Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Prevalence of restless legs and association with patient-reported outcome measures in myasthenia gravis.

Study Objectives: Inflammatory and immune mechanisms are considered in restless legs syndrome (RLS) pathophysiology with several autoimmune diseases associated with RLS. There is a paucity of studies examining RLS prevalence in myasthenia gravis (MG), an autoimmune neuromuscular disease. This study investigated RLS prevalence and association with patient-reported measures in a large registry of participants with MG using a validated RLS diagnostic questionnaire.

RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study.

Background: This study was a randomised, double-blind, placebo-controlled study intended to establish the translatability of the RLS-0071 mechanisms of action from animal disease models to humans by inhibiting neutrophil-mediated inflammation at the tissue level and major inflammatory biomarkers. We hypothesised that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose lipopolysaccharide (LPS) in healthy participants.

Methods: Participants were randomised to one of three arms to receive inhaled LPS followed by three doses of either low-dose (10 mg·kg) or high-dose (120 mg·kg loading dose followed by two doses of 40 mg·kg) RLS-0071 or placebo (saline) every 8 h.

An exploration of the relationship between grit, reflection-in-learning, and academic performance in entry-level doctor of physical therapy students.

Introduction: Recent literature in physical therapy education suggests learners' non-cognitive skills, such as grit and reflection, may be predictors of success. Little is known about the relationship of these constructs to each other or success during the first year of entry level physical therapist education.

Objective: The purpose of this study was to assess the relationship between Reflection-In- Learning Scale (RLS), grit, and grade point average (GPA) of entry-level physical therapy students during the first year of didactic instruction.

A quantitative review of competing learning slope metrics: effects of age, sex, and clinical diagnosis.

Introduction: In learning and memory tests that involve multiple presentations of the same material, learning slope refers to the degree to which examinees improve performances over successive learning trials. We aimed to quantitatively review the traditional raw learning slope (RLS), and the newly created learning ratio (LR) to understand the effects of demographic variables and clinical diagnoses on learning slope (e.g.

Robot-Assisted Transcranial Doppler Versus Transthoracic Echocardiography for Right to Left Shunt Detection.

Background: Right to left shunt (RLS), including patent foramen ovale, is a recognized risk factor for stroke. RLS/patent foramen ovale diagnosis is made by transthoracic echocardiography (TTE), which is insensitive, transesophageal echocardiography, which is invasive, and transcranial Doppler (TCD), which is noninvasive and accurate but scarce.

Methods: We conducted a prospective, single-arm device clinical trial of robot-assisted TCD (raTCD) versus TTE for RLS diagnosis at 6 clinical sites in patients who presented with an event suspicious for embolic cerebrovascular ischemia from October 6, 2020 to October 20, 2021.

Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients.

Obesity dominates early effects on cardiac structure and arterial stiffness in people with type 2 diabetes.

Objective: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D.

Methods: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20).

The Targeted Agent and Profiling Utilization Registry Study: A pragmatic clinical trial.

The conceptual framework of pragmatism in clinical trials is explored using the American Society of Clinical Oncology's pragmatic, non-randomized, phase II, multi-center basket clinical trial, the Targeted Agent and Profiling Utilization Registry Study (NCT02693535) as a model. The Targeted Agent and Profiling Utilization Registry Study aims to identify signals of drug activity when Food and Drug Administration approved drugs are matched to pre-specified genomic targets in patients with advanced cancer outside of their approved indication(s). The objectives of the study are to generate evidence of potential signals of activity in targeted therapies prescribed in an off-label setting as well as to expose and educate community cancer centers to genomic testing and precision medicine through the study protocol.

Demographic and clinical risk factors for diagnosis of sleep disorders in ESRD patients.

Background: Sleep disturbances in patients with end-stage renal disease (ESRD) are common and more prevalent than in the general population. This study aims to assess the demographic and clinical risk factors for the diagnosis of sleep disorders in ESRD patients.

Methods: This study is a retrospective analysis of the United States Renal Data System (USRDS) to evaluate risk factors for the diagnosis of sleep disorders, including hypersomnolence, insomnia, restless leg syndrome (RLS), or obstructive or central sleep apnea (OSA/CSA).

Hypopituitarism After Mild Traumatic Brain Injury: A Case Report.

