Background The purpose of this analysis was to compare long-term urinary, bowel, and sexual function after radical prostatectomy or external-beam radiation therapy. Methods The Prostate Cancer Outcomes Study (PCOS) enrolled 3533 men in whom prostate cancer had been diagnosed in 1994 or 1995. The current cohort comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at 2, 5, and 15 years after diagnosis. We used multivariable propensity scoring to compare functional outcomes according to treatment. Results Patients undergoing prostatectomy were more likely to have urinary incontinence than were those undergoing radiotherapy at 2 years (odds ratio, 6.22; 95% confidence interval [CI], 1.92 to 20.29) and 5 years (odds ratio, 5.10; 95% CI, 2.29 to 11.36). However, no significant between-group difference in the odds of urinary incontinence was noted at 15 years. Similarly, although patients undergoing prostatectomy were more likely to have erectile dysfunction at 2 years (odds ratio, 3.46; 95% CI, 1.93 to 6.17) and 5 years (odds ratio, 1.96; 95% CI, 1.05 to 3.63), no significant between-group difference was noted at 15 years. Patients undergoing prostatectomy were less likely to have bowel urgency at 2 years (odds ratio, 0.39; 95% CI, 0.22 to 0.68) and 5 years (odds ratio, 0.47; 95% CI, 0.26 to 0.84), again with no significant between-group difference in the odds of bowel urgency at 15 years. Conclusions At 15 years, no significant relative differences in disease-specific functional outcomes were observed among men undergoing prostatectomy or radiotherapy. Nonetheless, men treated for localized prostate cancer commonly had declines in all functional domains during 15 years of follow-up. (Funded by the National Cancer Institute.)

The RALE score can be used to assess both the extent of pulmonary oedema and the severity of ARDS, by utilising information that is already obtained routinely, safely and inexpensively in every patient with ARDS. This novel non-invasive measure should be useful for assessing ARDS severity and monitoring response to therapy.

In patients with acute lung injury (ALI) and ARDS, clinical risk factors such as age, severity of illness scoring, and diagnosis of sepsis have a moderate predictive value for death and other adverse clinical outcomes. 1,2 Several plasma biologic markers also have predictive value for death, ventilator-free days, and duration of organ failure when considered as single biomarkers in large patient populations.

Importance Prostate cancer treatments are associated with side effects. Understanding the side effects of contemporary approaches to management of localized prostate could inform shared decision-making. Objective To compare the harms of radical prostatectomy (RP), radiation (EBRT) and active surveillance (AS). Design The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, cohort study of men diagnosed with localized prostate cancer in 2011–2012. This study reports follow up through August 2015. Setting Patients accrued from five Surveillance Epidemiology, and End Results registry sites and the Cancer of the Prostate Strategic Urologic Research Endeavor. Participants Men < 80 years old with clinical stage cT1-2 disease, prostate specific antigen < 50 ng/mL, enrolled within six months of diagnosis, who completed a baseline survey and at least 1 follow-up survey. Exposure Treatment with RP, EBRT or AS was ascertained within one year of diagnosis. Main Outcome and Measures Patient-reported function in sexual, urinary incontinence, urinary irritative, bowel, and hormonal domains on the 26-item Expanded Prostate Cancer Index Composite (EPIC) 36 months after enrollment. Domain scores range from 0–100. Higher score indicates better function. Minimum clinically important difference defined as 10–12, 6, 5, 5, and 4, respectively. Results The cohort included 2550 men (mean age 63.8 years, 74% white, 55% intermediate or high risk), of whom 1523 (59.7%) underwent RP, 598 (23.5%) EBRT, and 429 (16.8%) AS. Men undergoing EBRT were older (mean age 68.1 vs. 61.5, p<0.001), and had worse baseline sexual function (mean EPIC domain score 52.3 vs. 65.2, p<0.001) than men undergoing RP. At 3 years, adjusted mean sexual domain score for men undergoing RP had declined more than for men undergoing EBRT (mean difference −11.9 points, 95% CI [−15.1, −8.7]). The difference in decline in sexual domain scores between EBRT and AS was not clinically significant (−4.3 points, 95% CI [−9.2, 0.7]). RP was associated with worse urinary incontinence than EBRT (−18.0 points, 95% CI [−20.5, −15.4]) or AS (−12.7 points, 95% CI [−16.0, −9.3]) and better urinary irritative symptoms compared to AS (5.2 points, 95% CI [3.2, 7.2]). No clinically significant differences for bowel or hormone function were noted beyond 12 months. No differences in global quality of life or disease-specific survival (3 deaths) were noted (99.7–100%). Conclusion and Relevance In this cohort of men with localized prostate cancer, RP was associated with a larger decline in sexual function and urinary incontinence than EBRT or AS after 3 years, and lesser urinary irritative symptoms compared to AS; however, there were no meaningful differences in bowel or hormonal function beyond 12 months and no meaningful differences in global quality of life measures. These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer.

