Characterization of a c-Rel Inhibitor That Mediates Anticancer Properties in Hematologic Malignancies by Blocking NF-κB-Controlled Oxidative Stress Responses.

NF-κB plays a variety of roles in oncogenesis and immunity that may be beneficial for therapeutic targeting, but strategies to selectively inhibit NF-κB to exert antitumor activity have been elusive. Here, we describe IT-901, a bioactive naphthalenethiobarbiturate derivative that potently inhibits the NF-κB subunit c-Rel. IT-901 suppressed graft-versus-host disease while preserving graft-versus-lymphoma activity during allogeneic transplantation.

The Risk of Seizure After Surgery for Unruptured Intracranial Aneurysms: A Prospective Cohort Study.

Background: We aimed to identify a group of patients with a low risk of seizure after surgery for unruptured intracranial aneurysms (UIA).

Objective: To determine the risk of seizure after discharge from surgery for UIA.

Methods: A consecutive prospectively collected cohort database was interrogated for all surgical UIA cases.

Complication-Effectiveness Analysis for Brain Arteriovenous Malformation Surgery: A Prospective Cohort Study.

Background: Intervention for brain arteriovenous malformations (bAVMs) should aim at treatment that is safe and effective.

Objective: To analyze a prospective database to derive the probability of neurological deficit and adjust this risk for effectively treated bAVMs (complication-effectiveness analysis [CEA]).

Methods: First, we calculated the percentage of surgical complications leading to a modified Rankin Scale >1 at 12 months after surgery for each Spetzler-Ponce class (SPC).

Factors Associated With Proximal Intracranial Aneurysms to Brain Arteriovenous Malformations: A Prospective Cohort Study.

Background: The risk of hemorrhage from a brain arteriovenous malformation (bAVM) is increased when an associated proximal intracranial aneurysm (APIA) is present. Identifying factors that are associated with APIA may influence the prediction of hemorrhage in patients with bAVM.

Objective: To identify patient- and bAVM-specific factors associated with APIA.

Complication-Effectiveness Analysis for Unruptured Intracranial Aneurysm Surgery: A Prospective Cohort Study.

Background: The aim of intervention for unruptured intracranial aneurysms (UIAs) is safe, effective treatment.

Objective: To analyze a prospective database for variables influencing the risk of surgery to produce a risk model adjusting this risk for effectively treated aneurysms.

Methods: First, we identified variables to create a model from multiple logistic regression for complications of surgery leading to a 12-month modified Rankin Scale score >1.

Correlating Surrogate Endpoints with Overall Survival at the Individual Patient Level in BRAFV600E-Mutated Metastatic Melanoma Patients Treated with Vemurafenib.

Purpose: Surrogate endpoints are needed that correlate with overall survival (OS). We analyzed individual patient tumor data from a phase III trial of vemurafenib versus dacarbazine (BRIM3) to identify criteria for tumor measures that correlated with OS. Correlates were validated using a separate data set from a phase II trial of vemurafenib (BRIM2).

Effect of baseline exercise capacity on outcomes in patients with stable coronary heart disease (a post hoc analysis of the clinical outcomes utilizing revascularization and aggressive drug evaluation trial).

The impact of baseline exercise capacity on clinical outcomes in patients with stable ischemic heart disease randomized to an initial strategy of optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI) in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial has not been studied. A post hoc analysis was performed in 1,052 patients of COURAGE (PCI + OMT: n = 527, OMT: n = 525) who underwent exercise treadmill testing at baseline. Patients were categorized into 2 exercise capacity groups based on metabolic equivalents (METs) achieved during baseline exercise treadmill testing (<7 METs: n = 464, ≥7 METs: n = 588) and were followed for a median of 4.

Case Numbers and Process Quality in Breast Surgery in Germany: A Retrospective Analysis of Over 150,000 Patients From 2013 to 2014.

Background: Numerous studies from around the world have shown a positive association between case numbers and the quality of medical care. The evidence to date suggests that conformity to guidelines for the treatment of patients with breast cancer is better in German hospitals that have higher case numbers.

Methods: We used data obtained by an external program for quality assurance in inpatient care (externe stationäre Qualitätssicherung, esQS) for the years 2013 and 2014 to investigate seven process indicators in the area of breast surgery, including histologic confirmation of the diagnosis before definitive treatment, axillary dissection as recommended by the guidelines, and an appropriate temporal interval between diagnosis and operation.

A mass shooting at Port Arthur, Tasmania, Australia: a study of its impact on early pregnancy losses using a conception time-based methodology.

Study Question: Does an acute calamity in a community cause early miscarriage and is this association the same for male and female fetuses?

Summary Answer: Estimated losses of 29.5% of first trimester pregnancies in the affected region could be associated with an acute calamity, with no statistically significant difference in estimated losses by fetal sex.

