Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT

[EN] Despite the complete treatment with surgery, chemotherapy and radiotherapy, patients with glioblastoma have a devasting prognosis. Although the role of extending temozolomide treatment has been explored, the results are inconclusive. Recent evidence suggested that tumor vascularity may be a modulating factor in combination with methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene on the effect of temozolomide-based therapies, opening new possibilities for personalized treatments. Before proposing a prospective interventional clinical study, it is necessary to confirm the beneficial effect of the combined effect of MGMT methylation and moderate tumor vascularity, as well as the lack of benefit of temozolomide in patients with a highly vascular tumor.In this study, we evaluated the benefit on survival of the combination of methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene and moderate vascularity in glioblastoma using a retrospective dataset of 123 patients from a multicenter cohort. MRI processing and calculation of relative cerebral blood volume (rCBV), used to define moderate- and high-vascular groups, were performed with the automatic ONCOhabitats method. We assessed the previously proposed rCBV threshold (10.7) and the new calculated ones (9.1 and 9.8) to analyze the association with survival for different populations according to vascularity and MGMT methylation status. We found that patients included in the moderate-vascular group had longer survival when MGMT is methylated (significant median survival difference of 174 days, p = 0.0129*). However, we did not find significant differences depending on the MGMT methylation status for the high-vascular group (p = 0.9119). In addition, we investigated the combined correlation of MGMT methylation status and rCBV with the prognostic effect of the number of temozolomide cycles, and only significant results were found for the moderate-vascular group. In conclusion, there is a lack of benefit of extending temozolomide treatment for patients with high vascular glioblastomas, even presenting MGMT methylation. Preliminary results suggest that patients with moderate vascularity and methylated MGMT glioblastomas would benefit more from prolonged adjuvant chemotherapy.M.A-T was supported by DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I+D+i). This work was partially supported by the ALBATROSS project (National Plan for Scientific and Technical Research and Innovation 2017-2020, No. PID2019-104978RB-I00). This study was partially funded by the Fundacio La Marato TV3 (665/C/2013) (http://www.ccma.cat/tv3/marato/projectes-financats/2012/231/ Accessed on 8th September 2021). (JMGG); H2020-SC1-2016-CNECT Project (No. 727560) (JMGG), and H2020-SC1-BHC-2018-2020 (No. 825750) (JMGG). EFG was supported by the European Unions Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844646 and South-Eastern Norway Regional Health Authority Grant 2021057.Álvarez-Torres, MDM.; Fuster García, E.; Balaña, C.; Puig, J.; Garcia-Gomez, JM. (2021). Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT. Cancers. 13(21):1-14. https://doi.org/10.3390/cancers13215420S114132

Uso de escáner láser 3D para el registro del estado previo a la intervención de la Fuente de los Leones de La Alhambra

