Global heterogeneity assessed with 18F-FDG PET/CT. Relation with biological variables and prognosis in locally advanced breast cancer. / Medidas de heterogeneidad global y esfericidad con 18F-FDG PET/TC en el cáncer de mama: relación con la biología tumoral, valor predictivo y pronóstico.

AIM: To analyze the relationship between measurements of global heterogeneity, obtained from 18F-FDG PET/CT, with biological variables, and their predictive and prognostic role in patients with locally advanced breast cancer (LABC). MATERIAL AND METHODS: 68 patients from a multicenter and prospective study, with LABC and a baseline 18F-FDG PET/CT were included. Immunohistochemical profile [estrogen receptors (ER) and progesterone receptors (PR), expression of the HER-2 oncogene, Ki-67 proliferation index and tumor histological grade], response to neoadjuvant chemotherapy (NC), overall survival (OS) and disease-free survival (DFS) were obtained as clinical variables. Three-dimensional segmentation of the lesions, providing SUV, volumetric [metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] and global heterogeneity variables [coefficient of variation (COV) and SUVmean/SUVmax ratio], as well as sphericity was performed. The correlation between the results obtained with the immunohistochemical profile, the response to NC and survival was also analyzed. RESULTS: Of the patients included, 62 received NC. Only 18 responded. 13 patients relapsed and 11 died during follow-up. ER negative tumors had a lower COV (p=0.018) as well as those with high Ki-67 (p=0.001) and high risk phenotype (p=0.033) compared to the rest. No PET variable showed association with the response to NC nor OS. There was an inverse relationship between sphericity with DFS (p=0.041), so, for every tenth that sphericity increases, the risk of recurrence decreases by 37%. CONCLUSIONS: Breast tumors in our LABC dataset behaved as homogeneous and spherical lesions. Larger volumes were associated with a lower sphericity. Global heterogeneity variables and sphericity do not seem to have a predictive role in response to NC nor in OS. More spherical tumors with less variation in gray intensity between voxels showed a lower risk of recurrence.

Morphologic Features on MR Imaging Classify Multifocal Glioblastomas in Different Prognostic Groups.

BACKGROUND AND PURPOSE: Multifocal glioblastomas (ie, glioblastomas with multiple foci, unconnected in postcontrast pretreatment T1-weighted images) represent a challenge in clinical practice due to their poor prognosis. We wished to obtain imaging biomarkers with prognostic value that have not been found previously. MATERIALS AND METHODS: A retrospective review of 1155 patients with glioblastomas from 10 local institutions during 2006-2017 provided 97 patients satisfying the inclusion criteria of the study and classified as having multifocal glioblastomas. Tumors were segmented and morphologic features were computed using different methodologies: 1) measured on the largest focus, 2) aggregating the different foci as a whole, and 3) recording the extreme value obtained for each focus. Kaplan-Meier, Cox proportional hazards, correlations, and Harrell concordance indices (c-indices) were used for the statistical analysis. RESULTS: Age (P < .001, hazard ratio = 2.11, c-index = 0.705), surgery (P < .001, hazard ratio = 2.04, c-index = 0.712), contrast-enhancing rim width (P < .001, hazard ratio = 2.15, c-index = 0.704), and surface regularity (P = .021, hazard ratio = 1.66, c-index = 0.639) measured on the largest focus were significant independent predictors of survival. Maximum contrast-enhancing rim width (P = .002, hazard ratio = 2.05, c-index = 0.668) and minimal surface regularity (P = .036, hazard ratio = 1.64, c-index = 0.600) were also significant. A multivariate model using age, surgery, and contrast-enhancing rim width measured on the largest foci classified multifocal glioblastomas into groups with different outcomes (P < .001, hazard ratio = 3.00, c-index = 0.853, median survival difference = 10.55 months). Moreover, quartiles with the highest and lowest individual prognostic scores based on the focus with the largest volume and surgery were identified as extreme groups in terms of survival (P < .001, hazard ratio = 18.67, c-index = 0.967). CONCLUSIONS: A prognostic model incorporating imaging findings on pretreatment postcontrast T1-weighted MRI classified patients with glioblastoma into different prognostic groups.

Labile haemoglobin as a glycaemic biomarker for patient-specific monitoring of diabetes: mathematical modelling approach.

