Comparing Deposition Characteristics of Various Embolic Particles Using an In Vitro Prostate Microvasculature Model.

Purpose: To compare spatial distributions of radiopaque glass (RG) microspheres, tris-acryl gelatin (TAG) microspheres, and polyvinyl alcohol (PVA) nonspherical foam particles within a planar in vitro microvascular model of the hyperplastic hemiprostate.

Materials And Methods: A microvascular model simulating hyperplastic hemiprostate was perfused with a water-glycerin mixture. A microcatheter was positioned distal to the model's prostatic artery origin, and embolic particles (RG, 50 μm, 100 μm, and 150 μm; TAG, 100-300 μm and 300-500 μm; and PVA, 90-180 μm and 180-300 μm) were administered using a syringe pump.

Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial.

Purpose: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial.

Materials And Methods: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S.

Unconventional mechanism of action and resistance to rapalogs in renal cancer.

mTORC1 is aberrantly activated in renal cell carcinoma (RCC) and is targeted by rapalogs. As for other targeted therapies, rapalogs clinical utility is limited by the development of resistance. Resistance often results from target mutation, but mTOR mutations are rarely found in RCC.

Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase.

WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214.

Y Contamination in the Interventional Radiology Suite: VARSKIN Estimation of Skin and Eye Injury and Review of Mitigation Strategies.

Our objective was to demonstrate, through computer simulations, radiation exposure levels from a Y contamination event during radioembolization procedures to calculate the radiation doses from various contamination scenarios. We also provide reasonable safety protocols to prevent contamination and minimize radiation exposure during decontamination. Simulations were performed using the computer code VARSKIN+, version 1.

Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada.

Background: Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking.

Slow breathing for reducing stress: The effect of extending exhale.

Introduction: Slow breathing techniques are commonly used to reduce stress. While it is believed by mind-body practitioners that extending the exhale time relative to inhale increases relaxation, this has not been demonstrated.

Methods: We conducted a 12-week randomized, single-blinded trial among 100 participants to compare if yoga-based slow breathing with an exhale greater inhale versus an exhale equals inhale produces measurable differences in physiological and psychological stress among healthy adults.

Comparison of Bolus Versus Dual-Syringe Administration Systems on Glass Yttrium-90 Microsphere Deposition in an In Vitro Microvascular Hepatic Tumor Model.

Purpose: To utilize an in vitro microvascular hepatic tumor model to compare the deposition characteristics of glass yttrium-90 microspheres using the dual-syringe (DS) and traditional bolus administration methods.

Materials And Methods: The microvascular tumor model represented a 3.5-cm tumor in a 1,400-cm liver with a total hepatic flow of 160 mL/min and was dynamically perfused.

Precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model.

Purpose: To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry.

Materials And Methods: A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.

Post-administration dosimetry in yttrium-90 radioembolization through micro-CT imaging of radiopaque microspheres in a porcine renal model.

The purpose of this study is to perform post-administration dosimetry in yttrium-90 radioembolization through micro-CT imaging of radiopaque microsphere distributions in a porcine renal model and explore the impact of spatial resolution of an imaging system on the extraction of specific dose metrics. Following the administration of radiopaque microspheres to the kidney of a hybrid farm pig, the kidney was explanted and imaged with micro-CT. To produce an activity distribution, 400 MBq of yttrium-90 activity was distributed throughout segmented voxels of the embolized vasculature based on an established linear relationship between microsphere concentration and CT voxel value.

Assessment of dynamic cardiac repolarization and contractility in patients with hypertrophic cardiomyopathy.

Aims: Arrhythmia mechanisms in hypertrophic cardiomyopathy remain uncertain. Preclinical models suggest hypertrophic cardiomyopathy-linked mutations perturb sarcomere length-dependent activation, alter cardiac repolarization in rate-dependent fashion and potentiate triggered electrical activity. This study was designed to assess rate-dependence of clinical surrogates of contractility and repolarization in humans with hypertrophic cardiomyopathy.

Direct control of CAR T cells through small molecule-regulated antibodies.