Hypopituitarism is characterized by an underactive pituitary gland and may result in growth hormone deficiency, hypothyroidism, testosterone deficiency, and/or adrenal insufficiency. Traumatic brain injury (TBI) exposure is a known risk factor for hypopituitarism. However, patients with hypopituitarism secondary to TBI exposure may go undiagnosed because the signs and symptoms of hypopituitarism can be subtle.

Right-to-Left Shunt in Divers with Neurological Decompression Sickness: A Systematic Review and Meta-Analysis.

Objective: The aim of this study was to assess the association between the presence of a right-to-left shunt (RLS) and neurological decompression sickness (NDCS) and asymptomatic brain lesions among otherwise healthy divers.

Background: Next to drowning, NDCS is the most severe phenotype of diving-related disease and may cause permanent damage to the brain and spinal cord. Several observational reports have described the presence of an RLS as a significant risk factor for neurological complications in divers, ranging from asymptomatic brain lesions to NDCS.

RLS-0071 Moderated Elevated Myeloperoxidase Level and Activity in an Asymptomatic Subject in Clinical Trial RLS-0071-101.

BACKGROUND RLS-0071 is a dual-targeting peptide developed for the regulation of humoral and cellular inflammation via inhibition of neutrophil effectors, including myeloperoxidase and neutrophil extracellular trap formation (NETosis). The safety, pharmacokinetics, and pharmacodynamics of single and multiple doses of RLS-0071 were evaluated in a first-in-human clinical trial in healthy volunteers. Myeloperoxidase is the major peroxidase enzyme present in neutrophilic granules and contributes to cellular inflammation.

Protocol for an evaluation of adherence monitoring and support interventions among people initiating antiretroviral therapy in Cape Town, South Africa-a multiphase optimization strategy (MOST) approach using a fractional factorial design.

Background: South Africa bears a large HIV burden with 7.8 million people with HIV (PWH). However, due to suboptimal antiretroviral therapy (ART) adherence and retention in care, only 66% of PWH in South Africa are virally suppressed.

Implementation Challenges for a Multisite Advance Care Planning Pragmatic Trial: Lessons Learned.

Background/problem: Advance care planning (ACP) pragmatic trials are needed.

Proposed Solution: We determined key system-level activities to implement ACP interventions for a cluster-randomized pragmatic trial. We identified patients with serious illness from 50 primary care clinics across three University of California health systems using a validated algorithm.

Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.

The genetic etiology of periodic limb movement in sleep.

Study Objectives: Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e.

Striatal mechanism of the restless legs syndrome.

Study Objectives: Brain iron deficiency has been reported to be associated with the restless legs syndrome (RLS). However, 30%-50% of RLS patients do not respond to iron therapy, indicating that mechanisms other than brain iron deficiency may also participate in this disease. The striatum is known to be involved in the modulation of motor activity.

Blood Biomarkers in Brain Injury Medicine.

Purpose Of Review: This review seeks to explore blood-based biomarkers with the potential for clinical implementation.

Recent Findings: Emerging non-proteomic biomarkers hold promise for more accurate diagnostic and prognostic capabilities, especially in the subacute to chronic phase of TBI recovery. Further, there is a growing understanding of the overlap between TBI-related and Dementia-related blood biomarkers.

The EPICC Family of Anti-Inflammatory Peptides: Next Generation Peptides, Additional Mechanisms of Action, and and Efficacy.

The EPICC peptides are a family of peptides that have been developed from the sequence of the capsid protein of human astrovirus type 1 and previously shown to inhibit the classical and lectin pathways of complement. The EPICC peptides have been further optimized to increase aqueous solubility and identify additional mechanisms of action. Our laboratory has developed the lead EPICC molecule, PA-dPEG24 (also known as RLS-0071), which is composed of a 15 amino acid peptide with a C-terminal monodisperse 24-mer PEGylated moiety.

Worsening Restless Leg Syndrome Symptoms as a Presentation of Colon Cancer: A Reminder to Work Up the Anemia.

Restless leg syndrome (RLS) is a common neurological disorder with an estimated prevalence of 10-35% in people over 65 years of age. Current clinical practice guidelines include the recommendation to check serum ferritin levels and provide iron supplementation if the ferritin level is ≤75 μg/L. We present a case of an 84-year-old man who developed worsening RLS symptoms over the past year despite up-titration of oral ropinirole to maximum daily dose.