Diabetes mellitus constitutes a major health problem and its clinical presentation and progression may vary considerably. A number of standardized diagnostic and monitoring tests are currently used for diabetes. They are based on measuring either plasma glucose, glycated haemoglobin or both. Their main goal is to assess the average blood glucose concentration. There are several sources of interference that can lead to discordances between measured plasma glucose and glycated haemoglobin levels. These include haemoglobinopathies, conditions associated with increased red blood cell turnover or the administration of some therapies, to name a few. Therefore, there is a need to provide new diagnostic tools for diabetes that employ clinically accessible biomarkers which, at the same time, can offer additional information allowing us to detect possible conflicting cases and to yield more reliable evaluations of the average blood glucose level concentration. We put forward a biomathematical model to describe the kinetics of two patient-specific glycaemic biomarkers to track the emergence and evolution of diabetes: glycated haemoglobin and its labile fraction. Our method incorporates erythrocyte age distribution and utilizes a large cohort of clinical data from blood tests to support its usefulness for diabetes monitoring.

A three-dimensional computational analysis of magnetic resonance images characterizes the biological aggressiveness in malignant brain tumours.

Glioblastoma (GBM) is the most frequent and aggressive type of primary brain tumour. The development of image-based biomarkers from magnetic resonance images (MRIs) has been a topic of recent interest. GBMs on pre-treatment post-contrast T1-weighted (w) MRIs often appear as rim-shaped regions. In this research, we wanted to define rim-shape complexity (RSC) descriptors and study their value as indicators of the tumour's biological aggressiveness. We constructed a set of widths characterizing the rim-shaped contrast-enhancing areas in T1w MRIs, defined measures of the RSC and computed them for 311 GBM patients. Survival analysis, correlations and sensitivity studies were performed to assess the prognostic value of the measurements. All measures obtained from the histograms were found to depend on the class width to some extent. Several measures (FWHM and ßR) had high prognostic value. Some histogram-independent measures were predictors of survival: maximum rim width, mean rim width and spherically averaged rim width. The later quantity allowed patients to be classified into subgroups with different rates of survival (mean difference 6.28 months, p = 0.006). In conclusion, some of the morphological quantifiers obtained from pre-treatment T1w MRIs provided information on the biological aggressiveness of GBMs. The results can be used to define prognostic measurements of clinical applicability.

A mathematical model of low grade gliomas treated with temozolomide and its therapeutical implications.

Low grade gliomas (LGGs) are infiltrative and incurable primary brain tumours with typically slow evolution. These tumours usually occur in young and otherwise healthy patients, bringing controversies in treatment planning since aggressive treatment may lead to undesirable side effects. Thus, for management decisions it would be valuable to obtain early estimates of LGG growth potential. Here we propose a simple mathematical model of LGG growth and its response to chemotherapy which allows the growth of LGGs to be described in real patients. The model predicts, and our clinical data confirms, that the speed of response to chemotherapy is related to tumour aggressiveness. Moreover, we provide a formula for the time to radiological progression, which can be possibly used as a measure of tumour aggressiveness. Finally, we suggest that the response to a few chemotherapy cycles upon diagnosis might be used to predict tumour growth and to guide therapeutical actions on the basis of the findings.

Encuesta de la SEFAP sobre la Farmacia de Atención Primaria y la Ley 29/2006 de garantías y uso racional del medicamento y productos sanitarios / No disponible

Transcurrido un año desde la publicación de la «Ley 29/2006 de garantías y uso racional de los medicamentos yproductos sanitarios», la Sociedad Española de Farmacéuticos de Atención Primaria (SEFAP) quiere conocer lasituación de los servicios de farmacia de atención primaria (SFAP) en el territorio nacional. Material y método.Estudio descriptivo transversal llevado a cabo mediante una encuesta con 128 ítems. Se distribuyó mediante envíoelectrónico desde la web de la SEFAP a todos los socios, especificando que se cumplimentara una encuesta por SFAP.Resultados. Se recibieron un total de 84 encuestas, desestimándose 5 por repetición del mismo SFAP o por no trabajaren un SFAP, lo que representa el 58,1% de los posibles SFAP. El 52% de las estructuras de gestión de atenciónprimaria encuestadas disponen de SFAP autorizados según la normativa vigente y el 59% son los responsables de lagestión de medicamentos. El 99% tienen establecidos sistemas de información sobre gestión de la farmacoterapia(aspectos clínicos, de efectividad, seguridad y eficiencia de la utilización de los medicamentos) y proporcionan unacorrecta información y formación sobre medicamentos y productos sanitarios a los profesionales. El 40% de los SFAPparticipa en la elaboración de criterios de selección de medicamentos para el desarrollo de protocolos y guías farmacoterapéuticasque garanticen la correcta asistencia a los pacientes, y el 27% asesora sobre el historial farmacoterapéuticode los pacientes. El 46% de las estructuras de atención primaria participa en investigación clínica en farmacoterapiade calidad, y el 42% de los SFAP participan en comités éticos y de investigación. El 99% participan confarmacovigilancia y con programas que potencian el uso seguro de los medicamentos. El 41% de los SFAP impulsanprogramas de educación a la población sobre medicamento. Y casi la mitad, el 45% de los SFAP, están participandoya en los planes estratégicos de calidad en las estructuras de gestión de atención primaria. Discusión. Los serviciosde salud deben impulsar y velar por el desarrollo de los SFAP, no sólo regularizando la situación administrativa deéstos conforme a la Ley, sino también promoviendo el desarrollo de las funciones establecidas, favoreciendo la integracióndel farmacéutico de atención primaria en todos los procesos de la cadena terapéutica, y retornando al sistemala corresponsabilidad en la calidad asistencial y la farmacoterapéutica de los pacientes

