Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686.

Background: ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and fluid attenuated inversion recovery (FLAIR)-hyperintense tumor assessed by central reading prognosticate overall survival (OS).

Methods: Two hundred eighty-four patients (171 men; median age 57 y, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 wk post chemoradiation initiation).

Network Analysis to Risk Stratify Patients With Exercise Intolerance.

Rationale: Current methods assessing clinical risk because of exercise intolerance in patients with cardiopulmonary disease rely on a small subset of traditional variables. Alternative strategies incorporating the spectrum of factors underlying prognosis in at-risk patients may be useful clinically, but are lacking.

Objective: Use unbiased analyses to identify variables that correspond to clinical risk in patients with exercise intolerance.

Treatment of Severe Hyperkalemia: Confronting 4 Fallacies.

Severe hyperkalemia is a medical emergency that can cause lethal arrhythmias. Successful management requires monitoring of the electrocardiogram and serum potassium concentrations, the prompt institution of therapies that work both synergistically and sequentially, and timely repeat dosing as necessary. It is of concern then that, based on questions about effectiveness and safety, many physicians no longer use 3 key modalities in the treatment of severe hyperkalemia: sodium bicarbonate, sodium polystyrene sulfonate (Kayexalate [Concordia Pharmaceuticals Inc.

Nutrition Management of Home Parenteral Nutrition Among Patients With Enterocutaneous Fistula in the Sustain Registry.

Background: Home parenteral nutrition (HPN) is a vital therapy for patients who have the diagnosis of enterocutaneous fistula (ECF), yet little is known about how these patients are managed. This research compares nutrition management of adults with ECF as the indication for HPN therapy to those with other indications.

Methods: This is an analysis of data from adult HPN patients in the Sustain registry enrolled between August 2011 and February 2014 who have the diagnosis of ECF or other indication for HPN who served as the control group.

Activation of Anoctamin-1 Limits Pulmonary Endothelial Cell Proliferation via p38-Mitogen-activated Protein Kinase-Dependent Apoptosis.

Hyperproliferative endothelial cells (ECs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Anoctamin (Ano)-1, a calcium-activated chloride channel, can regulate cell proliferation and cell cycle in multiple cell types. However, the expression and function of Ano1 in the pulmonary endothelium is unknown.

Knee Alignment Is Quantitatively Related to Periarticular Bone Morphometry and Density, Especially in Patients With Osteoarthritis.

Objective: Static alignment influences knee loading and predicts osteoarthritis (OA) progression. Periarticular bone is important in dispersing forces across the knee, and there is substantial evidence for molecular crosstalk between cartilage and subchondral bone. The aim of this study was to evaluate the relationship between periarticular trabecular bone morphology and bone mineral density (BMD) and knee alignment in OA.

Smoking cessation and outcome after ischemic stroke or TIA.

Objective: To assess whether smoking cessation after an ischemic stroke or TIA improves outcomes compared to continued smoking.

Methods: We conducted a prospective observational cohort study of 3,876 nondiabetic men and women enrolled in the Insulin Resistance Intervention After Stroke (IRIS) trial who were randomized to pioglitazone or placebo within 180 days of a qualifying stroke or TIA and followed up for a median of 4.8 years.

ALOX15 Immunohistochemistry Aids in the Diagnosis of Eosinophilic Esophagitis on Pauci-eosinophilic Biopsies in Children.

Histologically, esophageal biopsies should have ≥15 intraepithelial eosinophils (IEEs) per high power field (HPF) to support a clinicopathologic diagnosis of eosinophilic esophagitis (EoE). Children with clinically apparent EoE may show pauci-eosinophilic biopsies due to patchy involvement. Immunostaining (Immunohistochemistry) for arachidonate-15 lipooxygenase (ALOX15) has been demonstrated to be a sensitive marker for EoE.

G-activated fibroblasts induce cardiomyocyte action potential prolongation and automaticity in a three-dimensional microtissue environment.

Cardiac fibroblasts (CFs) are known to regulate cardiomyocyte (CM) function in vivo and in two-dimensional in vitro cultures. This study examined the effect of CF activation on the regulation of CM electrical activity in a three-dimensional (3-D) microtissue environment. Using a scaffold-free 3-D platform with interspersed neonatal rat ventricular CMs and CFs, G-mediated signaling was selectively enhanced in CFs by Gα adenoviral infection before coseeding with CMs in nonadhesive hydrogels.

Autonomic Cardiac Function in Preclinical Alzheimer's Disease.

To explore early autonomic cardiac changes in pre-clinical Alzheimer's disease (AD), we have evaluated electrocardiologic measures of vagal tone for 63 adults (ages 55-75) at rest, during cognitive testing, and then again at rest. All subjects had multiple risk factors for AD, and all completed amyloid PET scans (18F-Florbetapir) to determine amyloid positivity (Aβ+). No change in electrocardiographic measures were observed for Aβ+ participants under each testing condition, whereas Aβ-subjects showed an expected increase in vagal tone during the cognitive stress condition.

Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling.