What Is Known Already: There are very few studies on the impact of a calamity on early pregnancy loss and its differential effects on male and female fetuses.

Targeting disordered proteins with small molecules using entropy.

The human proteome includes many disordered proteins. Although these proteins are closely linked with a range of human diseases, no clinically approved drug targets them in their monomeric forms. This situation arises, at least in part, from the current lack of understanding of the mechanisms by which small molecules bind proteins that do not fold into well-defined conformations.

Statistical controversies in clinical research: an initial evaluation of a surrogate end point using a single randomized clinical trial and the Prentice criteria.

Surrogate end point research has grown in recent years with the increasing development and usage of biomarkers in clinical research. Surrogacy analysis is derived through randomized clinical trial data and it is carried out at the individual level and at the trial level. A common surrogate analysis at the individual level is the application of the Prentice criteria.

Proceedings of the ASNC cardiac PET summit meeting, May 12 2014, Baltimore MD : 4. Novel applications of cardiovascular PET.

While it is well recognized that cardiac PET has the ability to accurately detect myocardial ischemia and coronary blood flow, there are multiple other novel and clinically important cardiac applications of PET which are now available for the evaluation of various disease processes of the cardiovascular system. Many of these applications utilize F18-fluorodeoxyglucose (FDG), a glucose analog which is retained within cells with a high metabolic activity and which has been used extensively in nuclear medicine to evaluate oncology patients and has recently also been used to evaluate infections. This review provides an overview of some of the clinically available novel applications, Figure 1, in cardiac PET which were discussed at the American Society of Nuclear Cardiology Cardiac PET Summit, May 12, 2014.

Everolimus combined with gefitinib in patients with metastatic castration-resistant prostate cancer: Phase 1/2 results and signaling pathway implications.

Background: The effects of mammalian target of rapamycin (mTOR) inhibition are limited by feedback reactivation of receptor tyrosine kinase signaling in phosphatase and tensin homolog-null tumors. Thus, this study tested the combination of mTOR inhibition (everolimus) and epidermal growth factor receptor inhibition (gefitinib) in castration-resistant prostate cancer (CRPC).

Methods: In phase 1, 12 patients (10 with CRPC and 2 with glioblastoma) received daily gefitinib (250 mg) with weekly everolimus (30, 50, or 70 mg).

A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer.

Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of (89)Zr-DFO-huJ591 ((89)Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology.

Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of (89)Zr-J591.

A Statistical Method for the Analysis of Speech Intelligibility Tests.

Speech intelligibility tests are conducted on hearing-impaired people for the purpose of evaluating the performance of a hearing device under varying listening conditions and device settings or algorithms. The speech reception threshold (SRT) is typically defined as the signal-to-noise ratio (SNR) at which a subject scores 50% correct on a speech intelligibility test. An SRT is conventionally measured with an adaptive procedure, in which the SNR of successive sentences is adjusted based on the subject's scores on previous sentences.

How Do Noninvasive Imaging Facilities Perceive the Accreditation Process? Results of an Intersocietal Accreditation Commission Survey.

The Intersocietal Accreditation Commission (IAC) accredits vascular, echocardiography, nuclear medicine, computed tomography, and magnetic resonance imaging laboratories. How facilities involved in the accreditation process view accreditation is unknown. The objective of this study was to examine the perception of laboratory accreditation from those who had undergone the process.

Estimating the concordance probability in a survival analysis with a discrete number of risk groups.

A clinical risk classification system is an important component of a treatment decision algorithm. A measure used to assess the strength of a risk classification system is discrimination, and when the outcome is survival time, the most commonly applied global measure of discrimination is the concordance probability. The concordance probability represents the pairwise probability of lower patient risk given longer survival time.

Epigenetic down-regulation of integrin α7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a devastating malignancy characterized by invasive growth and rapid recurrence. The identification and inhibition of molecular components leading to this migratory and invasive phenotype are thus essential. Accordingly, a genome-wide expression array analysis was performed on MPM cell lines and a set of 139 genes was identified as differentially expressed in cells with high versus low migratory activity.

Quartz microbalance technology for probing biomolecular interactions.

Quartz crystal microbalance with dissipation monitoring (QCM-D) is a useful technique for observing the adsorption of molecules onto a protein-functionalized surface in real time. This technique is based on relating changes in the frequency of a piezoelectric sensor chip, onto which molecules are adsorbing, to changes in mass using the Sauerbrey equation. Here, we outline the cleaning, preparation, and analysis involved in a typical QCM-D experiment, from which one can obtain mass adsorption and kinetic binding information.

Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer.

Purpose: Trials in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrogates for survival. We evaluated circulating tumor cell (CTC) enumeration as a surrogate outcome measure.

Patients And Methods: Examining CTCs alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind phase III trial of abiraterone acetate plus prednisone versus prednisone alone in patients with metastatic CRPC previously treated with docetaxel.