Trial of Antisense Oligonucleotide Tofersen for ALS.

Background: The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in ( ALS).

Methods: In this phase 3 trial, we randomly assigned adults with ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease.

Change in Physician Burnout between 2013 and 2020 in a Major Health System.

Objective: Assessing changes in physician burnout over time can offer insight into the causes of burnout. Existing studies are limited by using different samples of physicians at each time point. Our objective was to assess changes in burnout between 2013-2014 and 2019-2020 overall and within a cohort of physicians who took the survey twice.

Management of Refractory Status Epilepticus: An International Cohort Study (MORSE CODe) Analysis of Patients Managed in the ICU.

Background And Objectives: Status epilepticus that continues after the initial benzodiazepine and a second anticonvulsant medication is known as refractory status epilepticus (RSE). Management is highly variable because adequately powered clinical trials are missing. We aimed to determine whether propofol and midazolam were equally effective in controlling RSE in the intensive care unit, focusing on management in resource-limited settings.

Baseline predictors of in-hospital mortality after acute traumatic spinal cord injury: data from a level I trauma center.

Comorbidity scores are important predictors of in-hospital mortality after traumatic spinal cord injury (tSCI), but the impact of specific pre-existing diseases is unknown. This retrospective cohort study aims at identifying relevant comorbidities and explores the influence of end-of-life decisions. In-hospital mortality of all patients admitted to the study center after acute tSCI from 2011 to 2017 was assessed.

Alteration of circulating unconventional T cells in cerebral ischemia: an observational study.

Immune reactions provoked by cerebral ischemia play crucial roles in the pathogenesis of brain damage and contribute to tissue regeneration processes. While functions of many immune cell types in post-ischemic inflammation have been well studied in experimental stroke, the exact roles played by unconventional T cells in pathogenesis of the clinical stroke remain to be precisely determined. In the present study, we investigated the frequencies and absolute cell numbers of peripheral blood T lymphocyte subpopulations including those of invariant natural killer T (iNKT) cells, CD3CD56 NKT-like (NKTL) cells, and γδ T cells from patients with acute cerebral infarction (ACI), chronic cerebrovascular disease (CCD) or chronic cerebral circulation insufficiency (CCI) by flow cytometry, and analyzed their association with the disease severity and the clinical outcome.

One-year follow-up of disease burden and medication changes in patients with myasthenia gravis: From the MG Patient Registry.

Introduction/aims: We studied the progression of myasthenia gravis (MG) disease burden and medication adjustment among MG Patient Registry participants.

Methods: Participants diagnosed with MG (age ≥18 years), registered between July 1, 2013 and July 31, 2018 and completing both 6- and 12-month follow-up surveys, were included in this investigation. Participants were grouped into high-burden (Myasthenia Gravis Activity of Daily Living scale [MG-ADL] score ≥6) and low-burden (MG-ADL <6) groups based on MG-ADL scores at enrollment.

Spinal infection with intraspinal abscess or empyema and acute myelopathy: comparative analysis of diagnostics, therapy, complications and outcome in primary care.

Introduction: This study on pyogenic spinal infections with intraspinal epidural involvement (PSI +) compared the outcome of patients with spinal cord injury (SCI) to those without (noSCI) taking diagnostic algorithm, therapy, and complications into account.

Methods: Patients were enrolled in an ambispective study (2012-2017). Diagnostic and therapeutic algorithms, complications, and neurological outcome were analyzed descriptively.

Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Variant Carriers: the ATLAS Study.

Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology.

Bladder Management With Chronic Indwelling Catheter is Associated with Elevated Mortality in Patients with Spinal Cord Injury.

Objective: To evaluate the impact of bladder management method, specifically chronic indwelling catheter (IndC), on survival in patients with spinal cord injury (SCI) in Spinal Cord Injury Model System database.

Methods: Spinal Cord Injury Model System is a multicenter longitudinal database since 1970 with >40,000 patients with SCI. Adult patients (>18 at the time of injury) were screened.

Validation of myasthenia gravis diagnosis in the older Medicare population.

Introduction/aims: Administrative health data has been increasingly used to study the epidemiology of myasthenia gravis (MG) but a case ascertainment algorithm is lacking. We aimed to develop a valid algorithm for identifying MG patients in the older population with Medicare coverage.

