DNA damage response-related alterations define the genetic background of patients with chronic lymphocytic leukemia and chromosomal gains

[EN]The presence of chromosomal gains other than trisomy 12 suggesting a hyperdiploid karyotype is extremely rare in chronic lymphocytic leukemia (CLL) and is associated with a dismal prognosis. However, the genetic mechanisms and mutational background of these patients have not been fully explored. To improve our understanding of the genetic underpinnings of this subgroup of CLL, seven CLL patients with several chromosomal gains were sequenced using a next-generation sequencing (NGS)-targeted approach. The mutational status of 54 genes was evaluated using a custom-designed gene panel including recurrent mutated genes observed in CLL and widely associated with CLL pathogenesis. A total of 21 mutations were detected; TP53 (42.8%), ATM (28.5%), SF3B1 (28.5%), and BRAF (28.5%) were the most recurrently mutated genes. Of these mutations, 61.9% were detected in genes previously associated with a poor prognosis in CLL. Interestingly, five of the seven patients exhibited alterations in TP53 or ATM (deletion and/or mutation), genes involved in the DNA damage response (DDR), which could be related to a high genetic instability in this subgroup of patients. In conclusion, CLL patients with several chromosomal gains exhibit high genetic instability, with mutations in CLL driver genes and high-risk genetic alterations involving ATM and/or TP53 genes

Ynstruitur jubentus in exiquerenda vera Imperatoris Juxtiniani enodatione super titulo de iure naturali ... : Locus certaminis tehatrum [sic] huius Universitatis

Cartel anunciador de la lectura de la tesisCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 2016Fecha en tít.: 1774Texto con orla tip

Parálisis idiopática del nervio hipogloso. Descripción de un caso.

Introduction: Hypoglossal nerve palsy is a rare mononeuropathy. The most common etiologies are tumor, traumatic, cerebral ischemic and iatrogenic causes. Description: We present a man with idiopathic hypoglossal nerve neuropathy. The patient's age, the presence of vascular risk factors and cerebral microangiopathy, and the clinical evolution leads us to discussion about the possibility of a ischemic or diabetic mononeuropathy as the etiology of the deficit. Discussion: In previous published series of idiopathic hypoglossal nerve palsy, the age of presentation is between 20 and 45 years and the patients have a favorable evolution. The pathophysiological mechanism could be similar to Bell's palsy. In our patient the physical examination and the complementary studies were normal, diagnose the deficit as idiopathic hypoglossal nerve palsy. However, due to patient's age, the presence of multiple vascular risk factors, cerebral microangiopathy and the persistence of the symptoms, we consider the existence of a local ischemic or diabetic damage as the cause of the mononeuropathy presented, and we think that the physiopathological mechanism could be similar to other mononeuropathies, such as III or VI cranial nerve palsy. Conclusion: We present an idiopathic hypoglossal nerve palsy, but due to characteristics of our patient, we discuss an ischemic or diabetic cause of the deficit.Introducción: La parálisis del nervio hipogloso es una mononeuropatía poco fre-cuente. Las etiologías más habituales son la tumoral, la traumática, la isquémica cere-bral y la iatrogénica, Descripción: Presentamos el caso de un paciente con neuropa-tía idiopática del nervio hipogloso, en el que por edad, la presencia de factores de riesgo vascular, la microangiopaía cerebral y la evolución nos lleva a discutir acerca de la posibilidad de que se trate de una mononeuropatía isquémica o diabética como etiología del déficit. Discusión: En estudios publicados de parálisis idiopáticas del nervio hipogloso la edad de presentación se sitúa entre los 20 y 45 años y tienen una evolución y recuperación favorable, atribuyéndole un mecanismo fisiopatológico similar al de la paralisis de Bell. En nuestro caso la exploración física y las pruebas complementarias realizadas no mostraron etiología del déficit, encontrándonos ante un nuevo caso de parálisis idiopática del nervio hipogloso. Sin embargo por la edad del paciente, la presencia de múltiples factores de riesgo vascular, la microangiopía cerebral y la persistencia de la sintomatología nos hace plantear la existencia de un mecanismo local, isquémico o diabético, como causa de la mononeuropatía presen-tada y pensar que nos podemos encontrar ante un mecanismo fisiopatológico similar al producido en otras mononeuropatías, como la del III o VI par craneal. Conclusión: Presentamos una parálisis del nervio hipogloso idiopática, que por las característi-cas de nuestro paciente nos hace pensar y discuti una posible etiología isquémica o diabética del déficit

