Comparative Cardiovascular Safety of Gonadotropin-releasing Hormone Antagonists and Agonists Among Patients Diagnosed with Prostate Cancer: A Systematic Review and Meta-analysis of Real-world Evidence Studies.

Background And Objective: Gonadotropin-releasing hormone (GnRH) antagonists and agonists are cornerstone treatments in prostate cancer. However, evidence regarding the comparative cardiovascular safety of these drugs from clinical trials is inconclusive. The objective of this study was to systematically assess the risk of adverse cardiovascular events of GnRH antagonists compared with GnRH agonists across real-world evidence studies.

Global epidemiology of cannabis use disorders and its trend from 1990 to 2019: Benchmarking analysis of the global burden of disease study.

Introduction: Cannabis is one of the most widely used psychoactive substances globally, with an increasing trend in its legalization for both medical and recreational purposes in various countries. While cannabis offers potential therapeutic benefits, its regular use can lead to the development of Cannabis Use Disorders (CUDs). Understanding the epidemiology of CUDs is crucial in assessing the public health burden associated with cannabis use.

Beyond the Rash: Exploring the Symptoms and Diagnosis of Dermatomyositis.

Dermatomyositis represents a rare autoimmune disorder characterized by the concurrent presentation of inflammatory myopathy and distinctive cutaneous manifestations. Herein, we present a comprehensive case report involving a 62-year-old male patient exhibiting a complex array of symptoms encompassing progressive muscle weakness, characteristic dermatological findings, and systemic involvement. This case report serves to illuminate the diagnostic intricacies inherent to dermatomyositis and underscore the imperative for a multidisciplinary approach to its effective management.

Bile acid-containing lipid nanoparticles enhance extrahepatic mRNA delivery.

Lipid nanoparticles (LNPs) have emerged as a viable, clinically-validated platform for the delivery of mRNA therapeutics. LNPs have been utilized as mRNA delivery systems for applications including vaccines, gene therapy, and cancer immunotherapy. However, LNPs, which are typically composed of ionizable lipids, cholesterol, helper lipids, and lipid-anchored polyethylene glycol, often traffic to the liver which limits the therapeutic potential of the platform.

In Vivo mRNA CAR T Cell Engineering via Targeted Ionizable Lipid Nanoparticles with Extrahepatic Tropism.

With six therapies approved by the Food and Drug Association, chimeric antigen receptor (CAR) T cells have reshaped cancer immunotherapy. However, these therapies rely on ex vivo viral transduction to induce permanent CAR expression in T cells, which contributes to high production costs and long-term side effects. Thus, this work aims to develop an in vivo CAR T cell engineering platform to streamline production while using mRNA to induce transient, tunable CAR expression.

Insulin concentrations following termination of high-dose insulin euglycemic therapy.

Introduction: High-dose insulin therapy is used in patients with calcium channel blocker and beta-adrenergic antagonist overdoses. The pharmacokinetics of insulin are scantly reported following high-dose insulin therapy. We present two cases of persistently elevated insulin concentrations following high-dose insulin therapy.

A 70-Year-Old Woman Presenting with Confusion and Muscle Spasms Due to Serotonin Syndrome Associated with Paroxetine and Quetiapine Treatment.

BACKGROUND Serotonin toxicity, often referred to as 'serotonin syndrome,' is a drug-induced condition due to excess serotonin released from brain synapses, resulting in symptoms that may be autonomic, neuromuscular, and/or cognitive in nature. Most cases involve more than 1 of the following drug regimens: monoamine oxidase inhibitors (MAOIs), serotonin releasers, selective serotonin reuptake inhibitors (SSRIs), or serotonin-norepinephrine reuptake inhibitors (SNRIs). This report is of a 70-year-old woman who presented with confusion and muscle spasms due to serotonin toxicity associated with paroxetine and quetiapine treatment.

INSPIRE: Safety and tolerability of inhaled Yutrepia (treprostinil) in pulmonary arterial hypertension (PAH).

The INSPIRE trial was a Phase 3, open-label, multicenter trial (LTI-301) that enrolled patients with pulmonary arterial hypertension (PAH) ≥ 18 years of age who transitioned to Yutrepia from nebulized treprostinil (Transition) or added Yutrepia to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The objectives of the trial were to evaluate the safety and tolerability of Yutrepia (dry-powder formulation of treprostinil) in patients with PAH. The primary safety measures were the incidence of adverse events (AEs) and serious AEs.

Hydroxycholesterol substitution in ionizable lipid nanoparticles for mRNA delivery to T cells.

Delivery of nucleic acids, such as mRNA, to immune cells has become a major focus in the past decade with ionizable lipid nanoparticles (LNPs) emerging as a clinically-validated delivery platform. LNPs-typically composed of ionizable lipids, cholesterol, phospholipids, and polyethylene glycol lipids -have been designed and optimized for a variety of applications including cancer therapies, vaccines, and gene editing. However, LNPs have only recently been investigated for delivery to T cells, which has various therapeutic applications including the engineering of T cell immunotherapies.

Amniotic fluid stabilized lipid nanoparticles for in utero intra-amniotic mRNA delivery.

