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Introducción: “Radiología plus” es una aplicación para dispositivo móvil (app) dirigida a alumnos de Grado de Medicina y de Fisioterapia de la Universidad de Córdoba. La app ha pretendido mostrar a los alumnos de una manera dinámica y ágil las diferentes técnicas de diagnóstico por la imagen, su utilidad para cada patología y área anatómica, y relacionar la imagen con otros datos clínicos. Objetivo: Analizar el uso de la aplicación por parte de los estudiantes. Material y Método: Se recopilaron casos clínicos procedentes del Hospital Universitario Reina Sofía representativos del trabajo diario de un Servicio de Radiología con técnicas clásicas y otras más avanzadas. La plataforma ha permitido a los profesores de la asignatura monitorizar durante el curso el uso de la aplicación por parte de los alumnos. Resultados: El 82% (345 alumnos) del total de estudiantes matriculados hicieron uso de la aplicación. El grado de utilización, en función del número de casos resueltos por cada estudiante ha sido: 37,4% Leve (1-24 casos), 14,4% Moderado (25-49 casos), 24,3% Importante (50-74 casos), 3,8% Muy Importante (75-100 casos) y 2% Excelente (>100 casos). Conclusión: La app ha tenido una amplia acogida por parte de los alumnos a la que estaba dirigida. Introduction: “Radiología plus” is an application for mobile devices (app) for Medicine and Physiotherapy degree students at the University of Córdoba. The app tried to show students in a dynamic and easy way the different diagnostic imaging techniques, their usefulness for each pathology and anatomical area, and relate the image with other clinical data. Objective: To analyze the use of the application by students. Material and Method: Clinical cases from the Reina Sofía University Hospital were collected. They were representative of the daily work of a Radiology Service with classic techniques and other very advanced and innovative techniques of a high technical level. The platform allowed teachers of this subject to monitor the use of it by the students during the course. Results: 82% (345 students) of the total number of students enrolled used the application. The follow-up divided into groups according to the cases resolved by each student was 37,4% Mild (1-24 cases), 14,4% Moderate (25-49 cases), 24,3% Important (50-74 cases), 3,8% Very Important (75-100 cases) y 2% Excellent (>100 cases). Conclusion: The app has been widely received by the students to whom it was addressed.

Objectives To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. Methods The MIPA observational study enrolled women aged 18–80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. Results A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p p = 0.957) for D-MRI, and 1.9 (p Conclusions Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. Key Points • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups.

Background Traumatic brain injury (TBI) is characterized by a primary mechanical injury and a secondary injury associated with neuroinflammation, blood–brain barrier (BBB) disruption and neurodegeneration. We have developed a novel cannabidiol aminoquinone derivative, VCE-004.8, which is a dual PPARγ/CB2 agonist that also activates the hypoxia inducible factor (HIF) pathway. VCE-004.8 shows potent antifibrotic, anti-inflammatory and neuroprotective activities and it is now in Phase II clinical trials for systemic sclerosis and multiple sclerosis. Herein, we investigated the mechanism of action of VCE-004.8 in the HIF pathway and explored its efficacy in a preclinical model of TBI. Methods Using a phosphoproteomic approach, we investigated the effects of VCE-004.8 on prolyl hydroxylase domain-containing protein 2 (PHD2) posttranslational modifications. The potential role of PP2A/B55α in HIF activation was analyzed using siRNA for B55α. To evaluate the angiogenic response to the treatment with VCE-004.8 we performed a Matrigel plug in vivo assay. Transendothelial electrical resistance (TEER) as well as vascular cell adhesion molecule 1 (VCAM), and zonula occludens 1 (ZO-1) tight junction protein expression were studied in brain microvascular endothelial cells. The efficacy of VCE-004.8 in vivo was evaluated in a controlled cortical impact (CCI) murine model of TBI. Results Herein we provide evidence that VCE-004.8 inhibits PHD2 Ser125 phosphorylation and activates HIF through a PP2A/B55α pathway. VCE-004.8 induces angiogenesis in vivo increasing the formation of functional vessel (CD31/α-SMA) and prevents in vitro blood–brain barrier (BBB) disruption ameliorating the loss of ZO-1 expression under proinflammatory conditions. In CCI model VCE-004.8 treatment ameliorates early motor deficits after TBI and attenuates cerebral edema preserving BBB integrity. Histopathological analysis revealed that VCE-004.8 treatment induces neovascularization in pericontusional area and prevented immune cell infiltration to the brain parenchyma. In addition, VCE-004.8 attenuates neuroinflammation and reduces neuronal death and apoptosis in the damaged area. Conclusions This study provides new insight about the mechanism of action of VCE-004.8 regulating the PP2A/B55α/PHD2/HIF pathway. Furthermore, we show the potential efficacy for TBI treatment by preventing BBB disruption, enhancing angiogenesis, and ameliorating neuroinflammation and neurodegeneration after brain injury.