Implication of breast cancer phenotype for patients with leptomeningeal carcinomatosis

Abstract Background We aimed to study the implications of breast cancer (BC) subtypes for the development and prognosis of leptomeningeal carcinomatosis (LC). Patients and methods Data from the breast cancer patients diagnosed with LC between 2005 and 2010 were retrieved. Patients were classified in luminal A, B, HER2 positive and triple negative (TN) and their BC diagnosis, treatment, and outcome were analyzed according to each subtype. Pearson's chi-square and Fisher's exact test were used for categorical variables. Survival analyses were performed by Kaplan–Meier method and compared with the log-rank test. Results A total of 38 BC patients were identified, with a median age of 54.8 years (range 36–79). The proportion of luminal A, B, HER2 positive and TN was 18.4%, 31.6%, 26.3% and 23.7%, respectively. LC was the first evidence of metastatic disease in 5 BC patients. Twenty patients received the systemic chemotherapy, with 16 (80%) whole brain radiotherapy (WBRT). Nine patients received only WBRT. TN patients had the shorter interval between metastatic breast cancer diagnosis and the development of LC. Median survival after the diagnosis of LC (OSLC) was 2.6 months (range 1.2–6.4), and did not differ across breast cancer subtypes. In univariate analysis, performance status (ECOG = 0–2) and chemotherapy were prognostic for OSLC, but only the treatment stood as an independent prognostic factor in multivariate analysis. Conclusions Breast cancer subtype influences the timing of LC appearance, but not OSLC. Patients with LC from breast cancer should be offered systemic treatment, as it appears to associate with the improved outcome. New therapeutic strategy, including, targeted and intrathecal therapy are deserved for BC patients with LC

Acoustic insertion loss due to two dimensional periodic arrays of circular cylinders parallel to a nearby surface

The acoustical performances of regular arrays of cylindrical elements, with their axes aligned and parallel to a ground plane, have been investigated through predictions and laboratory experiments. Semi-analytical predictions based on multiple scattering theory and numerical simulations based on a boundary element formulation have been made. Measurements have been made in an anechoic chamber using arrays of (a) cylindrical acoustically-rigid scatterers (PVC pipes) and (b) thin elastic shells. Insertion loss (IL) spectra due to the arrays have been measured without and with ground planes for several receiver heights. Data and predictions have been compared. The minima in the excess attenuation spectrum i.e., attenuation maxima due to the ground alone resulting from destructive interference between direct and ground-reflected sound waves, tend to have an adverse influence on the band gaps (BG) related to a periodic array in the free field when these two effects coincide. On the other hand, the presence of rigid ground may result in an IL for an array near the ground similar to or, in the case of the first BG, greater than that resulting from a double array, equivalent to the original array plus its ground plane mirror image, in the free field.Comment: J. Acoust. Soc. Am. 130 (6), December 201

Mutation status and immunoglobulin gene rearrangements in patients from northwest and central region of Spain with chronic lymphocytic leukemia