One year after the publication of Law 29/2006 on the guarantees and rational use of medicines and healthcareproducts the Spanish Society of Primary Care Pharmacists (SEFAP) wishes to know the situation of the PrimaryCare Pharmacy Services (SFAP) in Spain. Material and method: a cross-sectional descriptive study carried outby means of a survey with 128 items. It was distributed to all the members via e-mail from the SEFAP’s web,specifying that one survey should be filled out per Primary Care Pharmacy Service. Results: a total of 84 surveyswere received, 5 of which were rejected because of repetitions of the same SFAP or for not working in a SFAP,representing 58.1% of all possible SFAPs. Of the primary care management structures polled, 52% have SFAPsauthorised according to current legislation and 59% are responsible for the management of medicines. Of the total,99% have established information systems on pharmacotherapy management (clinical aspects, aspects regardingefficacy, safety and the efficiency of the use of the medicines) and provide correct information and training onmedicines and healthcare products to healthcare professionals. Of the SFAPs, 40% participate in the definition ofmedicine selection criteria for the development of protocols and pharmacotherapeutic guides that guarantee thecorrect pharmacotherapeutic care of patients, and 27% provide advice on the patients’ pharmacotherapeutic history.Of the Primary Care structures, 46% participate in clinical research on quality pharmacotherapy, and 42%of the SFAPs participate in Ethical and Research Committees. Moreover, 99% participate with Pharmacovigilanceand with programmes that promote the safe use of medicines. Of the SFAPs 41% promote educational programmesfor the population on medication. Nearly half of the SFAPs, namely 45%, already participate in strategic plans forquality in the primary care management structures. Discussion: the Health Services should promote and watchover the development of the SFAPs, not only through the regularisation of the administrative situation of the SFAPsaccording to the Law, but also through the promotion of the development of the established functions, encouragingthe involvement of the primary care pharmacist in all the processes of the therapeutic chain, returning to thesystem joint responsibility in the quality of the care and pharmacotherapy of the patients (AU)

Construction of exact solutions by spatial translations in inhomogeneous nonlinear Schrödinger equations.

In this paper, we study a general nonlinear Schrödinger equation with a time-dependent harmonic potential. Despite the lack of translational invariance, we find a symmetry transformation that, up from any solution, produces infinitely many others that are centered on classical trajectories. The results presented here imply that, not only the center of mass of the wave packet satisfies the Ehrenfest theorem and is decoupled from the dynamics of the wave packet, but also the shape of the solution is independent of the behavior of the center of the wave. Our findings have implications on the dynamics of Bose-Einstein condensates in magnetic traps.

Structural instability of vortices in Bose-Einstein condensates.

In this paper we study a gaseous Bose-Einstein condensate and show the following: (i) A minimum value of the interaction is needed for the existence of stable persistent currents. (ii) Vorticity is not a fundamental invariant of the system, as there exists a conservative mechanism which can destroy a vortex and change its sign. (iii) This mechanism is suppressed by strong interactions.

Multipole spatial vector solitons.

We introduce the concept of multipole spatial optical vector solitons associated with higher-order guided modes trapped by a soliton-induced waveguide in a bulk medium. Such stationary localized waves include previously predicted vortex- and dipole-mode vector solitons and also describe new higher-order vector solitons and necklace-type beams. We present the theoretical and experimental results of the structure, formation, and instability development of the quadrupole vector solitons.

Vortex revivals with trapped light.

We predict that vortex dipoles nested in light beams trapped in graded-index media can undergo closed Berry trajectories, yielding periodic vortex annihilations and revivals along the light-propagation direction. The vortex revivals from vortex-free wave fronts are mediated by Freund stationary point bundles that carry the necessary Poincaré-Hopf indices. Vortex spiraling and spontaneous generation of circular-edge dislocations are also found to occur.