Fewer LAG-3+ T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.

The coinhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates T cell activation, proliferation, and homeostasis. Blockade or deletion of LAG-3 in autoimmune-prone backgrounds or induced-disease models has been shown to exacerbate disease. We observed significantly fewer LAG-3+ CD4 and CD8 T cells from subjects with relapsing-remitting multiple sclerosis (RRMS) and type 1 diabetes. Low LAG-3 protein expression was linked to alterations in mRNA expression and not cell surface cleavage. Functional studies inhibiting LAG-3 suggest that in subjects with RRMS, LAG-3 retains its ability to suppress T cell proliferation. However, LAG-3 expression was associated with the expression of markers of apoptosis, indicating a role for low LAG-3 in T cell resistance to cell death. In T cells from subjects with RRMS, we observed a global dysregulation of LAG-3 expression stemming from decreased transcription and persisting after T cell stimulation. These findings further support the potential clinical benefits of a LAG-3 agonist in the treatment of human autoimmunity.

Cutting Edge: Effect of Disease-Modifying Therapies on SARS-CoV-2 Vaccine-Induced Immune Responses in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS treated by diverse disease-modifying therapies that suppress the immune system. Severe acute respiratory syndrome coronavirus 2 mRNA vaccines have been very effective in immunocompetent individuals, but whether MS patients treated with modifying therapies are afforded the same protection is not known. This study determined that dimethyl fumarate caused a momentary reduction in anti-Spike (S)-specific Abs and CD8 T cell response. MS patients treated with B cell-depleting (anti-CD20) or sphingosine 1-phosphate receptor agonist (fingolimod) therapies lack significant S-specific Ab response. Whereas S-specific CD4 and CD8 T cell responses were largely compromised by fingolimod treatment, T cell responses were robustly generated in anti-CD20-treated MS patients, but with a reduced proportion of CD4+CXCR5+ circulating follicular Th cells. These data provide novel information regarding vaccine immune response in patients with autoimmunity useful to help improve vaccine effectiveness in these populations.

In ASCVD, 81 mg and 325 mg of aspirin did not differ for CV or bleeding events.

SOURCE CITATION: Jones WS, Mulder H, Wruck LM, et al. Comparative effectiveness of aspirin dosing in cardiovascular disease. N Engl J Med. 2021;384:1981-90. 33999548.

Comparison of parenteral treatments of acute primary headache in a large academic emergency department cohort.

OBJECTIVE: The objective of this article is to compare acute primary headache patient outcomes in those initially treated with parenteral opiates or non-opiate recommended headache medications in a large academic medical emergency department (ED). BACKGROUND: Many acute primary headache patients are not diagnosed with a specific headache type and are treated with opiates and nonspecific pain medications in the ED setting. This is inconsistent with multiple expert recommendations. METHODS: Electronic charts were reviewed from 574 consecutive patients who visited the ED for acute primary headache (identified by chief complaint and ICD9 codes) and were treated with parenteral medications. RESULTS: Non-opiate recommended headache medications were given first line to 52.6% and opiates to 22.8% of all participants. Patients given opiates first had significantly longer length of stays (median 5.0 vs. 3.9 hours, p < 0.001) and higher rates of return ED visits within seven days (7.6% vs. 3.0%, p = 0.033) compared with those given non-opiate recommended medications in univariate analysis. Only the association with longer length of stay remained significant in multivariable regression including possible confounding variables. CONCLUSIONS: Initial opiate use is associated with longer length of stay compared with non-opiate first-line recommended medications for acute primary headache in the ED. This association remained strong and significant even after multivariable adjustment for headache diagnosis and other possible confounders.

Quality of Neurologic Care in the United States: Initial Report From the Axon Registry.

OBJECTIVE: To provide the initial description of the quality of outpatient US neurologic care as collected and reported in the Axon Registry. METHODS: We describe characteristics of registry participants and the performance of neurology providers on 20 of the 2019 Axon Registry quality measures. From the distribution of providers' scores on a quality measure, we calculate the median performance for each quality measure. We test for associations between quality measure performance, provider characteristics, and intrinsic measure parameters. RESULTS: There were 948 neurology providers who contributed a total of 6,480 provider-metric observations. Overall, the average quality measure performance score at the provider level was 66 (median 77). At the measure level (n = 20), the average quality measure performance score was 53 (median 55) with a range of 2 to 100 (interquartile range 20-91). Measures with a lower-complexity category (e.g., discrete orders, singular concepts) or developed through the specialty's qualified clinical data registry pathway had higher performance distributions. There was no difference in performance between Merit-Based Incentive Payment System (MIPS) and non-MIPS providers. There was no association between quality measure performance and practice size, measure clinical topic/neurologic condition, or measure year of entry. CONCLUSIONS: This cross-sectional assessment of quality measure performance in 2019 Axon Registry data demonstrates modest performance scores and considerable variability across measures and providers. More complex measures were associated with lower performance. These findings serve as a baseline assessment of quality of ambulatory neurologic care in the United States and provide insights into future measure design.

Special requirements for electronic medical records in neurology.

Electronic medical records (EMRs) are being rapidly adapted in the United States with goals of improving patient care, increasing efficiency, and reducing costs. Neurologists must become knowledgeable about the utility and effectiveness of the important parts of these systems specifically needed for care of neurology patients. The field of neurology encompasses complex disorders whose diagnosis and management heavily relies on detailed medical documentation of history and physical examination, and often on specialty-specific ancillary tests and extensive neuroimaging. Small discrepancies in documentation or absence of an in-hand ancillary test result can drastically change the current workup or treatment decision of a complex patient with neurologic disease. We describe current models and opportunities for improvements to EMRs that provide utility and efficiency in the care of neurology patients.

Chronic pain and obesity in elderly people: results from the Einstein aging study.

OBJECTIVES: To determine the prevalence of chronic pain in elderly people and its relationship with obesity and associated comorbidities and risk factors. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: A representative community sample of 840 subjects aged 70 and older. MEASUREMENTS: The prevalence of chronic pain and its relationship with obesity (categories defined according to body mass index (BMI)), other medical risk factors, and psychiatric comorbidities were examined. Chronic pain was defined as pain of at least moderate severity (> or =4 on a 10-point scale) some, most, or all of the time for the previous 3 months. RESULTS: The sample was mostly female (62.8%), and the average age was 80 (range 70-101). The prevalence of chronic pain was 52% (39.7% in men; 58.9% in women). Subjects with chronic pain were more likely to report a diagnosis of depression (odds ratio (OR)=2.5, 95% confidence interval (CI)=1.40-4.55) and anxiety (OR=2.3, 95% CI=1.22-4.64). Obese subjects (BMI 30-34.9) were twice as likely (OR=2.1, 95%CI=1.33-3.28) and severely obese subjects (BMI> or =35) were more than four times as likely (OR=4.5, 95% CI=1.85-12.63) as those of normal weight (BMI 18.5-24.9) to have chronic pain. Obese subjects were significantly more likely to have chronic pain in the head, neck or shoulder, back, legs or feet, and abdomen or pelvis than subjects who were not obese. In multivariate models, obesity (OR=2.0, 95% CI=1.27-3.26) and severe obesity (OR=4.1, 95% CI=1.57-10.82) were associated with chronic pain after adjusting for age, sex, diabetes mellitus, hypertension, depression, anxiety, and education. CONCLUSION: Chronic pain is common in this elderly population, affects women more than men, and is highly associated with obesity.