Faculty Bibliography

Objective/UNASSIGNED:To identify and compare patient and procedural variables that are associated with a high radiation dose exposure and worse clinical outcomes between transradial arterial (TRA) and transfemoral arterial (TFA) approaches. Design/UNASSIGNED:This was a retrospective analysis. Setting/UNASSIGNED:A community hospital during the initial phase of adopting a TRA-first approach. Participants/UNASSIGNED:A resultant 215 subjects who only underwent diagnostic cerebral angiograms (DCA) after excluding all therapeutic procedures and patients under 18 years. Interventions/UNASSIGNED:Only DCA from 1 May 2018 to 31 January 2021. Main outcome measures/UNASSIGNED:We compared radiation exposure parameters (total fluoroscopy time (FT), total radiation dose (TD) and dose area product (DAP), number of vessels injected and Patient-Reported Global Health Physical and Mental Outcome Scores (PROGHS) at 30 days postprocedure between groups. Results/UNASSIGNED:FT was significantly greater in TRA compared with TFA (p<0.001). In addition, TRA had a significantly higher TD (p=0.002) and DAP (p=0.005) when compared with TFA. Analysis of only 6-vessel DCAs also showed that TRA had a significantly higher FT, DAP and TD in comparison to TFA. Despite observing a longer FT in TRA, results showed fewer vessels injected and a notably lower success rate in acquiring a 6-vessel DCA using the TRA. Further analysis of the effect of vessel number on FT using general linear models showed that with every increase of one vessel, the FT increases by 2.2 min for TRA (p<0.001; 95% CI 1.03 to 3.36) and by 1.3 min for TFA (p<0.001; 95% CI 0.72 to 1.83). There was no significant difference between groups in PROGHS mental and physical t-scores at 30 days postprocedure, even though our cohort showed a significantly greater percentage of TRA procedures done in the outpatient setting. Conclusions/UNASSIGNED:Adopting a TRA first approach for DCAs may be initially associated with a higher radiation dose for the patient. Better strategies and devices are needed to mitigate this effect.

The utility of the Victoria Symptom Validity Test (VSVT) as a performance validity test (PVT) has been primarily established using response accuracy scores. However, the degree to which response latency may contribute to accurate classification of performance invalidity over and above accuracy scores remains understudied. Therefore, this study investigated whether combining VSVT accuracy and response latency scores would increase predictive utility beyond use of accuracy scores alone. Data from a mixed clinical sample of 163 patients, who were administered the VSVT as part of a larger neuropsychological battery, were analyzed. At least four independent criterion PVTs were used to establish validity groups (121 valid/42 invalid). Logistic regression models examining each difficulty level revealed that all VSVT measures were useful in classifying validity groups, both independently and when combined. Individual predictor classification accuracy ranged from 77.9 to 81.6%, indicating acceptable to excellent discriminability across the validity indices. The results of this study support the value of both accuracy and latency scores on the VSVT to identify performance invalidity, although the accuracy scores had superior classification statistics compared to response latency, and mean latency indices provided no unique benefit for classification accuracy beyond dimensional accuracy scores alone.

Acyl-CoA synthetase 1 (ACSL1) is an enzyme that converts fatty acids to acyl-CoA-derivatives for lipid catabolism and lipid synthesis in general and can provide substrates for the production of mediators of inflammation in monocytes and macrophages. Acsl1 expression is increased by hyperglycemia and inflammatory stimuli in monocytes and macrophages, and promotes the pro-atherosclerotic effects of diabetes in mice. Yet, surprisingly little is known about the mechanisms underlying Acsl1 transcriptional regulation. Here we demonstrate that the glucose-sensing transcription factor, Carbohydrate Response Element Binding Protein (CHREBP), is a regulator of the expression of Acsl1 mRNA by high glucose in mouse bone marrow-derived macrophages (BMDMs). In addition, we show that inflammatory stimulation of BMDMs with lipopolysaccharide (LPS) increases Acsl1 mRNA via the transcription factor, NF-kappa B. LPS treatment also increases ACSL1 protein abundance and localization to membranes where it can exert its activity. Using an Acsl1 reporter gene containing the promoter and an upstream regulatory region, which has multiple conserved CHREBP and NF-kappa B (p65/RELA) binding sites, we found increased Acsl1 promoter activity upon CHREBP and p65/RELA expression. We also show that CHREBP and p65/RELA occupy the Acsl1 promoter in BMDMs. In primary human monocytes cultured in high glucose versus normal glucose, ACSL1 mRNA expression was elevated by high glucose and further enhanced by LPS treatment. Our findings demonstrate that CHREBP and NF-kappa B control Acsl1 expression under hyperglycemic and inflammatory conditions.

One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue. We have previously developed novel thin-film, subdural electrode arrays with hundreds of microelectrodes over a 100-1000 mm² area to enable high-resolution mapping of neural activity. Here, we used these high-density arrays to study microscale properties of human epileptiform activity. We performed intraoperative micro-electrocorticographic recordings in nine patients with epilepsy. In addition, we recorded from four patients with movement disorders undergoing deep brain stimulator implantation as non-epileptic controls. A board-certified epileptologist identified microseizures, which resembled electrographic seizures normally observed with clinical macroelectrodes. Recordings in epileptic patients had a significantly higher microseizure rate (2.01 events/min) than recordings in non-epileptic subjects (0.01 events/min; permutation test, P = 0.0068). Using spatial averaging to simulate recordings from larger electrode contacts, we found that the number of detected microseizures decreased rapidly with increasing contact diameter and decreasing contact density. In cases in which microseizures were spatially distributed across multiple channels, the approximate onset region was identified. Our results suggest that micro-electrocorticographic electrode arrays with a high density of contacts and large coverage are essential for capturing microseizures in epilepsy patients and may be beneficial for localizing epileptogenic tissue to plan surgery or target brain stimulation.

