Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle‐invasive and advanced bladder cancer has primarily consisted of ...platinum‐based chemotherapy. Over the past 10 years, innovations in sequencing technologies have led to rapid genomic characterization of bladder cancer, deepening our understanding of bladder cancer pathogenesis and exposing potential therapeutic vulnerabilities. On the basis of its high mutational burden, immune checkpoint inhibitors were investigated in advanced bladder cancer, revealing durable responses in a subset of patients. These agents are now approved for several indications and highlight the changing treatment landscape of advanced bladder cancer. In addition, commonly expressed molecular targets were leveraged to develop targeted therapies, such as fibroblast growth factor receptor inhibitors and antibody‐drug conjugates. The molecular characterization of bladder cancer and the development of novel therapies also have stimulated investigations into optimizing treatment approaches for muscle‐invasive bladder cancer. Herein, the authors review the history of muscle‐invasive and advanced bladder cancer management, highlight the important molecular characteristics of bladder cancer, describe the major advances in treatment, and offer future directions for therapeutic development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Summary
Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is ...associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD.
Purpose
Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD.
Methods
We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by
T
score: normal (
T
score ≥ − 1.0), osteopenia (− 1.0 >
T
score > − 2.5), and osteoporosis (
T
score ≤ − 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (
T
score < − 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD).
Results
Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12 years; male 61%). Over a median follow-up of 4.3 years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49–0.77)) and spot urine Na/K ratio (1.07 (1.00–1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92–1.41) for osteopenia; 1.43 (1.01–2.04) for osteoporosis,
P
for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to
T
score discordance classification.
Conclusions
Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The summary presented herein represents Part I of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients ...with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. Please refer to Part II for discussion of the management of castration-resistant disease.
The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.
The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1Figure: see text and detailed herein.
This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.
The Korea National Health and Nutrition Examination Survey (KNHANES) is a national surveillance system that has been assessing the health and nutritional status of Koreans since 1998. Based on the ...National Health Promotion Act, the surveys have been conducted by the Korea Centers for Disease Control and Prevention (KCDC). This nationally representative cross-sectional survey includes approximately 10 000 individuals each year as a survey sample and collects information on socioeconomic status, health-related behaviours, quality of life, healthcare utilization, anthropometric measures, biochemical and clinical profiles for non-communicable diseases and dietary intakes with three component surveys: health interview, health examination and nutrition survey. The health interview and health examination are conducted by trained staff members, including physicians, medical technicians and health interviewers, at a mobile examination centre, and dieticians' visits to the homes of the study participants are followed up. KNHANES provides statistics for health-related policies in Korea, which also serve as the research infrastructure for studies on risk factors and diseases by supporting over 500 publications. KCDC has also supported researchers in Korea by providing annual workshops for data users. KCDC has published the Korea Health Statistics each year, and microdata are publicly available through the KNHANES website (http://knhanes.cdc.go.kr).
We characterize the environments of local accreting supermassive black holes by measuring the clustering of AGNs in the Swift/BAT Spectroscopic Survey (BASS). With 548 AGN in the redshift range 0.01 ...< z < 0.1 over the full sky from the DR1 catalog, BASS provides the largest, least biased sample of local AGNs to date due to its hard X-ray selection (14-195 keV) and rich multiwavelength/ancillary data. By measuring the projected cross-correlation function between the AGN and 2MASS galaxies, and interpreting it via halo occupation distribution and subhalo-based models, we constrain the occupation statistics of the full sample, as well as in bins of absorbing column density and black hole mass. We find that AGNs tend to reside in galaxy group environments, in agreement with previous studies of AGNs throughout a large range of luminosity and redshift, and that on average they occupy their dark matter halos similar to inactive galaxies of comparable stellar mass. We also find evidence that obscured AGNs tend to reside in denser environments than unobscured AGNs, even when samples were matched in luminosity, redshift, stellar mass, and Eddington ratio. We show that this can be explained either by significantly different halo occupation distributions or statistically different host halo assembly histories. Lastly, we see that massive black holes are slightly more likely to reside in central galaxies than black holes of smaller mass.