Congenital disorders resulting in pathological protein deficiencies are most often treated postnatally with protein or enzyme replacement therapies. However, treatment of these disorders in utero before irreversible disease onset could significantly minimize disease burden, morbidity, and mortality. One possible strategy for the prenatal treatment of congenital disorders is in utero delivery of messenger RNA (mRNA).

Orthogonal Design of Experiments for Optimization of Lipid Nanoparticles for mRNA Engineering of CAR T Cells.

Viral engineered chimeric antigen receptor (CAR) T cell therapies are potent, targeted cancer immunotherapies, but their permanent CAR expression can lead to severe adverse effects. Nonviral messenger RNA (mRNA) CAR T cells are being explored to overcome these drawbacks, but electroporation, the most common T cell transfection method, is limited by cytotoxicity. As a potentially safer nonviral delivery strategy, here, sequential libraries of ionizable lipid nanoparticle (LNP) formulations with varied excipient compositions were screened in comparison to a standard formulation for improved mRNA delivery to T cells with low cytotoxicity, revealing B10 as the top formulation with a 3-fold increase in mRNA delivery.

Pernicious anaemia: cause of recurrent cerebral venous thrombosis.

This case of recurrent cerebral venous thrombosis (CVT) highlights hyperhomocysteinemia in pernicious anemia due to vitamin B deficiency. No other risk factors such as trauma, infections, coagulation disorders or autoimmune diseases were present. The patient was cured with vitamin B and anticoagulation therapy.

Evaluating Core Clerkships: Lessons Learned From Implementing a Student-Driven Feedback System for Clinical Curricula.

Problem: Medical schools have implemented various ways to engage students in improving medical curricula. These systems, however, usually focus on the preclerkship curriculum, perhaps because medical students move through this phase of medical education synchronously, making it easier to collect student input. In contrast, clerkship and postclerkship curricula often lack similar levels of student engagement in program evaluation.

Tibiofemoral Contact Mechanics With Horizontal Cleavage Tears and Treatment of the Lateral Meniscus in the Human Knee: An In Vitro Cadaver Study.

Background: Partial meniscectomy is one of the most commonly performed orthopaedic procedures for a meniscus tear. Decreased contact area and increased contact pressure have been seen in partial meniscectomies from treatment of various types of meniscal tears; however, the biomechanical effect of a horizontal cleavage tear in the lateral meniscus and subsequent treatment are unknown.

Questions/purposes: This study asked whether a horizontal cleavage tear of the lateral meniscus, resecting the inferior leaf, and further resecting the superior leaf would (1) decrease contact area and (2) increase peak contact pressure.

Arthroscopic Anterior Cruciate Ligament Femoral Tunnel Visualization for Button Fixation.

Arthroscopic reconstruction of the anterior cruciate ligament (ACL) remains one of the most commonly performed procedures in orthopaedic surgery. We describe a technique to visualize the button being advanced through the femoral tunnel using an arthroscope placed in the anteromedial portal. Looking into the femoral tunnel in line with the sutures, this technique allows the surgeon to directly visualize the femoral button as it traverses the femoral tunnel and confirms that it is engaged over the femoral cortex.

Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition.

Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI). At a cellular level, tight junction proteins (TJPs) between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1) that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1β (IL-1β) as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9) are key mediators of trauma-associated brain edema.

Effects of combination of aliskiren and pentoxyfylline on renal function in the rat remnant kidney model of chronic renal failure.

Objectives: The aim was to investigate the nephroprotective effect of combination of aliskiren (ASK), a direct renin inhibitor and pentoxifylline (PTX), inhibitor of tumor necrotic factor-alpha (TNF-alpha), in rat remnant kidney model of chronic kidney disease (CKD).

Materials And Methods: Nephrectomized (NPX) rats were treated with ASK (10 mg/kg, p.o.

Nine year follow-up of a ceramic-on-ceramic bearing total hip arthroplasty utilizing a layered monoblock acetabular component.

Introduction: Early ceramic bearing systems in total hip arthoplasty (THA) sought to provide long term wear improvement over traditional metal on polyethylene systems. However, previous designs exhibited fractures of the ceramic acetabular liner, leading to the development of the Implex Hedrocel ceramic bearing THA system where the ceramic liner was supported on a layer of polyethylene intended to transition liner loads to the metal shell, a so-called "sandwich" design. Unfortunately, the device trial was stopped to further enrollment when liner fractures were reported.

Angle stable nails provide improved healing for a complex fracture model in the femur.

Background: Conventional nails are being used for an expanding range of fractures from simple to more complex. Angle stable designs are a relatively new innovation; however, it is unknown if they will improve healing for complex fractures.

Questions/purposes: When comparing traditional and angle stable nails to treat complex open canine femur fractures, the current study addressed the following questions: do the two constructs differ in (1) radiographic evidence of bone union across the cortices; (2) stability as determined by toggle (torsional motion with little accompanying torque) and angular deformation; (3) biomechanical properties, including stiffness in bending, axial compression, and torsional loading, and construct failure properties in torsion; and (4) degree of bone tissue mineralization?

Methods: Ten hounds with a 1-cm femoral defect and periosteal stripping were treated with a reamed titanium angle stable or nonangle stable nail after the creation of a long soft tissue wound.