Methods: Local older patients (age ≥65) who received healthcare at the Cleveland Clinic and possessed Medicare coverage in 2014 and 2015 were selected.

The importance of offering early genetic testing in everyone with amyotrophic lateral sclerosis.

Several genetically-targeted therapies are being developed for ALS. Research is increasingly supportive of a greater incidence of clinically actionable variants in sporadic ALS than previously reported. Salmon .

Improving Real-World Innovation and Problem Solving in Clinical Ethics: Insights from the First Clinical Ethics Un-Conference.

Despite an abundance of academic conferences, clinical ethicists lacked a forum to share innovative practices with peers and to generate solutions to common challenges. Organizers of the first Clinical Ethics Un-Conference developed a working event centered on active participation and problem solving through peer learning, with the goal of improving real-world practice. Registrants included 95 individuals from 64 institutions.

Notch signaling and natural killer cell infiltration in tumor tissues underlie medulloblastoma prognosis.

Medulloblastoma is the most common embryonic brain tumor in children. We investigated a cohort of 52 Asian medulloblastoma patients aged between 0 and 19 years old, who received surgical resections and post-resection treatments in the Taipei Medical University Hospital and the Taipei Veterans General Hospital. Genome-wide RNA sequencing was performed on fresh-frozen surgical tissues.

Multiple Sclerosis Wellness Shared Medical Appointment Model: A Pilot Study.

Background: Shared medical appointments (SMAs) are group medical visits combining medical care and patient education. We examined the impact of a wellness-focused pilot SMA in a large multiple sclerosis (MS) clinic.

Methods: We reviewed data on all patients who participated in the SMA from January 2016 through June 2019.

A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot-Marie-Tooth type 1A.

Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is a rare, orphan, hereditary neuromuscular disorder with no cure and for which only symptomatic treatment is currently available. A previous phase 2 trial has shown preliminary evidence of efficacy for PXT3003 in treating CMT1A. This phase 3, international, randomized, double-blind, placebo-controlled study further investigated the efficacy and safety of high- or low-dose PXT3003 (baclofen/naltrexone/D-sorbitol [mg]: 6/0.

Peripheral white blood cell responses as emerging biomarkers for patient stratification and prognosis in acute spinal cord injury.

Purpose Of Review: To date, prognostication of patients after acute traumatic spinal cord injury (SCI) mostly relies on the neurological assessment of residual function attributed to lesion characteristics. With emerging treatment candidates awaiting to be tested in early clinical trials, there is a need for wholistic high-yield prognostic biomarkers that integrate both neurogenic and nonneurogenic SCI pathophysiology as well as premorbid patient characteristics.

Recent Findings: It is becoming clearer that effective prognostication after acute SCI would benefit from integrating an assessment of pathophysiological changes on a systemic level, and with that, extend from a lesion-centric approach.

Gender differences in the risk of depressive disorders following the loss of a young child: a nationwide population-based longitudinal study.

Background: Losing a child to death is one of the most stressful life events experienced in adulthood. The aim of the current study is to investigate parental risk of seeking treatment for major depression disorders (MDD) after a child's death and to explore whether such connection may operate differentially by parents' prior medical condition.

Methods: We studied a retrospective cohort of 7245 parents (2987 mothers and 4258 fathers) identified in the National Health Insurance Research Database of Taiwan (NHIRD) who had lost a child with age between 1 and 12 years.

Prescription and acceptance of durable medical equipment in FORTITUDE-ALS, a study of in ALS: post hoc analyses of a randomized, double-blind, placebo-controlled clinical trial.

: To evaluate the possible effect of , a fast skeletal muscle troponin activator, on prescription and acceptance of durable medical equipment (DME) in the FORTITUDE-ALS trial. Health economic outcome information was collected in FORTITUDE-ALS (NCT03160898); sites recorded if and when DME, specifically manual or power wheelchairs, gastrostomy tubes, noninvasive ventilators, or augmentative language devices, was prescribed by a physician and accepted by the patient (DME-PAP) during the trial. Acceptance was defined as the patient agreeing the item was needed.