Purpose of review
Determining the etiology of ischemic stroke is critical to administering targeted therapy to prevent recurrent stroke and further neurologic deterioration. Ischemic strokes of ...cardioembolic and cryptogenic etiologies are frequent and are often ultimately attributed to atrial fibrillation (AF). However, the paroxysmal nature of AF presents challenges for accurate and timely detection to prevent a recurrent stroke. The purpose of this review is to evaluate serologic, electrographic, echocardiographic, and radiologic markers of AF after an ischemic stroke.
Recent findings
Innovative applications of biotechnologies such as RNA gene expression profiling are being studied to characterize stroke etiology. Extended cardiac rhythm monitoring by implantable and wearable devices allows longer periods to capture paroxysmal AF. Echocardiographic measures including left atrial volume and parameters of left atrial strain increase the probability of detecting AF. Existing radiographic modalities are being investigated in novel ways to assess left atrial abnormalities associated with paroxysmal AF.
Summary
Emerging technologies and novel applications of existing methods are improving AF diagnostics in cryptogenic stroke patients with a high pre-test probability of this etiology. Future research will continue to optimize AF diagnosis after a cryptogenic ischemic stroke to inform clinical practice and prevent recurrent strokes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ObjectivesTo describe the experiences of patients who have postacute sequelae SARS-CoV-2 infection with internal vibrations and tremors as a prominent component, we leveraged the efforts by Survivor ...Corps, a grassroots COVID-19 patient advocacy group, to gather information from individuals belonging to its Facebook group with a history of COVID-19 suffering from vibrations and tremors.Setting and designA narrative analysis was performed on 140 emails and 450 social media comments from 140 individuals collected as a response to a call to >180 000 individuals participating in Survivor Corps between 15 July and 27 July 2021. We used common coding techniques and the constant comparative method for qualitative data synthesis and categorising emails. Coded data were entered into NVivo V.12 to identify recurrent themes, theme connections and supporting quotations. Comments were analysed using Word Clouds, generated with R V.4.0.3 using quanteda, wordcloud and tm packages.Main outcome measuresPatient-reported long COVID symptom themes and domains related to internal tremors and vibration.ResultsThe respondents’ emails represented 22 themes and 7 domains pertaining to their experience with internal tremor and vibrations. These domains were as follows: (1) symptom experience, description and anatomic location; (2) initial symptom onset; (3) symptom timing; (4) symptom triggers or alleviators; (5) change from baseline health status; (6) experience with medical establishment and (7) impact on individuals’ lives and livelihood. There were 22 themes in total, each corresponding to one of the broader domains. Among the responses, many described symptoms that varied in location, timing and triggers, occurred soon after their COVID-19 infection, and were markedly debilitating. There were often frustrating experiences with the healthcare system.ConclusionsThis study describes key themes and experiences among a group of people reporting long COVID and having a prolonged and debilitating symptom complex that prominently features internal tremors and vibrations.
Surfactant accumulates in alveolar macrophages of granulocyte-macrophage colony-stimulating factor (GM-CSF) knockout (KO) mice and pulmonary alveolar proteinosis (PAP) patients with a functional loss ...of GM-CSF resulting from neutralizing anti–GM-CSF antibody. Alveolar macrophages from PAP patients and GM-CSF KO mice are deficient in peroxisome proliferator-activated receptor-γ (PPARγ) and ATP-binding cassette (ABC) lipid transporter ABCG1. Previous studies have demonstrated that GM-CSF induces PPARγ. We therefore hypothesized that PPARγ promotes surfactant catabolism through regulation of ABCG1. To address this hypothesis, macrophage-specific PPARγ (MacPPARγ) knockout mice were utilized. MacPPARγ KO mice develop foamy, lipid-engorged Oil Red O positive alveolar macrophages. Lipid analyses revealed significant increases in the cholesterol and phospholipid contents of MacPPARγ KO alveolar macrophages and extracellular bronchoalveolar lavage (BAL)–derived fluids. MacPPARγ KO alveolar macrophages showed decreased expression of ABCG1 and a deficiency in ABCG1-mediated cholesterol efflux to HDL. Lipid metabolism may also be regulated by liver X receptor (LXR)–ABCA1 pathways. Interestingly, ABCA1 and LXRβ expression were elevated, indicating that this pathway is not sufficient to prevent surfactant accumulation in alveolar macrophages. These results suggest that PPARγ mediates a critical role in surfactant homeostasis through the regulation of ABCG1.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ...ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018.
This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge.
Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%;
, 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%,
<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 95% CI, 1.1-3.8) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis.
Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.
Objectives:
Our objective was to identify characteristics associated with having an acute ischemic stroke (AIS) among hospitalized COVID-19 patients and the subset of these patients with a neurologic ...symptom.