[ES] En el proceso de restauración y conservación del patrimonio histórico se hace necesaria la utilización de todas las técnicas disponibles que puedan aportar un adecuado conocimiento del proceso que se realice. En este artículo presentamos los trabajos realizados mediante el uso de escáner láser 3D para el registrado y documentación del estado de la Fuente de los Leones de La Alhambra, previos a las intervenciones de restauración que se están realizando. En primer lugar presentamos las técnicas clásicas usadas para el registro gráfico de las actuaciones, describiendo cómo se ha hecho hasta ahora, para después mostrar el nuevo proceso implantado con la utilización del escáner láser, y ver los resultados obtenidos. Para finalizar, describiremos algunas de las aplicaciones en las que se pretende utilizar el registrado obtenido.[EN] In the process of restoration and conservation of cultural heritage it’s necessary to use all available techniques that can contribute to a suitable knowledge of the process. In this paper we present the use of the 3D laser scanner for documenting the state of the Fuente de los Leones of the Alhambra, previous to the interventions of restoration that are being carried out at the moment. First, we present the classic techniques used for the graphical registry of the activities, describing how they have been used until now. Then, we describes the new process implanted with the use of the laser scanner, and show some results obtained. Finally, we describe some of the applications for which we plan to use the obtained models.Patronato de la Alhambra y Generalife, Ministerio de Ciencia y Tecnología y los fondos FEDER, a través del proyecto TIN2007-67474-C03-02, Consejería de innovación Ciencia y Empresa de la Junta de Andalucía a través del proyecto de excelencia TIC-401.Cano, P.; Lamolda Álvarez, F.; Torres, JC.; Villafranca, MDM. (2010). Uso de escáner láser 3D para el registro del estado previo a la intervención de la Fuente de los Leones de La Alhambra. Virtual Archaeology Review. 1(2):89-94. https://doi.org/10.4995/var.2010.4695OJS899412VALLE, J. M. (2006): Reflexiones sobre la Documentación Geométrica del Patrimonio. Papeles del Partal, núm. 3. [http://www.academiadelpartal.org/revista/revista_03/n3_8.pdf ]PAG (2004): Memoria de Intervención en el León nº 4 de la Fuente de los Leones. 2002-2004. Patronato de la Alhambra y Generalife.ALMAGRO, A. (1996): Realización de mapas de daños y de volumen: Fotogrametría. Curso: "Técnicas de diagnostico aplicadas a la conservación de bienes muebles".TIENZA, C. (2007): Proyecto integral de conservación-restauración en la Fuente de los Leones. Palacio y Patio de los Leones de la Alhambra. Informes de seguimiento de la intervención. Documento de trabajo del Servicio de Conservación, Patronato de la Alhambra y Generalife.GONZÁLEZ, A. (2006). Aportaciones de los sistemas de tratamiento digital de imagen en el estudio de las obras de arte. Innovación tecnológica en la Conservación y Restauración del patrimonio. U.A. MadridMINOLTA (2008): Escáner 3D Konica Minolta Vivid 910. [ http://www.minolta3d.com ]TORRES, J.C.; MELERO, F.J.; CANO, P.; MARTÍN, D.; LEÓN, A. (2007): Generación automatizada de modelado 3D para difusión y documentación del patrimonio histórico". En: Hernández, L. y Flores, J. (eds.) "Informática Gráfica y Patrimonio Histórico". pp: 111- 120.ESPAÑA, M.; MORENO, J.J.; MARTIN, D.; CANO, P. (2008): Herramientas para la triangulación y registrado inicial de modelos 3D a partir de nubes de puntos. Congreso Español de Informática Gráfica, pp: 261-264.SCHROEDER, W.J.; ZARGE, J. A.; LORENSEN, W. E. (1992): Decimation of Triangle Meshes. Proceedings of the 19th annual conference on Computer graphics and interactive techniques, pp. 65-70. http://dx.doi.org/10.1145/133994.134010http://dx.doi.org/10.1145/142920.134010HOPPE, H. ; DEROSE, T.; DUCHAMP, T.; MCDONALD, J.; STUELZLE, W. (1993): Mesh Optimization. ACM SIGGRAPH 1993, pp. 19-26. http://dx.doi.org/10.1145/166117.16611

Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification

[EN] Background The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification. Methods Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts' supervision, achieving an accuracy of 88.8% of overlay. Spearman's correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples. Results Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2-2.5 times higher rCBV values in IDH-wildtype glioblastoma samples. Conclusions The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.This work was funded by grants from the National Plan for Scientific and Technical Research and Innovation 2017-2020, No. PID2019-104978RB-I00) (JMGG); H2020-SC1-2016-CNECT Project (No. 727560) (JMGG), and H2020SC1-BHC-2018-2020 (No. 825750) (JMGG). M.A.T was supported by DPI201680054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I + D + i). EFG was supported by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844646. The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.Álvarez-Torres, MDM.; Fuster García, E.; Juan-Albarracín, J.; Reynes, G.; Aparici-Robles, F.; Ferrer Lozano, J.; Garcia-Gomez, JM. (2022). Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification. BMC Cancer. 22(1):1-13. https://doi.org/10.1186/s12885-021-09117-411322