Background Use of artificial intelligence (AI) as a stand-alone reader for digital mammography (DM) or digital breast tomosynthesis (DBT) breast screening could ease radiologists' workload while maintaining quality. Purpose To retrospectively evaluate the stand-alone performance of an AI system as an independent reader of DM and DBT screening examinations. Materials and Methods Consecutive screening-paired and independently read DM and DBT images acquired between January 2015 and December 2016 were retrospectively collected from the Tomosynthesis Cordoba Screening Trial. An AI system computed a cancer risk score (range, 1-100) for DM and DBT examinations independently. AI stand-alone performance was measured using the area under the receiver operating characteristic curve (AUC) and sensitivity and recall rate at different operating points selected to have noninferior sensitivity compared with the human readings (noninferiority margin, 5%). The recall rate of AI and the human readings were compared using a McNemar test. Results A total of 15 999 DM and DBT examinations (113 breast cancers, including 98 screen-detected and 15 interval cancers) from 15 998 women (mean age, 58 years ± 6 [standard deviation]) were evaluated. AI achieved an AUC of 0.93 (95% CI: 0.89, 0.96) for DM and 0.94 (95% CI: 0.91, 0.97) for DBT. For DM, AI achieved noninferior sensitivity as a single (58.4%; 66 of 113; 95% CI: 49.2, 67.1) or double (67.3%; 76 of 113; 95% CI: 58.2, 75.2) reader, with a reduction in recall rate (

Background The workflow of breast cancer screening programs could be improved given the high workload and the high number of false-positive and false-negative assessments. Purpose To evaluate if using an artificial intelligence (AI) system could reduce workload without reducing cancer detection in breast cancer screening with digital mammography (DM) or digital breast tomosynthesis (DBT). Materials and Methods Consecutive screening-paired and independently read DM and DBT images acquired from January 2015 to December 2016 were retrospectively collected from the Córdoba Tomosynthesis Screening Trial. The original reading settings were single or double reading of DM or DBT images. An AI system computed a cancer risk score for DM and DBT examinations independently. Each original setting was compared with a simulated autonomous AI triaging strategy (the least suspicious examinations for AI are not human-read; the rest are read in the same setting as the original, and examinations not recalled by radiologists but graded as very suspicious by AI are recalled) in terms of workload, sensitivity, and recall rate. The McNemar test with Bonferroni correction was used for statistical analysis. Results A total of 15 987 DM and DBT examinations (which included 98 screening-detected and 15 interval cancers) from 15 986 women (mean age ± standard deviation, 58 years ± 6) were evaluated. In comparison with double reading of DBT images (568 hours needed, 92 of 113 cancers detected, 706 recalls in 15 987 examinations), AI with DBT would result in 72.5% less workload (P