Materials and Methods:
Our derivation cohort consisted of COVID-19 patients admitted to Yale-New Haven Health between January 3, 2020 and August 28, 2020 with and without AIS. We also studied a sub-cohort of hospitalized COVID-19 patients demonstrating a neurologic symptom with and without an AIS. Demographic, clinical, and laboratory results were compared between AIS and non-AIS patients in the full COVID-19 cohort and in the sub-cohort of COVID-19 patients with a neurologic symptom. Multivariable logistic regression models were built to predict ischemic stroke risk in these two COVID-19 cohorts. These 2 models were externally validated in COVID-19 patients hospitalized at a major health system in New York. We then compared the distribution of the resulting predictors in a non-COVID ischemic stroke control cohort.
Results:
A total of 1,827 patients were included in the derivation cohort (AIS
N
= 44; no AIS
N
= 1,783). Among all hospitalized COVID-19 patients, history of prior stroke and platelet count ≥ 200 × 1,000/μL at hospital presentation were independent predictors of AIS (derivation AUC 0.89, validation AUC 0.82), irrespective of COVID-19 severity. Among hospitalized COVID-19 patients with a neurologic symptom (
N
= 827), the risk of AIS was significantly higher among patients with a history of prior stroke and age <60 (derivation AUC 0.83, validation AUC 0.81). Notably, in a non-COVID ischemic stroke control cohort (
N
= 168), AIS patients were significantly older and less likely to have had a prior stroke, demonstrating the uniqueness of AIS patients with COVID-19.
Conclusions:
Hospitalized COVID-19 patients who demonstrate a neurologic symptom and have either a history of prior stroke or are of younger age are at higher risk of ischemic stroke.
Pulmonary alveolar proteinosis (PAP) is a lung disease characterized by a deficiency of functional granulocyte macrophage colony-stimulating factor (GM-CSF) resulting in surfactant accumulation and ...lipid-engorged alveolar macrophages. GM-CSF is a positive regulator of PPARγ that is constitutively expressed in healthy alveolar macrophages. We previously reported decreased PPARγ and ATP-binding cassette transporter G1 (ABCG1) levels in alveolar macrophages from PAP patients and GM-CSF knockout (KO) mice, suggesting PPARγ and ABCG1 involvement in surfactant catabolism. Because ABCG1 represents a PPARγ target, we hypothesized that PPARγ restoration would increase ABCG1 and reduce macrophage lipid accumulation. Upregulation of PPARγ was achieved using a lentivirus expression system in vivo. GM-CSF KO mice received intratracheal instillation of lentivirus (lenti)-PPARγ or control lenti-eGFP. Ten days postinstillation, 79% of harvested alveolar macrophages expressed eGFP, demonstrating transduction. Alveolar macrophages showed increased PPARγ and ABCG1 expression after lenti-PPARγ instillation, whereas PPARγ and ABCG1 levels remained unchanged in lenti-eGFP controls. Alveolar macrophages from lenti-PPARγ-treated mice also exhibited reduced intracellular phospholipids and increased cholesterol efflux to HDL, an ABCG1-mediated pathway. In vivo instillation of lenti-PPARγ results in: 1) upregulating ABCG1 and PPARγ expression of GM-CSF KO alveolar macrophages, 2) reducing intracellular lipid accumulation, and 3) increasing cholesterol efflux activity.
This study is to compare socio-demographic, HIV testing, and prevention factors experienced by insured low-income heterosexual Black women and men.
We examined cross-sectional data from Black women ...and men (n = 5837) recruited in 23 U.S. cities for National HIV Behavioral Surveillance June-December 2019. We compared socio-demographic and behavioral factors between groups using log-linked Poisson regression models, producing adjusted prevalence ratios and 95% confidence intervals.
Black women were less likely than Black men to have private insurance (aPR 0.61, 95% CI 0.50-0.74, p < 0.0001). Black women were more likely than Black men to have incomes at or below the poverty line (aPR 1.04, 95% CI 1.01-1.07, p = 0.02), be aware of PrEP (aPR 1.20, 95% CI 1.12-1.28, p < 0.0001), and have been recently tested for HIV (aPR 1.12, 95% CI 1.04, 1.20, p < 0.01).
Despite insured status, many Black women and men experienced suboptimal access to and utilization of HIV testing and prevention services. Understanding how social conditions produce differential access to care may help inform HIV prevention interventions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Picking up a weekend food pack, or “Power Pack”, predicts lower food insecurity.•Program recipients who do not receive SNAP saw greater decreases in food insecurity.•Power Packs offers fresh foods, ...which promoted home cooking for non-SNAP families.•SNAP recipients were more likely to pick up packs at the end of their SNAP month.•Families who do and do not receive SNAP use local food assistance in different ways.