Differential effect of vascularity between long- and short-term survivors with IDH1/2 wild-type glioblastoma

[EN] Introduction: IDH1/2 wt glioblastoma (GB) represents the most lethal tumour of the central nervous system. Tumour vascularity is associated with overall survival (OS), and the clinical relevance of vascular markers, such as rCBV, has already been validated. Nevertheless, molecular and clinical factors may have different influences on the beneficial effect of a favourable vascular signature. Purpose: To evaluate the association between the rCBV and OS of IDH1/2 wt GB patients for long-term survivors (LTSs) and short-term survivors (STSs). Given that initial high rCBV may affect the patient's OS in follow-up stages, we will assess whether a moderate vascularity is beneficial for OS in both groups of patients. Materials and methods: Ninety-nine IDH1/2 wt GB patients were divided into LTSs (OS >= 400 days) and STSs (OS < 400 days). Mann-Whitney and Fisher, uni- and multiparametric Cox, Aalen's additive regression and Kaplan-Meier tests were carried out. Tumour vascularity was represented by the mean rCBV of the high angiogenic tumour (HAT) habitat computed through the haemodynamic tissue signature methodology (available on the ONCOhabitats platform). Results: For LTSs, we found a significant association between a moderate value of rCBV(mean) and higher OS (uni- and multiparametric Cox and Aalen's regression) (p = 0.0140, HR = 1.19; p = 0.0085, HR = 1.22) and significant stratification capability (p = 0.0343). For the STS group, no association between rCBV(mean) and survival was observed. Moreover, no significant differences (p > 0.05) in gender, age, resection status, chemoradiation, or MGMT methylation were observed between LTSs and STSs. Conclusion: We have found different prognostic and stratification effects of the vascular marker for the LTS and STS groups. We propose the use of rCBV(mean) at HAT as a vascular marker clinically relevant for LTSs with IDH1/2 wt GB and maybe as a potential target for randomized clinical trials focused on this group of patients.DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I +D+i).; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 844646; H2020-SC1-BHC-2018-2020 (No. 825750); MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R); European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie, Grant/Award Number: 844646; Research Council of Norway, Grant/Award Number: 261984; South-Eastern Norway Regional Health Authority, Grant/Award Number: 2017073; European Research Council (ERC) under the European Union's Horizon 2020, Grant/Award Number: 758657Álvarez-Torres, MDM.; Fuster García, E.; Reynes, G.; Juan-Albarracín, J.; Chelebian-Kocharyan, EA.; Oleaga, L.; Pineda, J.... (2021). Differential effect of vascularity between long- and short-term survivors with IDH1/2 wild-type glioblastoma. NMR in Biomedicine. 34(4):1-11. https://doi.org/10.1002/nbm.446211134

MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas

[EN] Objectives To assess the combined role of tumor vascularity, estimated from perfusion MRI, andMGMTmethylation status on overall survival (OS) in patients with glioblastoma. Methods A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships betweenMGMTand perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored byMGMTmethylation in terms of OS. Results rCBV distributions did not differ significantly (p > 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV 10.73), however, there was no significant effect ofMGMTmethylation (HR = 1.72,p = 0.10, AUC = 0.56). Conclusions Our results indicate the existence of complementary prognostic information provided byMGMTmethylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most fromMGMTmethylation. Not considering this information may lead to bias in the interpretation of clinical studies.Open Access funding provided by University of Oslo (incl Oslo University Hospital). This study has received funding from MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R) (JMGG); H2020-SC12016-CNECT Project (No. 727560) (JMGG), H2020-SC1-BHC-20182020 (No. 825750) (JMGG), the European Research Council (ERC) under the European Union's Horizon 2020 (Grant Agreement No. 758657), the South-Eastern Norway Regional Health Authority Grants 2017073 and 2013069, the Research Council of Norway Grants 261984 (KEE). M.A.T was supported by Programa Estatal de Promocion del Talento y su Empleabilidad en I+D+i (DPI2016-80054-R). E.F.G was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement (No. 844646).Fuster García, E.; Lorente Estellés, D.; Álvarez-Torres, MDM.; Juan-Albarracín, J.; Chelebian-Kocharyan, EA.; Rovira, A.; Auger Acosta, C.... (2021). MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas. European Radiology. 31(3):1738-1747. https://doi.org/10.1007/s00330-020-07297-41738174731

