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Exploring a Novel Outcome Measure of Symptom Progression in Knee Osteoarthritis Utilizing a Large Randomized Trial.
Osteoarthritis Cartilage
December 2024
Formation Bio, Inc., Research and Development, New York City, NY, USA; Caduceus Biomedical Consulting, LLC, Durham, NC, USA; Duke University School of Medicine, Department of Medicine, Division of Rheumatology, Durham, NC, USA.
Objectives: Explore a newly defined composite measure of symptom progression for knee osteoarthritis (KOA) in a large, randomized study of a potential disease-modifying osteoarthritis drug (DMOAD).
Design: Using longitudinal KOA studies, a potential composite endpoint of time to symptom progression was defined as the first occurrence of worsening of WOMAC Pain of ≥10 points with no improvement (≤9 point decrease) in WOMAC Function (0-100 scale). A post hoc analysis explored discrimination and association with structural outcomes in the sprifermin FORWARD trial through Years 3 and 5.
Impact of noradrenergic inhibition on neuroinflammation and pathophysiology in mouse models of Alzheimer's disease.
J Neuroinflammation
December 2024
Department of Neurosurgery, Stanford University School of Medicine, 1050 Arastradero Road, Building A, Palo Alto, Stanford, CA, 94304, United States of America.
Norepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty and stress, and it also regulates neuroinflammation. We previously demonstrated behavioral and immunomodulatory effects of beta-adrenergic pharmacology in mouse models of Alzheimer's disease (AD). The current studies were designed to block noradrenergic signaling in 5XFAD mice through (1) chemogenetic inhibition of the locus coeruleus (LC), (2) pharmacologic blocking of β-adrenergic receptors, and (3) conditional deletion of β1- or β2-adrenergic receptors (adrb1 or adrb2) in microglia.
View Article and Find Full Text PDFPerioperative Management of Takayasu Arteritis for Cardiac Surgery - Review and Single-Center Experience.
Circ J
November 2024
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute.
Article Synopsis
- - Takayasu arteritis (TAK) is a serious condition that affects large blood vessels, leading to issues like blockages and aneurysms; it's primarily treated with glucocorticoids, but new biological drugs like tocilizumab are proving effective.
- - Patients on tocilizumab may face higher surgical complications, such as infection or delayed healing, and typically do not show increased inflammatory markers during infections, making management challenging.
- - There is a lack of guidelines for the best perioperative care for TAK patients needing cardiovascular surgery, but this article proposes a protocol based on recent evidence to help reduce complications in these patients.
A Meta-Analysis Examining the Effect of Perioperative Biologic Disease-Modifying Anti-Rheumatic Medications on Postoperative Wound Complications in Various Orthopedic Surgeries.
J Clin Med
September 2024
Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni Suef 65211, Egypt.
This meta-analysis was designed to compare the risk of postoperative wound complications in various orthopedic surgeries (OSs) affected by the perioperative use of biologic disease-modifying anti-rheumatic drugs (bDMARDs). The odds ratio (OR) and mean difference (MD), with 95% confidence intervals (CIs), were calculated using dichotomous or continuous random or fixed-effect models, based on the meta-analysis data. This study incorporated 14 investigations conducted between 2005 and 2023, encompassing a total population of 19,021 individuals undergoing diverse OSs.
View Article and Find Full Text PDFDisease-modifying rdHSV-CA8* non-opioid analgesic gene therapy treats chronic osteoarthritis pain by activating Kv7 voltage-gated potassium channels.
Front Mol Neurosci
July 2024
Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, FL, United States.
Chronic pain is common in our population, and most of these patients are inadequately treated, making the development of safer analgesics a high priority. Knee osteoarthritis () is a primary cause of chronic pain and disability worldwide, and lower extremity OA is a major contributor to loss of quality-adjusted life-years. In this study we tested the hypothesis that a novel JDNI8 replication-defective herpes simplex-1 viral vector () incorporating a modified carbonic anhydrase-8 transgene () produces analgesia and treats monoiodoacetate-induced () chronic knee pain due to OA.
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