Abstract Prostate cancer is the most frequent cancer amongst men. Until recently, only two therapeutic options, initial androgen-deprivation therapy in patients without castration-resistant prostate ...cancer, with addition of docetaxel when the disease becomes castration-resistant, were considered as standard. In the last years, new drugs (abiraterone, enzalutamide, Ra-223, Sipuleucel) have been developed for prostate cancer treatment with important advantages in safety and efficacy. Results from the recent Chaarted study, in patients that received docetaxel for the hormone sensitive disease, have contributed to change the initial treatment approach in metastatic prostate cancer, in order to adapt the best sequence for each patient. Those results have been supported by the Stampede trial. Stampede survival data showed not only a benefit in overall survival of adding docetaxel initially, but also a prolonged time to first skeletal related event. Now it is discussed in which setting the available drugs should be administered. This review article summarizes the treatment options for patients treated with docetaxel initially for hormone sensitive prostate cancer after developing progressive disease, and offers an algorithm proposal for treatment.
Background and purpose
Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the ...neural correlates of hypomimia and the relationship between hypomimia and other non‐motor symptoms of PD are poorly understood.
Methods
The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross‐sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS‐III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used.
Results
After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS‐III speech and bradykinesia items and was significantly related to the severity of apathy (β = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto‐temporo‐parietal regions involved in the decoding, recognition and production of facial expression of emotions.
Conclusion
Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non‐motor aspects converge.
Hypomimia in Parkinson’s disease (PD) is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit where motor and non‐motor aspects converge.
We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia.
The study included ...a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models.
Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02).
Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.
•Multimodal MRI study of cognitive deficits in nondemented Parkinson's disease (PD).•Cognitive deficits in PD relate to lower cholinergic basal forebrain (CBF) volume.•Hippocampal volume not associated with cognitive deficits.•DTI diffusion measures more sensitive than volume in hippocampus but not in CBF.•Implications for the development of imaging biomarkers of cognitive decline in PD.
The role of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations as negative predictors for anti-epidermal growth factor receptor (EGFR) ...therapies in metastatic colorectal cancer (CRC) has been firmly established. However, whether the RAS mutation status plays a role as a biomarker for anti-vascular endothelial growth factor (VEGF) treatment remains controversial. Data from 93 CRC patients who received first-line cytotoxic chemotherapy with fluoropyrimidines and oxaliplatin, with or without bevacizumab, were analyzed. We investigated the association between the RAS mutation status and clinical outcomes in terms of response rate, progression-free survival (PFS) and overall survival (OS). Mutations in RAS genes were observed in 47 (52.6%) patients (45 KRAS and 2 NRAS mutations). Patients with tumours harbouring RAS mutations were less suitable for primary tumour resection, were more likely to develop lung metastases, and received bevacizumab treatment for a shorter time period compared with those with wild-type tumours. The response rate to chemotherapy did not differ according to the RAS mutation status, and there were no significant differences in PFS RAS mutation: 12 months, 95% confidence interval (CI): 8.7-15.2 vs. RAS wild-type: 12 months, 95% CI: 9.67-14.32; P=0.857 or OS (RAS mutation: 20 months, 95% CI: 14.3-25.6 vs. RAS wild-type: 24 months, 95% CI: 18.7-29.2; P=0.631). Patients with RAS mutation vs. those with RAS wild-type exhibited a favourable trend in PFS when treated with bevacizumab (13 months, 95% CI: 6.5-19.4 vs. 10 months, 95% CI: 4.2-15.7, respectively; P=0.07) and OS (27 months, 95% CI: 18.5-35.4 vs. 15 months, 95% CI: 12.4-17.5, respectively; P=0.22). In conclusion, RAS mutations are not a prognostic marker for PFS and OS in CRC patients receiving fluoropyrimidine-oxaliplatine treatment, with or without bevacizumab. RAS mutations are not predictive of the lack of efficacy of bevacizumab, and these patients appear to benefit from anti-angiogenic treatment.
This paper addresses, through a timeline, women's political rights in a democratic society. For the realization of this study, an analysis of the struggle of women for their human rights throughout ...history was conducted, beginning with the postulates of Olympe de Gouges as the starting point of feminism in the world and the fight for women's human rights.
El presente trabajo aborda a través de la línea del tiempo de los derechos políticos de las mujeres en una sociedad democrática, para la realización del estudio, se hace un análisis de la lucha de ...las mujeres por sus derechos humanos a través de la historia, dando inicio con los postulados de Olympe de Gouges como punto de partida del feminismo en el mundo y la lucha por los derechos humanos de las mujeres.
For specialists in charge of Parkinson's disease (PD), one of the most time-consuming tasks of the consultations is the assessment of symptoms and motor fluctuations. This task is complex and is ...usually based on the information provided by the patients themselves, which in most cases is complex and biased. In recent times, different tools have appeared on the market that allow automatic ambulatory monitoring. The MoMoPa-EC clinical trial (NCT04176302) investigates the effect of one of these tools-Sense4Care's STAT-ON-can have on routine clinical practice. In this sub-analysis the agreement between the Hauser diaries and the STAT-ON sensor is analyzed.
Eighty four patients from MoMoPa-EC cohort were included in this sub-analysis. The intraclass correlation coefficient was calculated between the patient diary entries and the sensor data.
The intraclass correlation coefficient of both methods was 0.57 (95% CI: 0.3-0.73) for the OFF time (%), 0.48 (95% CI: 0.17-0.68) for the time in ON (%), and 0.65 (95% CI%: 0.44-0.78) for the time with dyskinesias (%). Furthermore, the Spearman correlations with the UPDRS scale have been analyzed for different parameters of the two methods. The maximum correlation found was -0.63 (
< 0.001) between Mean Fluidity (one of the variables offered by the STAT-dON) and factor 1 of the UPDRS.
This sub-analysis shows a moderate concordance between the two tools, it is clearly appreciated that the correlation between the different UPDRS indices is better with the STAT-ON than with the Hauser diary.
https://clinicaltrials.gov/show/NCT04176302 (NCT04176302).
This paper addresses, through a timeline, women's political rights in a democratic society. For the realization of this study, an analysis of the struggle of women for their human rights throughout ...history was conducted, beginning with the postulates of Olympe de Gouges as the starting point of feminism in the world and the fight for women's human rights.
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