Temporal series analysis of population cycle threshold counts as a predictor of surge in cases and hospitalizations during the SARS-CoV-2 pandemic

Tools to predict surges in cases and hospitalizations during the COVID-19 pandemic may help guide public health decisions. Low cycle threshold (CT) counts may indicate greater SARS-CoV-2 concentrations in the respiratory tract, and thereby may be used as a surrogate marker of enhanced viral transmission. Several population studies have found an association between the oscillations in the mean CT over time and the evolution of the pandemic. For the first time, we applied temporal series analysis (Granger-type causality) to validate the CT counts as an epidemiological marker of forthcoming pandemic waves using samples and analyzing cases and hospital admissions during the third pandemic wave (October 2020 to May 2021) in Madrid. A total of 22,906 SARS-CoV-2 RT-PCR-positive nasopharyngeal swabs were evaluated; the mean CT value was 27.4 (SD: 2.1) (22.2% below 20 cycles). During this period, 422,110 cases and 36,727 hospital admissions were also recorded. A temporal association was found between the CT counts and the cases of COVID-19 with a lag of 9–10 days (p ≤ 0.01) and hospital admissions by COVID-19 (p < 0.04) with a lag of 2–6 days. According to a validated method to prove associations between variables that change over time, the short-term evolution of average CT counts in the population may forecast the evolution of the COVID-19 pandemic

Robust association between vascular habitats and patient prognosis in glioblastoma: an international retrospective multicenter study

