Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in ...longer overall survival than that with ADT alone.
We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone.
A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval CI, 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%.
Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.).
Background
Diagnosing atrial fibrillation (AF) before ischemic stroke occurs is a priority for stroke prevention in AF. Smartphone camera–based photoplethysmographic (PPG) pulse waveform measurement ...discriminates between different heart rhythms, but its ability to diagnose AF in real‐world situations has not been adequately investigated. We sought to assess the diagnostic performance of a standalone smartphone PPG application, Cardiio Rhythm, for AF screening in primary care setting.
Methods and Results
Patients with hypertension, with diabetes mellitus, and/or aged ≥65 years were recruited. A single‐lead ECG was recorded by using the AliveCor heart monitor with tracings reviewed subsequently by 2 cardiologists to provide the reference standard. PPG measurements were performed by using the Cardiio Rhythm smartphone application. AF was diagnosed in 28 (2.76%) of 1013 participants. The diagnostic sensitivity of the Cardiio Rhythm for AF detection was 92.9% (95% CI 77–99%) and was higher than that of the AliveCor automated algorithm (71.4% 95% CI 51–87%). The specificities of Cardiio Rhythm and the AliveCor automated algorithm were comparable (97.7% 95% CI: 97–99% versus 99.4% 95% CI 99–100%). The positive predictive value of the Cardiio Rhythm was lower than that of the AliveCor automated algorithm (53.1% 95% CI 38–67% versus 76.9% 95% CI 56–91%); both had a very high negative predictive value (99.8% 95% CI 99–100% versus 99.2% 95% CI 98–100%).
Conclusions
The Cardiio Rhythm smartphone PPG application provides an accurate and reliable means to detect AF in patients at risk of developing AF and has the potential to enable population‐based screening for AF.
A long‐standing goal in scene understanding is to obtain interpretable and editable representations that can be directly constructed from a raw monocular RGB‐D video, without requiring specialized ...hardware setup or priors. The problem is significantly more challenging in the presence of multiple moving and/or deforming objects. Traditional methods have approached the setup with a mix of simplifications, scene priors, pretrained templates, or known deformation models. The advent of neural representations, especially neural implicit representations and radiance fields, opens the possibility of end‐to‐end optimization to collectively capture geometry, appearance, and object motion. However, current approaches produce global scene encoding, assume multiview capture with limited or no motion in the scenes, and do not facilitate easy manipulation beyond novel view synthesis. In this work, we introduce a factored neural scene representation that can directly be learned from a monocular RGB‐D video to produce object‐level neural presentations with an explicit encoding of object movement (e.g., rigid trajectory) and/or deformations (e.g., nonrigid movement). We evaluate ours against a set of neural approaches on both synthetic and real data to demonstrate that the representation is efficient, interpretable, and editable (e.g., change object trajectory). Code and data are available at: http://geometry.cs.ucl.ac.uk/projects/2023/factorednerf/.
Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it ...impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.
Parkinson disease (PD) is a progressive, neurodegenerative movement disorder with symptoms reflecting various impairments and functional limitations, such as postural instability, gait disturbance, ...immobility and falls. In addition to pharmacological and surgical management of PD, exercise and physical therapy interventions are also being actively researched. This Review provides an overview of the effects of PD on physical activity - including muscle weakness, reduced aerobic capacity, gait impairment, balance disorders and falls. Previously published reviews have discussed only the short-term benefits of exercises and physical therapy for people with PD. However, owing to the progressive nature of PD, the present Review focuses on the long-term effects of such interventions. We also discuss exercise-induced neuroplasticity, present data on the possible risks and adverse effects of exercise training, make recommendations for clinical practice, and describe new treatment approaches. Evidence suggests that a minimum of 4 weeks of gait training or 8 weeks of balance training can have positive effects that persist for 3-12 months after treatment completion. Sustained strength training, aerobic training, tai chi or dance therapy lasting at least 12 weeks can produce long-term beneficial effects. Further studies are needed to verify disease-modifying effects of these interventions.
Summary Background A subset of patients with metastatic renal-cell carcinoma show indolent growth of metastases. Because of the toxicity and non-curative nature of systemic therapy, some of these ...patients could benefit from initial active surveillance. We aimed to characterise the time to initiation of systemic therapy in patients with metastatic renal-cell carcinoma under active surveillance. Methods In this prospective phase 2 trial, we enrolled patients with treatment-naive, asymptomatic, metastatic renal-cell carcinoma from five hospitals in the USA, Spain, and the UK. Patients were radiographically assessed at baseline, every 3 months for year 1, every 4 months for year 2, then every 6 months thereafter. Patients continued on observation until initiation of systemic therapy for metastatic renal-cell carcinoma; a decision that was made at the discretion of the treating physician and patient. The primary endpoint of the study was time to initiation of systemic therapy in the per-protocol population. The follow-up of patients is ongoing. Findings Between Aug 21, 2008, and June 7, 2013, we enrolled 52 patients. Median follow-up of patients in the study was 38·1 months (IQR 29·4–48·9). In the 48 patients included in analysis, median time on surveillance from registration on study until initiation of systemic therapy was 14·9 months (95% CI 10·6–25·0). Multivariate analysis showed that higher numbers of International Metastatic Database Consortium (IMDC) adverse risk factors (p=0·0403) and higher numbers of metastatic disease sites (p=0·0414) were associated with a shorter surveillance period. 22 (46%) patients died during the study period, all from metastatic renal-cell carcinoma. Interpretation A subset of patients with metastatic renal-cell carcinoma can safely undergo surveillance before starting systemic therapy. Additional investigation is required to further define the benefits and risks of this approach. Funding None.
...acute infection by the protozoan Toxoplasma gondii leads to a break in immune tolerance toward commensal bacteria by inducing the differentiation of microbiota-reactive T cells 13. ...while IBD ...does not appear to be transmissible, intestinal microbes likely play active roles in inducing IBD. Monogenic forms of IBD exist in which rare mutations (such as in the IL-10 receptor) lead to severe disease in early life, but incomplete penetrance and interindividual heterogeneity suggest environmental variables are important 15. ...a generally accepted paradigm for IBD pathogenesis is that environmental factors and intestinal microbiota conspire to induce inflammation in genetically susceptible individuals. MNV can compensate for the absence of certain bacteria by promoting intestinal development, lymphocyte function, and resistance to injury 25. ...MNV provides similar cues to the host as bacterial members of the microbiota and mediates a disease associated with the microbiota in a genetically susceptible host. According to the gene–microbe interactions paradigm, an infectious agent would only trigger disease in individuals harboring the cognate susceptibility variant.
PDF