// Raul M. Luque 1, 2, 3, 4, 5, *, # , Laura M. Lopez-Sanchez 1, 2, 3, 4, 5, * , Alicia Villa-Osaba 1, 2, 3, 4, 5, * , Isabel M. Luque 1, 3 , Ana L. Santos-Romero 1, 4, 6 , Elena M. Yubero-Serrano 1, 4, 7 , Maria Cara-Garcia 1, 4, 6 , Marina Alvarez-Benito 1, 4, 6 , Jose Lopez-Miranda 1, 4, 7 , Manuel D. Gahete 1, 2, 3, 4, 5, # and Justo P. Castano 1, 2, 3, 4, 5, # 1 Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain 2 Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain 3 Hospital Universitario Reina Sofia, Cordoba, Spain 4 CIBERobn, Cordoba, Spain 5 ceiA3, Cordoba, Spain 6 Mammary Gland Unit, Hospital Universitario Reina Sofia, Cordoba, Spain 7 Lipids and Atherosclerosis Unit, Hospital Universitario Reina Sofia, Cordoba, Spain * These authors contributed equally to this work # These authors co-directed the work and should be considered co-senior authors Correspondence to: Raul M. Luque, email: raul.luque@uco.es Manuel D. Gahete, email: bc2gaorm@uco.es Justo P. Castano, email: justo@uco.es Keywords: breast cancer, glucose, insulin, OGTT, obesity Received: June 27, 2017 Accepted: July 25, 2017 Published: August 23, 2017 ABSTRACT The association between breast cancer (BCa) presence and altered glucose/insulin metabolism is controversial likely due to an inaccurate insulin resistance (IR) assessment and inappropriate stratification of patients by body-mass index (BMI) and menopausal state. 148 women with suspect of sporadic BCa were stratified by BMI and menopause. Fasting levels of glucose, insulin, glycohemoglobin and selected IR-related and tumor-derived markers were measured. Glucose/insulin levels during OGTT were used to calculate insulin resistance/sensitivity indexes. Analysis of 77 BCa-bearing patients and 71 controls showed an association between BCa and IR as demonstrated by impaired glucose/insulin homeostasis (increased fasting- and OGTT-induced glucose levels) and deteriorated IR indexes, which was especially patent in premenopausal women. The association between BCa presence and IR was markedly influenced by BMI, being obese BCa patients significantly more insulin resistant than controls. BCa presence was associated to elevated levels of IR (glucose, triglycerides) and tumor-derived (VEGF) markers, especially in overweight/obese patients. BCa presence is associated to IR in overweight/obese premenopausal but not in premenopausal normal weight or postmenopausal women. Our data support a bidirectional relationship between dysregulated/imbalanced glucose/insulin metabolism and BCa, as tumor- and IR-markers are correlated with the impairment of glucose/insulin metabolism in overweight/obese premenopausal BCa patients.

This study evaluated the use of TachoSil as an adjunctive therapy for reducing axillary lymphocele formation.Eighty-six patients diagnosed with breast cancer N+ and treated with axillary lymphadenectomy received a TachoSil patch in the axillary wound. Using a database of patients without placing a hemostatic patch, we applied a matched case-control in a 1-to-2 fashion. Multiple and logistic regression analyses were used to evaluate postoperative results.Patient group with TachoSil showed a significantly lower drainage volume (P.001) and the length of stay was significantly shorter (P.001). The number of patients with evacuative punctures was 24.5% in the group with patch versus 51.2% in the control group (P.001). In multivariate analysis, the use of TachoSil was a significant predictor of reducing axillary drainage volume (P .001), mean length of hospital stay (P = .001), and number of evacuative punctures of lymphocele (odds ratio .264, 95% confidence interval .144 to .484, P.001).The use of TachoSil in axillary lymphadenectomy may be a safe and useful treatment option for reducing axillary drainage volume, incidence of symptomatic lymphocele, and hospital stay.

Introduction The objective of our study was to assess recurrence after negative sentinel lymph node biopsy (SLNB) and to determine the risk factors related to local and distant recurrence in this group of patients. Materials and Methods We conducted a prospective observational study from 2006 to 2011. It included 607 patients with early-stage breast cancer and negative SLNB with a 5-year follow-up period. Results The disease-free survival rate was 98.5% and 96.5% at 2 and 5 years, respectively. Multivariate analysis identified the following prognostic factors for disease recurrence: tumor necrosis (hazard ratio [HR], 4.89; 95% confidence interval [CI], 1.61-14.89; P = .005), lymphovascular invasion (HR, 3.46; 95% CI, 1.14-10.55; P = .029), T2 tumor size (HR, 4.35; 95% CI, 1.40-13.52; P = .011), and moderate to severe lymphoplasmacytic stromal infiltration (HR, 3.06; 95% CI, 1.18-7.96; P = .022). Conclusion Recurrence in patients with negative SLNB was satisfactorily low. Nevertheless, determining the prognostic factors related to a greater recurrence rate could help identify high-risk patients and influence systemic adjuvant therapy.

