Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

Background And Objectives: Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

Methods: Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium).

Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury.

Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1. PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death.

Health Economic Evaluations of Hip and Knee Interventions in Orthopaedic Sports Medicine: A Systematic Review and Quality Assessment.

Background: The economic burden of musculoskeletal diseases is substantial and growing. Economic evaluations compare costs and health benefits of interventions simultaneously to help inform value-based care; thus, it is crucial to ensure that studies are using appropriate methodology to provide valid evidence on the cost-effectiveness of interventions. This is particularly the case in orthopaedic sports medicine, where several interventions of varying costs are available to treat common hip and knee conditions.

A Novel Endovascular Therapy for CSF Hypotension Secondary to CSF-Venous Fistulas.

We report a consecutive case series of patients who underwent transvenous embolization of the paraspinal vein, which was draining the CSF-venous fistula, for treatment of spontaneous intracranial hypotension. These are the first-ever reported cases of this treatment for CSF-venous fistulas. All patients underwent spinal venography following catheterization of the azygous vein and then selective catheterization of the paraspinal vein followed by embolization of the vein with Onyx.

Thromboprophylaxis with Rivaroxaban in Acutely Ill Medical Patients with Renal Impairment: Insights from the MAGELLAN and MARINER Trials.

Patients with renal impairment are at higher risk of thrombosis and bleeding than those with normal renal function. The optimal rivaroxaban dose for thromboprophylaxis in acutely ill medical patients with renal impairment is unknown. MARINER and MAGELLAN were multicenter, randomized clinical trials of rivaroxaban in acutely ill medical patients.

, a Novel Transcription Factor and a Coregulator of Nuclear Factor B p65: Single Nucleotide Polymorphism and Estrogen Dependence.

T-cell leukemia 1A () single-nucleotide polymorphisms (SNPs) have been associated with aromatase inhibitor-induced musculoskeletal adverse events. We previously demonstrated that TCL1A is inducible by estradiol (E) and plays a critical role in the regulation of cytokines, chemokines, and Toll-like receptors in a SNP genotype and estrogen-dependent fashion. Furthermore, SNP-dependent expression phenotypes can be "reversed" by exposure to selective estrogen receptor modulators such as 4-hydroxytamoxifen (4OH-TAM).

Single-Nucleotide Polymorphisms and Estrogen-Mediated Toll-Like Receptor-MYD88-Dependent Nuclear Factor-B Activation: Single-Nucleotide Polymorphism- and Selective Estrogen Receptor Modulator-Dependent Modification of Inflammation and Immune Response.

In a previous genome-wide association study (GWAS) for musculoskeletal adverse events during aromatase inhibitor therapy for breast cancer, we reported that single nucleotide polymorphisms (SNPs) near the gene were associated with this adverse drug reaction. Functional genomic studies showed that TCL1A expression was induced by estradiol, but only in cells with the variant sequence for the top GWAS SNP (rs11849538), a SNP that created a functional estrogen response element. In addition, genotype influenced the downstream expression of a series of cytokines and chemokines and had a striking effect on nuclear factor B (NF-B) transcriptional activity.

Estrogen, SNP-Dependent Chemokine Expression and Selective Estrogen Receptor Modulator Regulation.

We previously reported, on the basis of a genome-wide association study for aromatase inhibitor-induced musculoskeletal symptoms, that single-nucleotide polymorphisms (SNPs) near the T-cell leukemia/lymphoma 1A (TCL1A) gene were associated with aromatase inhibitor-induced musculoskeletal pain and with estradiol (E2)-induced TCL1A expression. Furthermore, variation in TCL1A expression influenced the downstream expression of proinflammatory cytokines and cytokine receptors. Specifically, the top hit genome-wide association study SNP, rs11849538, created a functional estrogen response element (ERE) that displayed estrogen receptor (ER) binding and increased E2 induction of TCL1A expression only for the variant SNP genotype.

Aromatase inhibitor-associated bone fractures: a case-cohort GWAS and functional genomics.

Bone fractures are a major consequence of osteoporosis. There is a direct relationship between serum estrogen concentrations and osteoporosis risk. Aromatase inhibitors (AIs) greatly decrease serum estrogen levels in postmenopausal women, and increased incidence of fractures is a side effect of AI therapy.

Developing a video-mediated communication system for hospitalized children.

When a student is away from school for an extended time due to illness, he/she is provided with a tutor or access to in-hospital classrooms to keep up with his/her studies. This isolates the child from normal classroom experiences. A remote-control videoconferencing system (VCS), P.