“Backpack” food programs administered through public schools are a potentially powerful additional source of nutrition for low-income students and their families. Typically, backpack programs send non-perishable foods home with children to supplement school meals. Power Packs Project (PPP) is a unique backpack program, in that it provides fresh food alongside accompanying recipes, with the explicit goals of not only reducing food insecurity but also facilitating home cooking and improving nutrition for the whole family. Using daily, repeated surveys sent via text-message to program parents (N = 178), this study is the first to examine the effect of picking up a Power Pack in a given week on parent and child food insecurity and meal routines. Additionally, it explores whether effects differed for families who also received federal food assistance through the Supplemental Nutrition Assistance Program (SNAP). Results indicate that Power Packs is associated with lower parent and child food insecurity; this relationship is even stronger among families who did not also receive SNAP. Power Packs also promotes home cooking, but only among families who did not receive SNAP. Analyses of program usage revealed that SNAP recipients were far more likely to pick up their packs at the end of their SNAP month than they were just after SNAP benefit distribution, suggesting they use the program to smooth food consumption in tandem with SNAP. Implications of these findings for food assistance programs and policies are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear transcription factor involved in lipid metabolism that is constitutively expressed in the alveolar macrophages of healthy ...individuals. PPARγ has recently been implicated in the catabolism of surfactant by alveolar macrophages, specifically the cholesterol component of surfactant while the mechanism remains unclear. Studies from other tissue macrophages have shown that PPARγ regulates cholesterol influx, efflux, and metabolism. PPARγ promotes cholesterol efflux through the liver X receptor-alpha (LXRα) and ATP-binding cassette G1 (ABCG1). We have recently shown that macrophage-specific PPARγ knockout (PPARγ KO) mice accumulate cholesterol-laden alveolar macrophages that exhibit decreased expression of LXRα and ABCG1 and reduced cholesterol efflux. We hypothesized that in addition to the dysregulation of these cholesterol efflux genes, the expression of genes involved in cholesterol synthesis and influx was also dysregulated and that replacement of PPARγ would restore regulation of these genes. To investigate this hypothesis, we have utilized a Lentivirus expression system (Lenti-PPARγ) to restore PPARγ expression in the alveolar macrophages of PPARγ KO mice. Our results show that the alveolar macrophages of PPARγ KO mice have decreased expression of key cholesterol synthesis genes and increased expression of cholesterol receptors CD36 and scavenger receptor A-I (SRA-I). The replacement of PPARγ (1) induced transcription of LXRα and ABCG1; (2) corrected suppressed expression of cholesterol synthesis genes; and (3) enhanced the expression of scavenger receptors CD36. These results suggest that PPARγ regulates cholesterol metabolism in alveolar macrophages.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The objective of this study was to examine the major constituent of nonesterified fatty acids in children with respect to auxologic parameters, insulin sensitivity, and lipid levels, because ...nonesterified fatty acid levels are elevated in obesity and are important in the development of comorbidities.
Fasting blood samples were obtained from 73 children (43 girls; 49 obese; median range age: 11.4 0.9-17.6 years). Concentrations of the major circulating nonesterified fatty acids (myristate, palmitate, oleate, stearate, and arachidate) were determined by gas chromatography mass spectrometry, alongside measurement of insulin, adiponectin, and lipid profiles.
The sum of all nonesterified fatty acids was significantly higher in obese versus normal-weight children, although gender (but not age or puberty) was an important determinant, with the difference remaining significant only in boys. Overall, obese children had higher concentrations of myristate, palmitate, and oleate but not stearate or arachidate. Age was an important determinant of myristate and arachidate, whereas gender proved more important for palmitate and stearate. Fasting insulin concentrations were not associated with either total nonesterified fatty acid concentrations or any of the individual nonesterified fatty acids, although a positive correlation was found between adiponectin and total nonesterified fatty acid concentrations that was independent of obesity status and that seemed mediated by changes in palmitate and stearate. Serum total cholesterol and low-density lipoprotein (but not high-density lipoprotein) levels seemed to correlate positively with circulating concentrations of palmitate, oleate, and stearate, whereas serum triacylglycerols correlated with myristate, palmitate, and oleate concentrations.
Nonesterified fatty acid concentrations are elevated in obese children, primarily as a result of increases in myristate, palmitate, and oleate. Independent effects of nonesterified fatty acids on circulating adiponectin levels and lipid parameters were observed, although we found no relationship between nonesterified fatty acid concentrations and the insulin resistance identified with obesity.
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