Hard X-ray (≥10 keV) observations of active galactic nuclei (AGNs) can shed light on some of the most obscured episodes of accretion onto supermassive black holes. The 70-month Swift/BAT all-sky ...survey, which probes the 14-195 keV energy range, has currently detected 838 AGNs. We report here on the broadband X-ray (0.3-150 keV) characteristics of these AGNs, obtained by combining XMM-Newton, Swift/XRT, ASCA, Chandra, and Suzaku observations in the soft X-ray band ( keV) with 70-month averaged Swift/BAT data. The nonblazar AGNs of our sample are almost equally divided into unobscured ( ) and obscured ( ) AGNs, and their Swift/BAT continuum is systematically steeper than the 0.3-10 keV emission, which suggests that the presence of a high-energy cutoff is almost ubiquitous. We discuss the main X-ray spectral parameters obtained, such as the photon index, the reflection parameter, the energy of the cutoff, neutral and ionized absorbers, and the soft excess for both obscured and unobscured AGNs.
ABSTRACT
Accreting supermassive black holes (SMBHs), also known as active galactic nuclei (AGN), are generally surrounded by large amounts of gas and dust. This surrounding material reprocesses the ...primary X-ray emission produced close to the SMBH and gives rise to several components in the broadband X-ray spectra of AGN, including a power-law possibly associated with Thomson-scattered radiation. In this work, we study the properties of this scattered component for a sample of 386 hard-X-ray-selected, nearby ($z\sim0.03$) obscured AGN from the 70-month Swift/BAT catalogue. We investigate how the fraction of Thomson-scattered radiation correlates with different physical properties of AGN, such as line-of-sight column density, X-ray luminosity, black hole mass, and Eddington ratio. We find a significant negative correlation between the scattering fraction and the column density. Based on a large number of spectral simulations, we exclude the possibility that this anticorrelation is due to degeneracies between the parameters. The negative correlation also persists when considering different ranges of luminosity, black hole mass, and Eddington ratio. We discuss how this correlation might be either due to the angle dependence of the Thomson cross-section or to more obscured sources having a higher covering factor of the torus. We also find a positive correlation between the scattering fraction and the ratio of O iii λ5007 to X-ray luminosity. This result is consistent with previous studies and suggests that the Thomson-scattered component is associated with the narrow-line region.
Abstract Background In patients with severe aortic stenosis at increased risk for surgery, self-expanding transcatheter aortic valve replacement (TAVR) is associated with improved 2-year survival ...compared with surgery. Objectives This study sought to determine whether this clinical benefit was sustained over time. Methods Patients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were randomized 1:1 to TAVR or open surgical valve replacement (SAVR). Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure. Results A total of 797 patients underwent randomization at 45 U.S. centers; 750 patients underwent an attempted procedure. Three-year all-cause mortality or stroke was significantly lower in TAVR patients (37.3% vs. 46.7% in SAVR; p = 0.006). Adverse clinical outcome components were also reduced in TAVR patients compared with SAVR patients, including all-cause mortality (32.9% vs. 39.1%, respectively; p = 0.068), all stroke (12.6% vs. 19.0%, respectively; p = 0.034), and major adverse cardiovascular or cerebrovascular events (40.2% vs. 47.9%, respectively; p = 0.025). At 3 years aortic valve hemodynamics were better with TAVR patients (mean aortic valve gradient 7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR; p < 0.001), although moderate or severe residual aortic regurgitation was higher in TAVR patients (6.8% vs. 0.0% in SAVR; p < 0.001). There was no clinical evidence of valve thrombosis in either group. Conclusions Patients with severe aortic stenosis at increased risk for surgery had improved 3-year clinical outcomes after TAVR compared with surgery. Aortic valve hemodynamics were more favorable in TAVR patients without differences in structural valve deterioration. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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