This is an open access article distributed under the Creative Commons Attribution License.-- et al.The aim of this study was to investigate the frequency and mutation status of the immunoglobulin heavy variable chain (IGHV) in a cohort of 224 patients from northwest and central region of Spain diagnosed with chronic lymphocytic leukemia (CLL), and to correlate it with cytogenetic abnormalities, overall survival (OS) and time to first treatment (TTFT). 125 patients had mutated IGHV, while 99 had unmutated IGHV. The most frequently used IGHV family was IGHV3, followed by IGHV1 and IGHV4. The regions IGHV3-30, IGHV1-69, IGHV3-23, and IGHV4-34 were the most commonly used. Only 3.1% of the patients belonged to the subfamily IGHV3-21 and we failed to demonstrate a worse clinical outcome in this subgroup. The IGHV4 family appeared more frequently with mutated pattern, similar to IGHV3-23 and IGHV3-74. By contrast, IGHV1-69 was expressed at a higher frequency in unmutated CLL patients. All the cases from IGHV3-11 and almost all from IGHV5-51 subfamily belonged to the group of unmutated CLL.The study was partially supported by grants from the Spanish Fondo de Investigaciones Sanitarias 02/1041, FIS 09/01382, FIS 09/01543, and PI12/00281; RD12/0036/0069 from Red Tematica de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF) “Una manera de hacer Europa”; and Caja de Burgos-Banca Cívica. A. Rodrígues was fully supported by an Ayuda Predoctoral FIS de Formación en Investigacion by the Spanish Fondo de Investigaciones Sanitarias. M. Hernandez-Sanchez was partially supported by a grant from the “Fundacion Española de Hematología y Hemoterapia.” Partially supported by grants from “Proyectos de Investigacion Biomédica del SACYL” 106/A/06.Peer Reviewe

Efficacy of a Strategy for Implementing Guidelines for the Control of Cardiovascular Risk in Primary Healthcare

Background: A number of strategies exist for the implementation of clinical practice guides (CPGs). Aim: To assess the efficacy of implementing a cardiovascular risk CPG based on an educational method involving opinion leaders, and the habitual method of dissemination among primary healthcare teams. Design and Setting: Controlled, blinded, community intervention trial randomised by clusters. Methods: 21 primary healthcare centres were randomly assigned to either the intervention arm (n = 11) or the control arm (n = 10). The study subjects were patients aged ≥45 years assigned to the centres. The overall impact of the intervention was measured as the difference between the increase in the proportion of patients whose medical records showed the recording of all the variables necessary to calculate cardiovascular risk in both arms. Analyses were performed with Generalized Lineal Model on an intention-to-treat basis. Results: 917 subjects were included at the beginning of the trial (437 in the intervention arm and 480 in the control arm). 826 subjects were included in the final evaluation (436 in the intervention group and 390 in the control arm). At the end of the trial, the recording of the variables necessary for the calculation of the cardiovascular risk in the intervention group had increased more than in the control group (difference between increases 7.49% (95% CI 4.62 - 10.35)) after adjusting for confounding variables. Conclusions: Compared to the habitual method of dissemination, the implementation of this CPG using an educational method involving opinion leaders, improved the recording of the variables needed to calculate patients’ cardiovascular risk.Funding for the trial was provided by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I). Instituto de Salud Carlos III—Fondo de Investigación Sanitaria. Expediente N˚ 031216.S

Juridica Acerta ex sinuóso Imperiálium Institutiónum Océano deprompta ...

Cartel anunciador de la disertaciónCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 2016Precede al tít.: "Naturále petit Jus, benè ... Schola Régia Orcélis ..."Fecha en tít. : 1776Texto enmarcado en grab. calc.Grab. calc. de águila bicéfala:"D. Joachimus Rodriguez de Munera, Inventor. Alagarda d. et sculp. Oriolae. P.C. Tip.

De Jure Personarum placita ...

Cartel anunciador de la disertaciónCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 2016Fecha en tít. : 1780Texto enmarcado en grab. calc.Grab. calc. de águila bicéfala:"D. Joachimus Rodriguez de Munera, Inventor. Alagarda d. et sculp. Oriolae. P.C. Tip.

De Jure Personarum placita ...

Cartel anunciador de la disertaciónCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 2016Fecha en tít. : 1780Texto enmarcado en grab. calc.Grab. calc. de águila bicéfala:"D. Joachimus Rodriguez de Munera, Inventor. Alagarda d. et sculp. Oriolae. P.C. Tip.