IMPORTANCE Understanding adverse effects of contemporary treatment approaches for men with favorable-risk and unfavorable-risk localized prostate cancer could inform treatment selection. OBJECTIVE To compare functional outcomes associated with prostate cancer treatments over 5 years after treatment. DESIGN, SETTING, AND PARTICIPANTS Prospective, population-based cohort study of 1386 men with favorable-risk (clinical stage cT1 to cT2bN0M0, prostate-specific antigen [PSA] Յ20 ng/mL, and Grade Group 1-2) prostate cancer and 619 men with unfavorable-risk (clinical stage cT2cN0M0, PSA of 20-50 ng/mL, or Grade Group 3-5) prostate cancer diagnosed in 2011 through 2012, accrued from 5 Surveillance, Epidemiology and End Results Program sites and a US prostate cancer registry, with surveys through September 2017. EXPOSURES Treatment with active surveillance (n = 363), nerve-sparing prostatectomy (n = 675), external beam radiation therapy (EBRT; n = 261), or low-dose-rate brachytherapy (n = 87) for men with favorable-risk disease and treatment with prostatectomy (n = 402) or EBRT with androgen deprivation therapy (n = 217) for men with unfavorable-risk disease. MAIN OUTCOMES AND MEASURES Patient-reported function, based on the 26-item Expanded Prostate Index Composite (range, 0-100), 5 years after treatment. Regression models were adjusted for baseline function and patient and tumor characteristics. Minimum clinically important difference was 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritative symptoms, and 4 to 6 for bowel and hormonal function. RESULTS A total of 2005 men met inclusion criteria and completed the baseline and at least 1 postbaseline survey (median [interquartile range] age, 64 [59-70] years; 1529 of 1993 participants [77%] were non-Hispanic white). For men with favorable-risk prostate cancer, nerve-sparing prostatectomy was associated with worse urinary incontinence at 5 years

IntroductionDespite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.MethodsThis was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.ResultsUsing the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.ConclusionsAbnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.

The purpose of this study was to determine the efficacy of a cognitive-behavioral based physical therapy (CBPT) program for improving outcomes in patients following lumbar spine surgery. A randomized controlled trial was conducted in 86 adults undergoing a laminectomy with or without arthrodesis for a lumbar degenerative condition. Patients were screened preoperatively for high fear of movement using the Tampa Scale for Kinesiophobia. Randomization to either CBPT or an Education program occurred at 6 weeks after surgery. Assessments were completed pre-treatment, post-treatment and at 3 month follow-up. The primary outcomes were pain and disability measured by the Brief Pain Inventory and Oswestry Disability Index. Secondary outcomes included general health (SF-12) and performance-based tests (5-Chair Stand, Timed Up and Go, 10 Meter Walk). Multivariable linear regression analyses found that CBPT participants had significantly greater decreases in pain and disability and increases in general health and physical performance compared to the Education group at 3 month follow-up. Results suggest a targeted CBPT program may result in significant and clinically meaningful improvement in postoperative outcomes. CBPT has the potential to be an evidence-based program that clinicians can recommend for patients at-risk for poor recovery following spine surgery.

TGF-β is an important paracrine factor in tumorigenesis. Ligand binding of the type I and II TGF-β receptors initiate downstream signaling. The role of stromal TGF-β signaling in prostate cancer progression is unknown. In mice the conditional stromal knockout of the TGF-β receptor type II expression (Tgfbr2fspKO) resulted in the development of prostatic intraepithelial neoplasia and progression to adenocarcinoma within seven months. Clinically, we observed a loss of TGF-β receptor type II expression in 69% of human prostate cancer-associated stroma compared to 15% of stroma associated with benign tissues (n =140, p value < 0.0001). To investigate the mechanism of paracrine TGF-β signaling in prostate cancer progression, we compared the effect of the prostatic stromal cells from Tgfbr2fspKO and Tgfbr2floxE2/floxE2 mice on LNCaP human prostate cancer cells in vitro and tissue recombination xenografts. Induction of LNCaP cell proliferation and tumorigenesis was observed by Tgfbr2fspKO prostate stroma as a result of elevated Wnt3a expression. Neutralizing antibodies to Wnt3a reversed LNCaP tumorigenesis. The TGF-β inhibition of Wnt3a expression was in part through the suppression of Stat3 activity on the Wnt3a promoter. In conclusion, the frequent loss of stromal TβRII expression in human prostate cancer can relieve the paracrine suppression of Wnt3a expression.