Antibody-based therapeutics have experienced a rapid growth in recent years and are now utilized in various modalities spanning from conventional antibodies, antibody-drug conjugates, bispecific antibodies to chimeric antigen receptor (CAR) T cells. Many next generation antibody therapeutics achieve enhanced potency but often increase the risk of adverse events. Antibody scaffolds capable of exhibiting inducible affinities could reduce the risk of adverse events by enabling a transient suspension of antibody activity.

Sustained mTORC1 activity during palbociclib-induced growth arrest triggers senescence in ER+ breast cancer cells.

Palbociclib, a selective CDK4/6 kinase inhibitor, is approved in combination with endocrine therapies for the treatment of advanced estrogen receptor positive (ER+) breast cancer. In pre-clinical cancer models, CDK4/6 inhibitors act primarily as cytostatic agents. In two commonly studied ER+ breast cancer cell lines (MCF7 and T47D), CDK4/6 inhibition drives G1-phase arrest and the acquisition of a senescent-like phenotype, both of which are reversible upon palbociclib withdrawal (incomplete senescence).

Anti-tumor immunity influences cancer cell reliance upon ATG7.

Macroautophagy (autophagy) is an essential cellular catabolic process required for survival under conditions of starvation. The role of autophagy in cancer is complex, context-dependent and at times contradictory, as it has been shown to inhibit, promote or be dispensable for tumor progression. In this study, we evaluated the contribution of the immune system to the reliance of tumors on autophagy by depleting autophagy-related 7 (ATG7) in murine tumor cells and grafting into immunocompetent versus immunodeficient hosts.

Premature battery depletion due to compromised low-voltage capacitor in a family of defibrillators.

Background: Boston Scientific (Marlborough, MA, USA) implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds) manufactured between 2008 and 2014 are potentially subject to premature battery depletion through a low-voltage capacitor malfunction occurring as a result of hydrogen buildup within the device. Although some of these devices are currently under advisory, other devices manufactured during this timeframe carry a lower risk of the same malfunction. These same devices are known to have superior longevity in general, and the overall mean lifespan of the devices remains long.

Cystine-glutamate antiporter xCT deficiency suppresses tumor growth while preserving antitumor immunity.

T cell-invigorating cancer immunotherapies have near-curative potential. However, their clinical benefit is currently limited, as only a fraction of patients respond, suggesting that these regimens may benefit from combination with tumor-targeting treatments. As oncogenic progression is accompanied by alterations in metabolic pathways, tumors often become heavily reliant on antioxidant machinery and may be susceptible to increases in oxidative stress.

Signal-averaged P wave area increases during respiratory events in patients with paroxysmal atrial fibrillation and obstructive sleep apnea.

Purpose: P wave characteristics change during simulated apneic events in individuals with atrial fibrillation (AF). This study sought to assess whether similar changes occur during nocturnal respiratory events in patients with AF and obstructive sleep apnea (OSA).

Methods: Thirty-five individuals with severe OSA who underwent formal polysomnography and subsequent AF ablation were compared to a matched group without AF.

Improvement in Sleep-Disordered Breathing Indices Downloaded From a Positive Airway Pressure Machine Following Conversion of Atrial Fibrillation to Sinus Rhythm.

Sleep-disordered breathing (SDB) is a contributor to atrial fibrillation (AF) and treatment of obstructive sleep apnea can reduce the recurrence of AF following catheter ablation. However, the effect of AF therapies on measures of SDB severity is less robustly described. We present the case of a middle-aged man with SDB and persistent AF who exhibited improvement in SDB metrics, as characterized by data downloaded from his auto-titrating continuous positive airway pressure (AutoCPAP) machine, very shortly following procedures that restored sinus rhythm.

A Case of Persistent Right Ventricular Failure after Rapid Decompression of a Large Chronic Pericardial Effusion.

• The authors report on PDS after pericardial drainage. • PDS is rare and can manifest as LV, biventricular, or RV failure. • Treatment is supportive, and recovery of ventricular function is expected in survivors.