Ophthalmic masquerades of the atherosclerotic carotids

Patients with carotid atherosclerosis can present with ophthalmic symptoms. These symptoms and signs can be due to retinal emboli, hypoperfusion of the retina and choroid, opening up of collateral channels, or chronic hypoperfusion of the globe (ocular ischemic syndrome). These pathological mechanisms can produce many interesting signs and a careful history can bring out important past symptoms pointing toward the carotid as the source of the patient''s presenting symptom. Such patients are at high risk for an ischemic stroke, especially in the subsequent few days following their first acute symptom. It is important for clinicians to be familiar with these ophthalmic symptoms and signs caused by carotid atherosclerosis for making an early diagnosis and to take appropriate measures to prevent a stroke. This review elaborates the clinical features, importance, and implications of various ophthalmic symptoms and signs resulting from atherosclerotic carotid artery disease.     

HCV Therapy: Treat now or wait?

The combination of first generation protease inhibitors, telaprevir or boceprevir with pegylated interferon and ribavirin has significantly improved response rates when compared to pegylated interferon and ribavirin alone. While safe and effective for many patients, the potential of current DAA based therapy has been limited by tolerability, especially in those with extensive co-morbidities. Newer therapies, likely with improved efficacy and safety profiles are under development, however the timing of availability of these agents remains speculative. The choice to treat with currently available therapy or to wait for newer therapy is complex. These decisions require understanding of unique patient characteristics as well as safety and efficacy of both available therapy and new therapies undergoing investigation.     

Marked bleeding diathesis in patients with platelet dysfunction due to a novel mutation in RASGRP2, encoding CalDAG-GEFI (p.Gly305Asp)

Congenital platelet function disorders are often the result of defects in critical signal transduction pathways required for platelet adhesion and clot formation. Mutations affecting RASGRP2, the gene encoding the Rap GTPase activator, CalDAG-GEFI, give rise to a novel, and rare, group of platelet signal transduction abnormalities. We here report platelet function studies for two brothers (P1 and P2) expressing a novel variant of RASGRP2, CalDAG-GEFI(p.Gly305Asp). P1 and P2 have a lifelong history of bleeding with severe epistaxis successfully treated with platelet transfusions or rFVIIa. Other bleedings include extended hemorrhage from minor wounds. Platelet counts and plasma coagulation were normal, as was αIIbβ3 and GPIb expression on the platelet surface. Aggregation of patients’ platelets was significantly impaired in response to select agonists including ADP, epinephrine, collagen, and calcium ionophore A23187. Integrin αIIbβ3 activation and granule release were also impaired. CalDAG-GEFI protein expression was markedly reduced but not absent. Homology modeling places the Gly305Asp substitution at the GEF-Rap1 interface, suggesting that the mutant protein has very limited catalytic activity. In summary, we here describe a novel mutation in RASGRP2 that affects both expression and function of CalDAG-GEFI and that causes impaired platelet adhesive function and significant bleeding in humans.     

Trautmann's triangle anatomy with application to posterior transpetrosal and other related skull base procedures

Trautmann's triangle (TT) faces the cerebellopontine angle and is exposed during posterior transpetrosal approaches. However, reports on the morphometric analysis of this structure are lacking in the literature. The goal was to better understand this important operative corridor. TT was exposed from an external approach (transmastoid) in ten cadavers (20 sides) and from an internal approach on 20 dry adult temporal bones. Measurements included calculation of the area of TT and the distance of the endolymphatic sac from the anterior border of the sigmoid sinus. The area range of TT was 45–210 mm² (mean 151 mm²; SD 37 mm²). Three types of triangles were identified based on area. Type I triangles had areas less than 75 mm², Type II areas were 75–149 mm², and Type III areas were 150 mm² and greater. These types were observed in 37.5%, 35%, and 27.5% of sides, respectively. The distance from the jugular bulb's anterior border to the posterior border of the posterior semicircular canal ranged from 6 to 11 mm (mean 8.5 mm). The endolymphatic sac was located in the inferior portion of TT and traveled anterior to the sigmoid sinus. The horizontal distance from the anterior edge of the sigmoid sinus to the posterior edge of the endolymphatic sac ranged from 0 to 13.5 mm (mean 9 mm). Additional anatomic knowledge regarding TT may improve neurosurgical procedures in this region by avoiding intrusion into the endolymphatic sac and sigmoid sinus. Clin. Anat. 27:994–998, 2014. © 2014 Wiley Periodicals, Inc.     

Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.     

Evidence-Based Strategies for Clinical Organizations to Address COVID-19 Vaccine Hesitancy

The success of vaccination programs is contingent upon irrefutable scientific safety data combined with high rates of public acceptance and population coverage. Vaccine hesitancy, characterized by lack of confidence in vaccination and/or complacency about vaccination that may lead to delay or refusal of vaccination despite the availability of services, threatens to undermine the success of coronavirus disease 2019 (COVID-19) vaccination programs. The rapid pace of vaccine development, misinformation in popular and social media, the polarized sociopolitical environment, and the inherent complexities of large-scale vaccination efforts may undermine vaccination confidence and increase complacency about COVID-19 vaccination. Although the experience of recent lethal surges of COVID-19 infections has underscored the value of COVID-19 vaccines, ensuring population uptake of COVID-19 vaccination will require application of multilevel, evidence-based strategies to influence behavior change and address vaccine hesitancy. Recent survey research evaluating public attitudes in the United States toward the COVID-19 vaccine reveals substantial vaccine hesitancy. Building upon efforts at the policy and community level to ensure population access to COVID-19 vaccination, a strong health care system response is critical to address vaccine hesitancy. Drawing on the evidence base in social, behavioral, communication, and implementation science, we review, summarize, and encourage use of interpersonal, individual-level, and organizational interventions within clinical organizations to address this critical gap and improve population adoption of COVID-19 vaccination.