We retrospectively evaluated the effect of locoregional treatment (LRT) on overall survival (OS) in 300 metastatic at diagnosis (M1) prostate cancer patients. LRT was associated in univariate and ...multivariate analysis with longer OS, which remained significant for radiotherapy but not for transurethral prostatectomy. These data support further prospective evaluation of the benefit of local control in this patient population.
The optimal management of the primary tumor in metastatic at diagnosis (M1) prostate cancer (PCa) patients is not yet established. We retrospectively evaluated the effect of locoregional treatment (LRT) on overall survival (OS) hypothesizing that this could improve outcome through better local disease control and the induction of an antitumor immune response (abscopal effect).
M1 at diagnosis PCa patients referred to the Prostate Targeted Therapy Group at the Royal Marsden between June 2003 and December 2013 were identified. LRT was defined as either surgery, radiotherapy (RT) or transurethral prostatectomy (TURP) administered to the primary tumor at any time point from diagnosis to death. Kaplan–Meier analyses generated OS data. The association between LRT and OS was evaluated in univariate (UV) and multivariate (MV) Cox regression models.
Overall 300 patients were identified; 192 patients (64%) experienced local symptoms at some point during their disease course; 72 patients received LRT (56.9% TURP, 52.7% RT). None of the patients were treated with prostatectomy. LRT was more frequently performed in patients with low volume disease (35.4% vs. 16.2%; P < .001), lower prostate-specific antigen (PSA) level at diagnosis (median PSA: 75 vs. 184 ng/mL; P = .005) and local symptoms (34.2% vs. 4.8%; P < .001). LRT was associated in UV and MV analysis with longer OS (62.1 vs. 55.8 months; hazard ratio HR, 0.74; P = .044), which remained significant for RT (69.4 vs. 55.1 months; HR, 0.54; P = .002) but not for TURP. RT was associated with better OS independent of disease volume at diagnosis.
These data support the conduct of randomized phase III trials to evaluate the benefit of local control in patients with M1 disease at diagnosis.
In this article, we analyze the relationship between the main dimensions of organizational structure (i.e., formalization, centralization, and complexity) and ecological responsiveness in a sample of ...109 firms in the European air passenger transport industry. Broadly confirming our hypotheses, the results show that high formalization of routine tasks favors ecological responsiveness. Structures characterized by high decentralization and low complexity also favor ecological responsiveness. Furthermore, decentralization has a significant, positive relationship with ecological responsiveness among firms with low vertical complexity. Overall, the results indicate that organizational structure plays a major role in ecological responsiveness.
The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their ...evolution in a study covering the years 1993–2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25‐year study period. HT rate was higher in men, although this decreased over the 25‐year study period. Type of heart disease differed in men versus women (p < .001): ischemic heart disease 47.6% versus 22.5%, dilated cardiomyopathy 41.3% versus 34.6%, or other 36% versus 17.8%, respectively. Men were more frequently diabetics (18% vs. 13.1% p < .001), hypertensives (33.1% vs. 24% p < .001), and smokers (21.7% vs. 12.9% p < .001), respectively. Women had more pre‐HT malignancies (7.1% vs. 2.8% p < .001), and their clinical status was worse at HT due to renal function and mechanical ventilation. Adjusted survival (p = .198) and most of the mortality‐related variables were similar in men and women. Death occurred more frequently in women due to rejection (7.9% vs. 5.1% p < .001) and primary failure (18.2% vs. 12.5% p < .001) and in men due to malignancies (15.1% vs. 6.6% p < .001).
Abstract Individuals with substance dependence (ISD) frequently show signs of impaired emotion processing, self-regulation and decision-making, even after prolonged abstinence from drug use and ...partial recovery of other neuropsychological functions. These impairments have been associated with alterations in the orbitofrontal cortex (OFC) in lesion and imaging studies. The aim of this study was to examine the performance of a group of ISD, who had been abstinent for at least 4 months, on a series of emotional perception, self-regulation and decision-making tests sensitive to OFC dysfunction. Thirty ISD (poly-substance abusers in their first year of abstinence) and 35 healthy comparison (HC) participants were in the study. We administered the Ekman Faces Test (EFT), the Revised Strategy Application Test (R-SAT) and the Iowa Gambling Task (IGT) to both ISD and HC. Results showed that the ISD presented significant deficits in the recognition of facial emotional expressions and decision-making as measured by the EFT and the IGT. The ISD also showed poorer strategy awareness, impaired self-regulation and higher impulsivity on the R-SAT. We found significant correlations between the different measures linked to OFC functioning. We did not find significant correlations between length of abstinence and performance on these tests. These results suggest that the evaluation of emotion, self-regulation and decision-making contributes greatly to the characterization of the persistent deficits exhibited by ISD during prolonged abstinence.
