SARS-CoV-2 remdesivir resistance mutations have been generated in vitro but have not been reported in patients receiving treatment with the antiviral agent. We present a case of an immunocompromised ...patient with acquired B-cell deficiency who developed an indolent, protracted course of SARS-CoV-2 infection. Remdesivir therapy alleviated symptoms and produced a transient virologic response, but her course was complicated by recrudescence of high-grade viral shedding. Whole genome sequencing identified a mutation, E802D, in the nsp12 RNA-dependent RNA polymerase, which was not present in pre-treatment specimens. In vitro experiments demonstrated that the mutation conferred a ~6-fold increase in remdesivir IC
but resulted in a fitness cost in the absence of remdesivir. Sustained clinical and virologic response was achieved after treatment with casirivimab-imdevimab. Although the fitness cost observed in vitro may limit the risk posed by E802D, this case illustrates the importance of monitoring for remdesivir resistance and the potential benefit of combinatorial therapies in immunocompromised patients with SARS-CoV-2 infection.
This observational study describes trends in emergency department visits and admission rates among US acute care hospitals using data from the National Emergency Department Survey.
Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers ...insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.
Guidelines recommend an inhaled corticosteroid (ICS) prescription on emergency department (ED) discharge after acute asthma exacerbations.
We sought to identify rates and predictors of ICS ...prescription at ED discharge. Secondary outcomes included ICS prescription rates in a high-risk subgroup, outpatient follow-up rates within 30 days, and variation in ICS prescriptions among attending emergency physicians.
This was a retrospective cohort study of adult asthma ED discharges for acute asthma exacerbation across 5 urban academic hospitals. We used multivariable logistic regression to evaluate predictors of ICS prescription after adjusting for patient characteristics and hospital-level clustering.
Among 3948 adult ED visits, an ICS was prescribed in 6% (n = 238) of visits. Only 14% (n = 552) completed an outpatient visit within 30 days. Among patients with 2 or more ED visits in 12 months, the ICS prescription rate was 6.7%. ICS administration in the ED (odds ratio OR 9.91; 95% CI 7.99–12.28) and prescribing a β-agonist on discharge (OR 2.67; 95% CI 2.08–3.44) were associated with higher odds of ICS prescription. Decreased odds of ICS prescription were associated with Hispanic ethnicity (OR 0.71; 95% CI 0.51–0.99) relative to Black race, and private (OR 0.75; 95% CI 0.62–0.91) or no insurance (OR 0.54; 95% CI 0.35–0.84) relative to Medicaid. One-third (36%, n = 66) of ED attendings prescribed 0 ICS prescriptions during the study period.
An ICS is infrequently prescribed on ED asthma discharge, and most patients do not have an outpatient follow-up within 30 days. Future studies should examine the extent to which ED ICS prescriptions improve outcomes for patients with barriers to accessing primary care.
Parkinson's disease (PD) is a progressively debilitating neurodegenerative syndrome. Although best described as a movement disorder, the condition has prominent autonomic, cognitive, psychiatric, ...sensory and sleep components. Striatal dopaminergic innervation and nigral neurons are progressively lost, with associated Lewy pathology readily apparent on autopsy. Nevertheless, knowledge of the molecular events leading to this pathophysiology is limited. Current therapies offer symptomatic benefit but they fail to slow progression and patients continue to deteriorate. Recent discoveries in sporadic, Mendelian and more complex forms of parkinsonism provide novel insight into disease etiology; 28 genes, including those encoding alpha-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2) and microtubule-associated protein tau (MAPT), have been linked and/or associated with PD. A consensus regarding the affected biological pathways and molecular processes has also started to emerge. In early-onset and more a typical PD, deficits in mitophagy pathways and lysosomal function appear to be prominent. By contrast, in more typical late-onset PD, chronic, albeit subtle, dysfunction in synaptic transmission, early endosomal trafficking and receptor recycling, as well as chaperone-mediated autophagy, provide a unifying synthesis of the molecular pathways involved. Disease-modification (neuroprotection) is no longer such an elusive goal given the unparalleled opportunity for diagnosis, translational neuroscience and therapeutic development provided by genetic discovery.
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