This is the peer reviewed version of the following article: del Mar Álvarez-Torres, M., Juan-Albarracín, J., Fuster-Garcia, E., Bellvís-Bataller, F., Lorente, D., Reynés, G., Font de Mora, J., Aparici-Robles, F., Botella, C., Muñoz-Langa, J., Faubel, R., Asensio-Cuesta, S., García-Ferrando, G.A., Chelebian, E., Auger, C., Pineda, J., Rovira, A., Oleaga, L., Mollà-Olmos, E., Revert, A.J., Tshibanda, L., Crisi, G., Emblem, K.E., Martin, D., Due-Tønnessen, P., Meling, T.R., Filice, S., Sáez, C. and García-Gómez, J.M. (2020), Robust association between vascular habitats and patient prognosis in glioblastoma: An international multicenter study. J Magn Reson Imaging, 51: 1478-1486, which has been published in final form at https://doi.org/10.1002/jmri.26958. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] Background Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE). Purpose To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols. Study Type Multicenter retrospective study. Population In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study. Field Strength/Sequence 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium-based contrast agent-enhanced T-1-weighted MRI, T-2- and FLAIR T-2-weighted, and dynamic susceptibility contrast (DSC) T-2* perfusion. Assessment We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBV(max)) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into "vascular" groups were tested. The variability in the markers between individual centers was also assessed. Statistical Tests Uniparametric Cox regression; Kaplan-Meier test; Mann-Whitney test. Results The rCBV(max) derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into "moderate-" and "high-vascular" groups (P < 0.05). The Mann-Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02-0.685; LAT: P = 0.010-0.769; IPE: P = 0.093-0.939; VPE: P = 0.016-1.000). Data Conclusion The rCBV(max) calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability. Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019.This work was partially supported by: MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R) (to J.M.G.G.); H2020-SC1-2016-CNECT Project (No. 727560) (to J.M.G.G.) and H2020-SC1-BHC-2018-2020 (No. 825750) (to J.M.G.G.); M.A.T was supported by DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I + D + i). The data acquisition and curation of the Oslo University Hospital was supported by: the European Research Council (ERC) under the European Union's Horizon 2020 (Grant Agreement No. 758657), the South-Eastern Norway Regional Health Authority Grants 2017073 and 2013069, and the Research Council of Norway Grants 261984 (to K.E.E.). We gratefully acknowledge the support of NVIDIA Corporation with the donation of the Titan V GPU used for this research. E.F.G. was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 844646. Figure 1 was designed by the Science Artist Elena Poritskaya.Álvarez-Torres, MDM.; Juan-Albarracín, J.; Fuster García, E.; Bellvís-Bataller, F.; Lorente, D.; Reynés, G.; Font De Mora, J.... (2020). Robust association between vascular habitats and patient prognosis in glioblastoma: an international retrospective multicenter study. Journal of Magnetic Resonance Imaging. 51(5):1478-1486. https://doi.org/10.1002/jmri.2695814781486515Louis, D. N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W. K., … Ellison, D. W. (2016). The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathologica, 131(6), 803-820. doi:10.1007/s00401-016-1545-1Gately, L., McLachlan, S., Dowling, A., & Philip, J. (2017). 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M., Gutman, D., Scarpace, L., Hwang, S. N., Holder, C. A., … Flanders, A. (2014). Outcome Prediction in Patients with Glioblastoma by Using Imaging, Clinical, and Genomic Biomarkers: Focus on the Nonenhancing Component of the Tumor. Radiology, 272(2), 484-493. doi:10.1148/radiol.14131691Jensen, R. L., Mumert, M. L., Gillespie, D. L., Kinney, A. Y., Schabel, M. C., & Salzman, K. L. (2013). Preoperative dynamic contrast-enhanced MRI correlates with molecular markers of hypoxia and vascularity in specific areas of intratumoral microenvironment and is predictive of patient outcome. Neuro-Oncology, 16(2), 280-291. doi:10.1093/neuonc/not148Jena, A., Taneja, S., Gambhir, A., Mishra, A. K., D’souza, M. M., Verma, S. M., … Sogani, S. K. (2016). Glioma Recurrence Versus Radiation Necrosis. Clinical Nuclear Medicine, 41(5), e228-e236. doi:10.1097/rlu.0000000000001152Price, S. J., Young, A. M. H., Scotton, W. J., Ching, J., Mohsen, L. A., Boonzaier, N. R., … Larkin, T. J. (2015). Multimodal MRI can identify perfusion and metabolic changes in the invasive margin of glioblastomas. Journal of Magnetic Resonance Imaging, 43(2), 487-494. doi:10.1002/jmri.24996Chang, Y.-C. C., Ackerstaff, E., Tschudi, Y., Jimenez, B., Foltz, W., Fisher, C., … Stoyanova, R. (2017). Delineation of Tumor Habitats based on Dynamic Contrast Enhanced MRI. Scientific Reports, 7(1). doi:10.1038/s41598-017-09932-5Cui, Y., Tha, K. K., Terasaka, S., Yamaguchi, S., Wang, J., Kudo, K., … Li, R. (2016). Prognostic Imaging Biomarkers in Glioblastoma: Development and Independent Validation on the Basis of Multiregion and Quantitative Analysis of MR Images. Radiology, 278(2), 546-553. doi:10.1148/radiol.2015150358Juan-Albarracín, J., Fuster-Garcia, E., Pérez-Girbés, A., Aparici-Robles, F., Alberich-Bayarri, Á., Revert-Ventura, A., … García-Gómez, J. M. (2018). Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival. Radiology, 287(3), 944-954. doi:10.1148/radiol.2017170845Fuster-Garcia, E., Juan-Albarracín, J., García-Ferrando, G. A., Martí-Bonmatí, L., Aparici-Robles, F., & García-Gómez, J. M. (2018). Improving the estimation of prognosis for glioblastoma patients by MR based hemodynamic tissue signatures. NMR in Biomedicine, 31(12), e4006. doi:10.1002/nbm.4006Abramson, R. G., Burton, K. R., Yu, J.-P. J., Scalzetti, E. M., Yankeelov, T. E., Rosenkrantz, A. B., … Subramaniam, R. M. (2015). Methods and Challenges in Quantitative Imaging Biomarker Development. Academic Radiology, 22(1), 25-32. doi:10.1016/j.acra.2014.09.001Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., … Mirimanoff, R. O. (2005). Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. 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Differentiation between vasogenic-edema versus tumor-infiltrative area in patients with glioblastoma during bevacizumab therapy: A longitudinal MRI study. European Journal of Radiology, 83(7), 1250-1256. doi:10.1016/j.ejrad.2014.03.02

