Citations

ObjectivesTo investigate the dose‐dependent effect of androgen deprivation therapy on community‐acquired respiratory infections in patients with localized prostate cancer.MethodsWe identified 52 905 men diagnosed with localized prostate cancer within the Surveillance, Epidemiology and End Results‐Medicare database between 1991 and 2006. We compared those who did not receive androgen deprivation therapy with those who received androgen deprivation therapy within 2 years of diagnosis, calculated as monthly equivalent doses (<7, 7–11, >11 doses), or orchiectomy. Adjusted Cox hazard models were fitted to predict the risk of community‐acquired respiratory infections (acute sinusitis, acute bronchitis, [severe] pneumonia) in patients treated with medical androgen deprivation therapy versus orchiectomy versus none.ResultsOverall, 43.4% received medical androgen deprivation therapy. These patients more likely experienced respiratory events compared with those who did not receive androgen deprivation therapy or who underwent orchiectomy (62.2% vs 54.5% vs 47.8%, P < 0.001). The risk of experiencing any respiratory event increased with the number of doses received. For example, men receiving >11 doses of androgen deprivation therapy were at greatest risk of acute sinusitis, acute bronchitis and pneumonia (HR 1.13, 1.26 and 1.15, respectively, all P < 0.001), except severe pneumonia. Furthermore, we did not detect any relationship between orchiectomy and respiratory events. Study limitations include the utilization of a retrospective population‐based dataset.ConclusionsIncreased exposure to medical androgen deprivation therapy for men with localized prostate cancer is associated with a higher risk of community‐acquired respiratory infections. Our results suggest that respiratory complications represent potentially underreported complications of medical androgen deprivation therapy.

Background— Cardiac sarcoidosis is associated with an increased risk of heart failure and sudden death, but its risk in patients with preserved left ventricular ejection fraction is unknown. Using cardiovascular magnetic resonance in patients with extracardiac sarcoidosis and preserved left ventricular ejection fraction, we sought to (1) determine the prevalence of cardiac sarcoidosis or associated myocardial damage, defined by the presence of late gadolinium enhancement (LGE), (2) quantify their risk of death/ventricular tachycardia (VT), and (3) identify imaging-based covariates that predict who is at greatest risk of death/VT. Methods and Results— Parameters of left and right ventricular function and LGE burden were measured in 205 patients with left ventricular ejection fraction >50% and extracardiac sarcoidosis who underwent cardiovascular magnetic resonance for LGE evaluation. The association between covariates and death/VT in the entire group and within the LGE+ group was determined using Cox proportional hazard models and time-dependent receiver–operator curves analysis. Forty-one of 205 patients (20%) had LGE; 12 of 205 (6%) died or had VT during follow-up; of these, 10 (83%) were in the LGE+ group. In the LGE+ group (1) the rate of death/VT per year was >20× higher than LGE− (4.9 versus 0.2%, P <0.01); (2) death/VT were associated with a greater burden of LGE (14±11 versus 5±5%, P <0.01) and right ventricular dysfunction (right ventricular EF 45±12 versus 53±28%, P =0.04). LGE burden was the best predictor of death/VT (area under the receiver-operating characteristics curve, 0.80); for every 1% increase of LGE burden, the hazard of death/VT increased by 8%. Conclusions— Sarcoidosis patients with LGE are at significant risk for death/VT, even with preserved left ventricular ejection fraction. Increased LGE burden and right ventricular dysfunction can identify LGE+ patients at highest risk of death/VT.

Objectives To test the external validity of a previously developed risk table, designed to predict the probability of a positive bone scan among men with non‐metastatic (M0) castration‐resistant prostate cancer ( CRPC ), in a separate cohort. Patients and Methods We retrospectively analysed 429 bone scans of 281 patients with CRPC , with no known previous metastases, treated at three Veterans Affairs Medical Centers. We assessed the predictors of a positive scan using generalized estimating equations. Area under the curve ( AUC ), calibration plots and decision‐curve analysis were used to assess the performance of our previous model to predict a positive scan in the current data. Results A total of 113 scans (26%) were positive. On multivariable analysis, the only significant predictors of a positive scan were log‐transformed prostate‐specific antigen ( PSA ): hazard ratio ( HR ) 2.13; 95% confidence interval ( CI ) 1.71–2.66 ( P < 0.001) and log‐transformed PSA doubling time ( PSADT ): HR 0.53; 95% CI 0.41–0.68 ( P < 0.001). Among men with a PSA level <5 ng/ mL , the rate of positive scans was 5%. The previously developed risk table had an AUC of 0.735 to predict positive bone scan with excellent calibration, and provided additional net benefit in the decision‐curve analysis. Conclusion We have validated our previously developed table to predict the risk of a positive bone scan among men with M0/Mx CRPC . Use of this risk table may allow better tailoring of patients' scanning to identify metastases early, while minimizing over‐imaging. Regardless of PSADT , positive bone scans were rare in men with a PSA <5 ng/ mL .

Health care services that increase costs but fail to improve health are of low value. Limiting low-value services has potential to decrease health care expenditures by eliminating waste. We examined the opinions of Continuing Medical Education attendees about the “Choosing Wisely” campaign and decreasing use of potentially unnecessary services of low value. We compared our attendees’ responses to those of participants who completed a survey a year earlier. Respondents acknowledged waste of resources as a common and serious problem and noted frequent opportunities to address low-value services with their patients. They also reported limited ability to successfully reduce unnecessary services in daily clinical care. Lack of familiarity with “Choosing Wisely” may be related.

Abstract Glioblastoma (GB) is the highest grade and most common form of primary adult brain tumors. Despite surgical removal followed by concomitant radiation and chemotherapy with the alkylating agent temozolomide, GB tumors develop treatment resistance and ultimately recur. Impaired response to treatment occurs rapidly, conferring a median survival of just fifteen months. Thus, it is necessary to identify the genetic and signaling mechanisms that promote tumor resistance to develop targeted therapies to combat this refractory disease. Previous observations indicated that SGEF (ARHGEF26), a RhoG-specific guanine nucleotide exchange factor (GEF), is overexpressed in GB tumors and plays a role in promoting TWEAK-Fn14–mediated glioma invasion. Here, further investigation revealed an important role for SGEF in glioma cell survival. SGEF expression is upregulated by TWEAK-Fn14 signaling via NF-κB activity while shRNA-mediated reduction of SGEF expression sensitizes glioma cells to temozolomide-induced apoptosis and suppresses colony formation following temozolomide treatment. Nuclear SGEF is activated following temozolomide exposure and complexes with the DNA damage repair (DDR) protein BRCA1. Moreover, BRCA1 phosphorylation in response to temozolomide treatment is hindered by SGEF knockdown. The role of SGEF in promoting chemotherapeutic resistance highlights a heretofore unappreciated driver, and suggests its candidacy for development of novel targeted therapeutics for temozolomide-refractory, invasive GB cells. Implication: SGEF, as a dual process modulator of cell survival and invasion, represents a novel target for treatment refractory glioblastoma. Mol Cancer Res; 14(3); 302–12. ©2016 AACR.

Developing a systematic approach to hospital discharges can lead to improvements and serve a model for other inpatient wards.