Background: Papillary renal cell carcinoma (PRCC) is a rare subset of RCC. The Cancer Genome Atlas (TCGA) data largely reflect localized disease, and there are limited data for advanced PRCC.

Objective: To characterize the frequency of genomic alterations (GAs) in patients with advanced PRCC for whom comprehensive genomic profiling (CGP) was performed in the context of routine clinical care.

A Population-Based Digital Reference Object (DRO) for Optimizing Dynamic Susceptibility Contrast (DSC)-MRI Methods for Clinical Trials.

The standardization and broad-scale integration of dynamic susceptibility contrast (DSC)-magnetic resonance imaging (MRI) have been confounded by a lack of consensus on DSC-MRI methodology for preventing potential relative cerebral blood volume inaccuracies, including the choice of acquisition protocols and postprocessing algorithms. Therefore, we developed a digital reference object (DRO), using physiological and kinetic parameters derived from in vivo data, unique voxel-wise 3-dimensional tissue structures, and a validated MRI signal computational approach, aimed at validating image acquisition and analysis methods for accurately measuring relative cerebral blood volume in glioblastomas. To achieve DSC-MRI signals representative of the temporal characteristics, magnitude, and distribution of contrast agent-induced T and changes observed across multiple glioblastomas, the DRO's input parameters were trained using DSC-MRI data from 23 glioblastomas (>40 000 voxels).

Improving Primary Care Provider Practices in Youth Concussion Management.

Primary care providers are increasingly providing youth concussion care but report insufficient time and training, limiting adoption of best practices. We implemented a primary care-based intervention including an electronic health record-based clinical decision support tool ("SmartSet") and in-person training. We evaluated consequent improvement in 2 key concussion management practices: (1) performance of a vestibular oculomotor examination and (2) discussion of return-to-learn/return-to-play (RTL/RTP) guidelines.

Laser-Etched Designs for Molding Hydrogel-Based Engineered Tissues.

Rapid prototyping and fabrication of elastomeric molds for sterile culture of engineered tissues allow for the development of tissue geometries that can be tailored to different in vitro applications and customized as implantable scaffolds for regenerative medicine. Commercially available molds offer minimal capabilities for adaptation to unique conditions or applications versus those for which they are specifically designed. Here we describe a replica molding method for the design and fabrication of poly(dimethylsiloxane) (PDMS) molds from laser-etched acrylic negative masters with ∼0.

Pseudoprogression, radionecrosis, inflammation or true tumor progression? challenges associated with glioblastoma response assessment in an evolving therapeutic landscape.

The wide variety of treatment options that exist for glioblastoma, including surgery, ionizing radiation, anti-neoplastic chemotherapies, anti-angiogenic therapies, and active or passive immunotherapies, all may alter aspects of vascular permeability within the tumor and/or normal parenchyma. These alterations manifest as changes in the degree of contrast enhancement or T2-weighted signal hyperintensity on standard anatomic MRI scans, posing a potential challenge for accurate radiographic response assessment for identifying anti-tumor effects. The current review highlights the challenges that remain in differentiating true disease progression from changes due to radiation therapy, including pseudoprogression and radionecrosis, as well as immune or inflammatory changes that may occur as either an undesired result of cytotoxic therapy or as a desired consequence of immunotherapies.

Cigarette smoking and cardio-renal events in patients with atherosclerotic renal artery stenosis.

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population.

In vitro models of the cardiac microenvironment to study myocyte and non-myocyte crosstalk: bioinspired approaches beyond the polystyrene dish.

The heart is a complex pluricellular organ composed of cardiomyocytes and non-myocytes including fibroblasts, endothelial cells and immune cells. Myocytes are responsible for electrical conduction and contractile force generation, while the other cell types are responsible for matrix deposition, vascularization, and injury response. Myocytes and non-myocytes are known to communicate and exert mutual regulatory effects.

Effects of MRI Protocol Parameters, Preload Injection Dose, Fractionation Strategies, and Leakage Correction Algorithms on the Fidelity of Dynamic-Susceptibility Contrast MRI Estimates of Relative Cerebral Blood Volume in Gliomas.

Background And Purpose: DSC perfusion MR imaging assumes that the contrast agent remains intravascular; thus, disruptions in the blood-brain barrier common in brain tumors can lead to errors in the estimation of relative CBV. Acquisition strategies, including the choice of flip angle, TE, TR, and preload dose and incubation time, along with post hoc leakage-correction algorithms, have been proposed as means for combating these leakage effects. In the current study, we used DSC-MR imaging simulations to examine the influence of these various acquisition parameters and leakage-correction strategies on the faithful estimation of CBV.

Assessment of Cognitive and Neurologic Recovery in Ischemic Stroke Drug Trials: Results from a Randomized, Double-blind, Placebo-controlled Study.

Ischemic stroke is a serious medical condition with limited therapeutic options. The evaluation of the therapeutic potential of novel pharmacological interventions is carried-out in Phase II trials. The study design, primarily intended to evaluate efficacy and safety, is a balance between utilizing as few patients as possible to minimize safety risk and enrolling sufficient patients to detect unambiguous efficacy signals.