Plan de emerxencias. Fundación Pública Urxencias Sanitarias de Galicia-061

A Fundación Pública Urxencias Sanitarias de Galicia-061 é a encargada de proporcionar, desde o momento que ocorre a emerxencia, un control da situación, unha primeira avaliación e unha asistencia sanitaria que logre salvar o maior número de vidas e volver á normalidade o antes posible. Para isto, a actuación sanitaria debe seguir unha metodoloxía perfectamente establecida, xa que as actuacións organizadas son as mellores ferramentas de traballo. Así pois, é necesario posibilitar normas de actuación o máis protocolizadas posible, para poder traballar nas mellores condicións de seguridade e manter unhas directrices xerais, onde cada persoa coñeza tanto a súa función como a do resto dos componentes do equipo, procedendo, ademais, á súa identificación funcional mediante signos externos (uniformidade, carteis, identificación, etc.); para facilitar o entendemento e a coordinación de todos os implicados en resolver a situación acaecida. Con este fin, preséntase o Plan de emerxencias que a continuación se expón, nun afán de dar sempre a mellor e máis axeitada resposta; obxectivo primordial desde que a FPUS de Galicia–061 se instaura como responsable da medicina prehospitalaria na nosa comunidade autónoma.La Fundación Pública Urxencias Sanitarias de Galicia-061 es la encargada de proporcionar, desde el momento en que ocurre la emergencia, un control de la situación, una primera evaluación y una asistencia sanitaria que logre salvar el mayor número de vidas y volver a la normalidad lo antes posible. Para esto, la actuación sanitaria debe seguir una metodología perfectamente establecida, ya que las actuaciones organizadas son las mejores herramientas de trabajo. Así pues, es necesario posibilitar normas de actuación lo más protocolizadas posible, para poder trabajar en las mejores condiciones de seguridad y mantener unas directrices generales, donde cada persona conozca tanto su función como la del resto de los componentes del equipo, procediendo, además, a su identificación funcional mediante signos externos (uniformidad, carteles, identificación, etc.); para facilitar el entendimiento y la coordinación de todos los implicados en resolver la situación acaecidad. Con este fin, se presenta el Plan de emergencias que a continuación se expone, en un afán de dar siempre la respuesta mejor y más idónea; objetivo primordial desde que la FPUS de Galicia-061 se instaura como responsable de la medicina prehospitalaria en nuestra comunidad autónoma

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Variables psicológicas implicadas en la actitud e iniciativa emprendedora (II): personalidad, cognición y emoción

El proyecto titulado: Variables implicadas en la actitud e iniciativa emprendedora (II): personalidad, cognición y emoción, es la continuidad de otro presentado en la convocatoria anterior (2016-2017) cuyo objetivo era evaluar variables psicológicas en la actitud emprendedora de los estudiantes universitarios de la Universidad Complutense de Madrid (UCM). Este segundo proyecto ha tenido por objetivo principal ampliar la evaluación a otras facultades y áreas de conocimiento de nuestra universidad a fin de obtener el mapa y perfil de la iniciativa emprendedora del universitario UCM