Vascular calcification (VC) is a frequent complication of chronic kidney disease (CKD) and is a predictor of cardiovascular morbidity and mortality. In the present study, we investigated the potential involvement of endothelial microparticles (MPs) and endothelial progenitor cells (EPCs) in the generation of VC in CKD patients. The number of circulating EMPs is greater in patients with VC than without VC (307 ± 167 vs. 99 ± 75 EMPs/μl, P < 0.001). The percentage of EPCs is significantly lower in patient with VC than in patients without VC (0.14 ± 0.11% vs. 0.25 ± 0.18%, P = 0.002). The number of EPCs expressing osteocalcin (OCN) was higher in VC patients (349 ± 63 cells/100,000) than in non-VC patients (139 ± 75 cells/100,000, P < 0.01). In vitro, MPs obtained from CKD patients were able to induce OCN expression in EPCs from healthy donors; the increase in OCN expression was more accentuated if MPs were obtained from CKD patients with VC. MPs from CKD patients also induced OCN expression in vascular smooth muscle cells and fibroblasts. In CKD patients, the rise in endothelial MPs associated with a decrease in the number of EPCs, suggesting an imbalance in the processes of endothelial damage and repair in CKD patients, mainly those with VC. Our results suggest that EPCs, through OCN expression, may directly participate in the process of VC.

Background Somatostatin (SST) and cortistatin (CORT), two structurally and functionally related peptides, share a family of widespread receptors (sst1-5) to exert apparently similar biological actions, including endocrine/metabolic regulation and suppression of tumor cell proliferation. However, despite their therapeutic potential, attempts to apply SST-analogs to treat breast cancer have yielded unsatisfactory results. Actually, the specific roles of SST and CORT in mammary gland tumorigenesis (MGT), particularly in relation to metabolic dysregulation (i.e. obesity), remain unknown. Methods The role of endogenous SST and CORT in carcinogen-induced MGT was investigated under normal (lean) and obesity conditions. To that end, SST- and CORT-knockout (KO) mice and their respective littermate-controls, fed low-fat (LF) or high-fat (HF) diets, were treated with 7,12-dimethyl-benza-anthracene (DMBA) once a week (wk) for 3 wk, and MGT was monitored for 25 wk. Additionally, we examined the effect of SST or CORT removal in the development of the mammary gland. Results Lack of SST did not alter DMBA-induced MGT incidence under lean conditions; conversely, lack of endogenous CORT severely aggravated DMBA-induced MGT in LF-fed mice. These differences were not attributable to altered mammary gland development. HF-diet modestly increased the sensitivity to DMBA-induced carcinogenesis in control mice, whereas, as observed in LF-fed CORT-KO, HF-fed CORT-KO mice exhibited aggravated tumor incidence, discarding a major influence of obesity on these CORT actions. In marked contrast, HF-fed SST-KO mice exhibited much higher tumor incidence than LF-fed SST-KO mice, which could be associated with higher mammary complexity. Conclusions Endogenous SST and CORT distinctly impact on DMBA-induced MGT, in a manner that is strongly dependent on the metabolic/endocrine milieu (lean vs. obese status). Importantly, CORT, rather than SST, could represent a major inhibitor of MGT under normal/lean-conditions, whereas both neuropeptides would similarly influence MGT under obesity conditions. The mechanisms mediating these different effects likely involve mammary development and hormones, but the precise underlying factors are still to be fully elucidated. However, our findings comprise suggestive evidence that CORT-like molecules, rather than classic SST-analogs, may help to identify novel tools for the medical treatment of breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0689-1) contains supplementary material, which is available to authorized users.