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"Day, John D."
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Maturation of the internal auditory canal and posterior petrous bone with relevance to lateral and posterolateral skull base approaches
Anatomic knowledge of the internal auditory canal (IAC) and surrounding structures is a prerequisite for performing skull base approaches to the IAC. We herein perform a morphometric analysis of the IAC and surgically relevant aspects of the posterior petrous bone during pediatric maturation, a region well-studied in adults but not children. Measurements of IAC length (IAC-L), porus (IAC-D) and midpoint (IAC-DM) diameter, and distance from the porus to the common crus (CC; P-CC) and posterior petrosal surface (PPS) to the posterior semicircular canal (PSC; PPS-PSC) were made on thin-cut axial CT scans from 60 patients (grouped by ages 0–3, 4–7, 8–11 12–15, 16–18, and > 18 years). IAC-L increased 27.5% from 8.7 ± 1.1 at age 0–3 to 11.1 ± 1.1 mm at adulthood (p = 0.001), with the majority of growth occurring by ages 8–11. IAC-D (p = 0.52) and IAC-DM (p = 0.167) did not significantly change from ages 0–3 to adult. P-CC increased 31.1% from 7.7 ± 1.5 at age 0–3 to 10.1 ± 1.5 mm at adulthood (p = 0.019). PPS-PSC increased 160% from 1.5 ± 0.7 at age 0–3 to 3.9 ± 1.2 mm at adulthood (p < 0.001). The majority of growth in P-CC and PPS-PSC occurred by ages 12–15. Knowledge of these patterns may facilitate safe exposure of the IAC in children.
Journal Article
Atrial cardiomyopathy: from cell to bedside
Atrial cardiomyopathy refers to structural and electrical remodelling of the atria, which can lead to impaired mechanical function. While historical studies have implicated atrial fibrillation as the leading cause of cardioembolic stroke, atrial cardiomyopathy may be an important, underestimated contributor. To date, the relationship between atrial cardiomyopathy, atrial fibrillation, and cardioembolic stroke remains obscure. This review summarizes the pathogenesis of atrial cardiomyopathy, with a special focus on neurohormonal and inflammatory mechanisms, as well as the role of adipose tissue, especially epicardial fat in atrial remodelling. It reviews the current evidence implicating atrial cardiomyopathy as a cause of embolic stroke, with atrial fibrillation as a lagging marker of an increased thrombogenic atrial substrate. Finally, it discusses the potential of antithrombotic therapy in embolic stroke with undetermined source and appraises the available diagnostic techniques for atrial cardiomyopathy, including imaging techniques such as echocardiography, computed tomography, and magnetic resonance imaging as well as electroanatomic mapping, electrocardiogram, biomarkers, and genetic testing. More prospective studies are needed to define the relationship between atrial cardiomyopathy, atrial fibrillation, and embolic stroke and to establish a prompt diagnosis and specific treatment strategies in these patients with atrial cardiomyopathy for the secondary and even primary prevention of embolic stroke.
Journal Article
The Thing. Project Pegasus
\"Project Pegasus hired the blue-eyed Thing as its security guard - but what's the point if the base is already filled with super villains? It's the classic saga, featuring all yoru favorites - including Hercules and Thundra, Deathlok and Doctor Strange, Captain America and Marvel, Man-Thing and ... Classic Thing? Watch as bashful Benjy faces action in Olympus and the Nexus, and from Hollywood to Yancy Street! Gasp as three heroes debut new identities and thrill to all the fun of super heroes poler night! Plus: will lending a hand protecting the facility from the Lava Men earn Spider-Man a spot on the Avengers? Or will a super villain riot lead to pandemonium at Project Pegasus?\"--Page 4 of cover.
Book
A novel Cas9-targeted long-read assay for simultaneous detection of IDH1/2 mutations and clinically relevant MGMT methylation in fresh biopsies of diffuse glioma
Molecular biomarkers provide both diagnostic and prognostic results for patients with diffuse glioma, the most common primary brain tumor in adults. Here, we used a long-read nanopore-based sequencing technique to simultaneously assess
IDH
mutation status and
MGMT
methylation level in 4 human cell lines and 8 fresh human brain tumor biopsies. Currently, these biomarkers are assayed separately, and results can take days to weeks. We demonstrated the use of nanopore Cas9-targeted sequencing (nCATS) to identify
IDH1
and
IDH2
mutations within 36 h and compared this approach against currently used clinical methods. nCATS was also able to simultaneously provide high-resolution evaluation of
MGMT
methylation levels not only at the promoter region, as with currently used methods, but also at CpGs across the proximal promoter region, the entirety of exon 1, and a portion of intron 1. We compared the methylation levels of all CpGs to
MGMT
expression in all cell lines and tumors and observed a positive correlation between intron 1 methylation and
MGMT
expression. Finally, we identified single nucleotide variants in 3 target loci. This pilot study demonstrates the feasibility of using nCATS as a clinical tool for cancer precision medicine.
Journal Article
Guardians of the galaxy : tomorrow's heroes omnibus
\"A thousand years from now, Vance Astro, Yondu, Martinex and Charlie-27 will rise to free the enslaved planet Earth -- as the Guardians of the Galaxy! Soon, Captain America, Doctor Strange, the Thing, the Hulk and more join the time-spanning heroes in the war to reclaim the future! Threats arise from other worlds -- as well as new allies Nikki and the uncanny Starhawk! But when Guardians and Avengers join forces in the present day, will even the combined might of two millennia be enough to stop the deranged demigod Michael Korvac? Plus: the Silver Surfer, Ms. Marvel, Spider-Man and Adam Warlock!\"-- Amazon.com description.
