 2022 in the Canary Islands. Target courses

INTRODUCCIÓN: en 2021 el proyecto CONÓCEME: comprende el medicamento/descubre al farmacéutico, va dirigido también a estudiantes de 4º o 3º Educación Secundaria Obligatoria (ESO) con el fin de llegar a todos los adolescentes.OBJETIVOS: evaluar la diferencia de aprendizaje de las nociones básicas del uso adecuado del medicamento entre estudiantes de 1º bachillerato, 4º y 3º ESO. Impartir la intervención educativa (IE) como una actividad complementaria en el programa educativo para inculcar buenos hábitos desde la adolescencia con la finalidad de conseguir un uso responsable del medicamento a medio y largo plazo. Evaluar el grado de satisfacción con la actividad de los estudiantes participantes.MATERIAL Y MÉTODOS: estudio observacional descriptivo, transversal, prospectivo, multicéntrico, realizado en las dos provincias canarias durante 2021/2022. Se realizaron formaciones específicas a los farmacéuticos comunitarios (FC) que impartieron las IE informándoles sobre el proyecto y proporcionándoles la documentación asociada, con la finalidad de conseguir intervenciones lo más homogéneas posibles en todas las provincias. La actividad fue impartida por uno o dos FC en dos sesiones. Después de cada IE los estudiantes resolvieron cinco ejercicios en la plataforma del proyecto. Tras los ejercicios rellenaron una encuesta de satisfacción. RESULTADOS: a fecha 11/03/2022, participaron 9 centros educativos, 6 en Santa Cruz de Tenerife y 3 en Las Palmas. Participaron 393 estudiantes, 246 de 1º bach, 75 de 4º ESO y 72 de 3º ESO. Colaboraron 13 FC impartiendo la IE en 19 aulas, 12_1ºbach, 3_4ºESO y 4_3ºESO. (AU)

Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer.

Intratumoral heterogeneity is caused by genomic instability and phenotypic plasticity, but how these features co-evolve remains unclear. SOX10 is a neural crest stem cell (NCSC) specifier and candidate mediator of phenotypic plasticity in cancer. We investigated its relevance in breast cancer by immunophenotyping 21 normal breast and 1860 tumour samples. Nuclear SOX10 was detected in normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In tumours, nuclear SOX10 was almost exclusive to TNBC, and predicted poorer outcome amongst cross-sectional (p = 0.0015, hazard ratio 2.02, n = 224) and metaplastic (p = 0.04, n = 66) cases. To understand SOX10's influence over the transcriptome during the transition from normal to malignant states, we performed a systems-level analysis of co-expression data, de-noising the networks with an eigen-decomposition method. This identified a core module in SOX10's normal mammary epithelial network that becomes rewired to NCSC genes in TNBC. Crucially, this reprogramming was proportional to genome-wide promoter methylation loss, particularly at lineage-specifying CpG-island shores. We propose that the progressive, genome-wide methylation loss in TNBC simulates more primitive epigenome architecture, making cells vulnerable to SOX10-driven reprogramming. This study demonstrates potential utility for SOX10 as a prognostic biomarker in TNBC and provides new insights about developmental phenotypic mimicry-a major contributor to intratumoral heterogeneity.

Angioplasty with a stent retriever to treat vasospasm secondary to subarachnoid hemorrhage due to an aneurysm: a multicenter study of safety and efficacy.

OBJECTIVE: To determine the safety and efficacy of angioplasty with a retrievable stent in treating vasospasm secondary to subarachnoid hemorrhage (SAH) due to an aneurysm. METHODS: We retrospectively analyzed prospectively collected data from consecutive patients undergoing endovascular angioplasty with a retrievable stent to treat vasospasm related to SAH due to an aneurysm in four neurointerventional radiology departments between January 2018 and July 2019. We included patients aged >18 years with vasospasm >50% of the internal carotid artery (ICA), anterior cerebral artery (ACA), and / or middle cerebral artery (MCA) secondary to SAH due to an aneurysm treated with endovascular angioplasty with a retrievable stent. The variables used to measure safety were complications of the procedure and clinical complications. The variables used to measure radiological efficacy were improvement in the degree of stenosis after endovascular treatment and improvement or normalization of cerebral circulation time CTT). RESULTS: We included 16 angioplasty procedures with retrievable stents in 13 patients, in which 33 arterial segments were treated (10 ICA, 15 MCA, and 8 ACA). We observed no complications of the procedure in any patients and no clinical complications in patients who were not intubated. All but one of the patients who had delayed CTT at the beginning of the procedure showed improvements in CTT. The mean improvement in the degree of stenosis was 18% ± 11.65% in the ICA, 30.67% ± 18.45% in the MCA, and 28.38% ± 15.49% in the ACA. No statistically significant associations were observed between endovascular treatment variables and the degree of improvement in stenosis. CONCLUSION: Angioplasty with a retrievable stent is a safe and efficacious treatment for vasospasm secondary to SAH due to an aneurysm, improving CTT and stenosis.

Myeloid sarcoma and extramedullary hematopoiesis expand the spectrum of ERG-positive proliferations: an ancillary tool in the diagnosis.

ERG overexpression has been linked to acute myeloid leukemia/myeloid sarcoma (MS). The aim of our study was to identify the frequency of ERG immunohistochemical (IHC) expression in MS (n = 21), blastic plasmacytoid dendritic cell neoplasms (BPDCNs; n = 8), extramedullary hematopoiesis (EMH: n = 9), normal and pathological bone marrow trephine biopsies (BM-TBs, n = 18), and the marrow component of adrenal myelolipomas (n = 15). ERG-positive and ERG-negative immunostains were identified in 68.4% and 31.5% of patients with MS, respectively (2-3+, 20% to >90% of cells), while all BPDCNs were negative. ERG + MS cases were over-represented in those of myeloid differentiation when compared with those of pure monocytic/monoblastic differentiation, which were ERG-negative (P=<0.001). ERG was expressed in immature myeloid cells in 100% of cases of EMH, BM-TBs, and adrenal myelolipomas (n = 42), resulting in a sensitivity of 100% in this setting. Negative ERG immunostaining was also 100% sensitive in discriminating cells of erythroid lineage, mature lymphocytes, and reactive or neoplastic plasma cells. Variable IHC expression occurred in megakaryocytes and neutrophils. In summary, we confirmed a high frequency of ERG expression in MS and identified ubiquitous expression in non-neoplastic immature myeloid lineage cells. We believe that ERG can be of diagnostic utility to identify neoplastic and reactive myeloid infiltrates in peripheral tissues and possibly as an ancillary marker to exclude the diagnosis of BPDCNs when positive. However, ERG must be used in an antibody panel, as expression is not limited to myeloid cells.

Negative MDM2/CDK4 immunoreactivity does not fully exclude MDM2/CDK4 amplification in a subset of atypical lipomatous tumor/ well differentiated liposarcoma.

Our main goal was to investigate the potential utility of MDM2/CDK4 immunohistochemistry to act as surrogate for FISH to identify a subset of lipoma-like ALT/WDL that might, otherwise, be underdiagnosed on initial screening. Lack of cytologic atypia in lipomatous tumors with negative expression for MDM2/CDK4 IHC does not fully exclude the possibility of underlying MDM2/CDK4 amplification. Present study identified that isolated CDK4/p16 positive expression, in the absence of MDM2 expression, may have potential utility during the initial screening of these tumors but the proportion of conventional lipomas, which may also exhibit low levels of CDK4/p16 expression remains uncertain.