Despite the development of new therapies in the last few years, metastatic prostate cancer (PCa) is still a lethal disease. Radium-223 (Ra-223) is approved for patients with advanced ...castration-resistant prostate cancer (CRPC) with bone metastases and no visceral disease. However, patients' outcomes are heterogenous, and there is lack of validated predictive biomarkers of response, while biomarkers for early identification of patients who benefit from treatment are limited. This case report describes a remarkable and durable response to Ra-223 in a CRPC patient with bone metastases who had rapidly progressed to many previous therapies; this response is now lasting for 5 years even after having stopped backbone androgen deprivation therapy (ADT). Here, we present the clinical course of this exceptional response, as well as comprehensive genomic and histopathology analyses on sequential biopsies acquired before and after therapy. Additionally, we review current knowledge on predictive and response biomarkers to Ra-223 in metastatic prostate cancer.
Most studies focused on measuring environmental attitudes consider a one-dimension measure of pro/anti-environmentalism, such as NEP scale. Nevertheless, more recent research has shown that it seems ...more adequate to use a multidimensional approach when assessing complex relations among people and the natural environment, particularly on cultural basis. This paper aims to test the psychometric properties of the Multidimensional Environmental Concern Scale (MECS) and, in particular, its factorial invariance.
Two studies were conducted. The first one assessed factorial invariance using two different approaches (multiple group confirmatory factor analysis - MGCFA, and alignment method) in a sample of 907 undergraduate students from Argentina, India, and Spain. A second study was conducted with 557 adults from Mexico and Spain, which also evaluated the criterion validity of the MECS' scores.
The results obtained allowed to assure an acceptable degree of invariance of the MECS among all countries, and in terms of gender (Studies 1 and 2), age and education level (Study 2).
Results provide support for a multidimensional approach when studying the environmental concern, showing that the environmentalism presents different associations depending on the analysed country. A deep analysis on different conceptualization of environmentalism will be promoted.
Lipid peroxidation is a process which is key in cell signaling and disease, it is exploited in cancer therapy in the form of photodynamic therapy. The appearance of hydrophilic moieties within the ...bilayer's hydrocarbon core will dramatically alter the structure and mechanical behavior of membranes. Here, we combine viscosity sensitive fluorophores, advanced microscopy, and X-ray diffraction and molecular simulations to directly and quantitatively measure the bilayer's structural and viscoelastic properties, and correlate these with atomistic molecular modelling. Our results indicate an increase in microviscosity and a decrease in the bending rigidity upon peroxidation of the membranes, contrary to the trend observed with non-oxidized lipids. Fluorescence lifetime imaging microscopy and MD simulations give evidence for the presence of membrane regions of different local order in the oxidized membranes. We hypothesize that oxidation promotes stronger lipid-lipid interactions, which lead to an increase in the lateral heterogeneity within the bilayer and the creation of lipid clusters of higher order.
Background
Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin ...inhibitor, is increasingly used for anticoagulation in patients with non‐valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab.
Aim
To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT.
Methods
Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery.
Results
Fifty‐three patients were included (81.1% male). 7.5% required re‐operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30‐day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post‐HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post‐HT death was associated with bleeding.
Conclusions
These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations.
Jacobsen syndrome or JBS (OMIM #147791) is a contiguous gene syndrome caused by a deletion affecting the terminal q region of chromosome 11. The phenotype of patients with JBS is a specific syndromic ...phenotype predominately associated with hematological alterations. Complete and partial JBS are differentiated depending on which functional and causal genes are haploinsufficient in the patient. We describe the case of a 6-year-old Bulgarian boy in which it was possible to identify all of the major signs and symptoms listed by the Online Mendelian Inheritance in Man (OMIM) catalog using the Human Phenotype Ontology (HPO). Extensive blood and marrow tests revealed the existence of thrombocytopenia and leucopenia, specifically due to low levels of T and B cells and low levels of IgM. Genetic analysis using whole-genome single nucleotide polymorphisms (SNPs)/copy number variations (CNVs) microarray hybridization confirmed that the patient had the deletion arrhg1911q24.3q25(128,137,532-134,938,470)x1 in heterozygosis. This alteration was considered causal of partial JBS because the essential
and
genes were not included, though 30 of the 96 HPO identifiers associated with this OMIM were identified in the patient. The deletion of the
,
,
and
genes was considered to be directly associated with the immunodeficiency exhibited by the patient. Although immunodeficiency is widely accepted as a major sign of JBS, only constipation, bone marrow hypocellularity and recurrent respiratory infections have been included in the HPO as terms used to refer to the immunological defects in JBS. Exhaustive functional analysis and individual monitoring are required and should be mandatory for these patients.
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