Book
The Impact of Gender on Atrial Fibrillation Incidence and Progression to Dementia
There are a paucity of data regarding the role of gender and atrial fibrillation (AF) on cognitive decline and incidence of dementia. Such data may provide insight into the disproportionate incidence of dementia in women and may help identify high-risk characteristics to target for prevention. We examined patients who underwent coronary angiography at an Intermountain Healthcare Medical Center and enrolled in a prospective cardiovascular database. To be included, patients could not have a previous diagnosis of AF or dementia and had to have 5years of follow-up. Endpoints included incident AF and dementia. Study cohort consisted of 35,608 patients without a previous history of AF or dementia, with 14,377 (40.4%) being woman. Women had lower rates of hypertension, diabetes, coronary artery disease, and prior myocardial infarction, but higher rates of prior stroke. Men had a higher incidence of 5-year and long-term AF. However, women trended toward a higher incidence of 5-year and long-term dementia and stroke compared with men. In all groups of patients with and without AF, prior stroke predicted cognitive decline. In patients without a history of or development of AF, diabetes significantly increased risk of dementia. Women have higher rates of dementia over time than men, driven by higher baseline stroke rates and nontraditional cardiovascular risk factors. The higher dementia rates were in the setting of lower AF rates. However, in both men and women who develop AF, dementia rates are increased and do not show gender-based differences in risk.
Journal Article
Cardiovascular disease during the COVID-19 pandemic: Think ahead, protect hearts, reduce mortality
Coronavirus disease 2019 (COVID-19) is rapidly spreading globally. As of October 3, 2020, the number of confirmed cases has been nearly 34 million with more than 1 million fatalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for COVID-19. Newly diagnosed and worsening cardiovascular disease are common complications in COVID-19 patients, including acute cardiac injury, hypertension, arrhythmia, myocardial infarction, heart failure and sudden cardiac arrest. The mechanisms contributing to cardiac disease burden include hypoxemia, inflammatory factor storm, dysfunctional angiotensin converting enzyme 2 (ACE2), and drug-induced cardiac toxicity. Notably, the macrophages expressing ACE2 as direct host cells of SARS-CoV-2 secrete chemokine and inflammatory cytokines, as well as a decrease in cellular immune responses to SARS-CoV-2 infection due to elevated exhaustion levels and dysfunctional diversity of T cells, that may be accountable for the \"hyperinflammation and cytokine storm syndrome\" and subsequently acute cardiac injury and deteriorating cardiovascular disease in COVID-19 patients. However, no targeted medication or vaccines for COVID-19 are yet available. The management of cardiovascular disease in patients with COVID-19 include general supportive treatment, circulatory support, other symptomatic treatment, psychological assistance as well as online consultation. Further work should be concentrated on better understanding the pathogenesis of COVID-19 and accelerating the development of drugs and vaccines to reduce the cardiac disease burden and promote the management of COVID-19 patients, especially those with a severe disease course and cardiovascular complications.
Journal Article
The Population-Based Long-Term Impact of Anticoagulant and Antiplatelet Therapies in Low-Risk Patients With Atrial Fibrillation
Among patients with atrial fibrillation (AF), the risk of stroke risk is a significant concern. CHADS2 and CHA2DS2-VASc ≤2 scoring have been used to stratify patients into categories of risk. Without randomized, prospective data, the need and type of long-term antithrombotic medications for thromboembolism prevention in lower risk AF patients remains controversial. We sought to define the long-term impact of anticoagulant and antiplatelet therapy use in AF patients at low risk of stroke. A total of 56,764 patients diagnosed with AF and a CHADS2 score of 0 or 1, or CHA2DS2-VASc score of 0, 1, or 2 were studied. Antithrombotic therapy was defined as aspirin, clopidogrel (antiplatelet therapy), or warfarin monotherapy (anticoagulation) initiated within 6 months of AF diagnosis. End points included all-cause mortality, cerebrovascular accident, transient ischemic attack (TIA), and major bleed. The average age of the population was 67.0 ± 14.1 years and 56.6% were male. In total, 9,682 received aspirin, 1,802 received clopidogrel, 1,164 received warfarin, and 46,042 did not receive any antithrombotic therapy. Event rates differed between patients with a CHADS2 score of 0 and 1; 18.5% and 37.8% had died, 1.7% and 3.4% had a stroke, 2.2% and 3.2% had a TIA, and 14% and 12.5% had a major bleed, respectively (p <0.0001 for all). The rates of stroke, TIA, and major bleeding increased as antithrombotic therapy intensity increased from no therapy, to aspirin, to clopidogrel, and to warfarin (all p <0.0001). Similar outcomes were observed in low-risk CHA2DS2-VASc scores (0 to 2). In low-risk AF patients with a CHADS2 score of 0 to 1 or CHA2DS2-VASc score of 0 to 2, the use of aspirin, clopidogrel, and warfarin was not associated with lower stroke rates at 5 years compared with no therapy. However, the use of antithrombotic agents was associated with a significant risk of bleed.
Journal Article