Background: The importance of informant history in the diagnosis of mild cognitive impairment (MCI) has been emphasized. Yet, there is limited literature looking into the agreement of self- and informant- reported memory loss in MCI due to Alzheimer's disease (AD) versus cerebrovascular disease (CVD). We investigated the hypothesis that rates of concordance and discordance differ based on MCI etiology.
Method(s): Retrospective clinical data was gathered from the National Alzheimer's Coordinating Center dataset. First visits with a clinical diagnosis of MCI with a primary etiology of AD without CVD (AD MCI) or CVD without AD (CVD MCI) were included for analysis. Self- and informant-based report of memory loss were gleaned from the questions "does the subject report a decline in memory (relative to previously attained abilities?)" and "does the co-participant report a decline in subject's memory (relative to previously attained abilities?)." We excluded participants with missing self-reported or co-participant information on cognitive decline. Statistical analysis was performed using Chi-squared tests.
Result(s): A total of 1917 AD MCI and 213 CVD MCI visits from unique participants were included in the study. Compared to CVD MCI, AD MCI had a higher incidence of visits where both participant and informant noted memory loss (67.8% vs. 54.0%, p<0.0001). Compared to AD MCI, CVD MCI featured more disagreement between participant and informant, both in cases where the participant denied memory loss (17.8% vs. 12.0%, p = 0.0137) and where the informant denied memory loss (21.6% vs. 11.4%, p < 0.0001). Incidence of both participant and informant denying memory loss were similar between AD MCI and CVD MCI (8.9% vs. 6.6%, p = 0.2580).
Conclusion(s): Self- and collateral-based report of memory loss are more discordant in CVD MCI versus AD MCI. This reinforces the importance of eliciting a history from both patients and reliable informants, especially in patients with vascular risk factors and comorbidities

Background/UNASSIGNED:Although the incidence of radiographic Adjacent Segment Disease (ASD) following anterior cervical diskectomy/fusion (ACDF) or cervical disc arthroplasty (CDA) typically ranges from 2-4%/year, reportedly fewer patients are symptomatic, and even fewer require secondary surgery. Methods/UNASSIGNED:Multiple studies have documented a 2-4% incidence of radiographic ASD following either ACDF or CDA per year. However, fewer are symptomatic from ASD, and even fewer require additional surgery/reoperations. Results/UNASSIGNED:In a meta-analysis (2016) involving 83 papers, the incidence of radiographic ASD per year was 2.79%, but symptomatic disease was present in just 1.43% of patients with only 0.24% requiring secondary surgery. In another study (2019) involving 38,149 patients undergoing ACDF, 2.9% (1092 patients; 0.62% per year) had radiographic ASD within an average of 4.66 postoperative years; the younger the patient at the index surgery, the higher the reoperation rate (i.e. < 40 years of age 4.56 X reoperations vs. <70 at 2.1 X reoperations). In a meta-analysis of 32 articles focusing on ASD 12-24 months following CDA, adjacent segment degeneration (ASDeg) occurred in 5.15% of patients, but adjacent segment disease (AS Dis) was noted in just 0.2%/ year. Further, AS degeneration occurred in 7.4% of patients after 1-level vs. 15.6% following 2 level fusions, confirming that CDA's "motion-sparing" design did not produce the "anticipated" beneficial results. Conclusion/UNASSIGNED:The incidence of radiographic ASD ranges from 2-4% per year for ACDF and CDA. Additionally, both demonstrate lesser frequencies of symptomatic ASD, and the need for secondary surgery. Further, doubling the frequency of ASD following 2 vs. 1-level CDA, should prompt surgeons to limit surgery to only essential levels.

OBJECTIVE/UNASSIGNED:To explore factors associated with anticoagulation (AC) initiation after atrial fibrillation (AF) diagnosis. DESIGN/UNASSIGNED:Retrospective cohort study. SETTING/UNASSIGNED:Urban medical center. PATIENTS/UNASSIGNED:Adults with emergency department (ED) diagnosis of new onset AF from 1/1/2017-1/1/2020 discharged home. METHODS/UNASSIGNED:We compared patients initiated on AC, our primary outcome, to those not initiated on AC. Stroke, major bleeding, and AC initiation within 1 year of visit were secondary outcomes. We hypothesized that minority race and non-English language preference are associated with failure to initiate AC. RESULTS/UNASSIGNED:-VASc score (3[2-4]) vs. 2[1-4]; P=.047) were associated with AC. Of 73 patients with follow-up data at 1 year, 2 (8%) not initiated on AC had strokes, 2 (4%) initiated on AC had major bleeds, and 15 (62.5%) not initiated on AC in the ED subsequently were initiated on AC. CONCLUSION/UNASSIGNED:More than half of ED patients with new AF eligible for AC were initiated on it. Work to improve AC utilization among patients with new AF who left AMA from ED and those who prefer to communicate in a non-English language may be warranted.