Faculty Bibliography

[This corrects the article DOI: 10.3389/fnut.2021.748847.].

BACKGROUND:In vivo biomarkers that can detect long-term neuropathologies from repetitive head impact (RHI) exposure are needed, especially for the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). Here, we evaluated plasma p-tau217 as a potential biomarker for CTE p-tau pathology, and examined the concordance between plasma p-tau217 and Aβ pathology in an at-risk for CTE sample. METHOD/METHODS:The sample included 180 male former football players (120 professional, 60 college), and 56 asymptomatic men without RHI (i.e., controls). Participants completed blood draws, 18F-florbetapir (Aβ+=SUVR≥1.10), and 18F-flortaucipir PET. Traumatic encephalopathy syndrome (TES) diagnoses were made. Single molecule array for plasma p-tau217 (ALZpath) was performed (≥0.6 cutoff used to maximize sensitivity). Nine participants had post-mortem tissue. ANCOVA examined group differences in p-tau217 (football vs controls; TES-CTE no, TES-CTE suggestive, TES-CTE possible/probable). Multivariable regression models tested associations between p-tau217 and florbetapir/flortaucipir PET. Covariates included age, race and APOE e4. RESULT/RESULTS:Sample characteristics are in Table 1. p-tau217 concentrations were higher in former football players compared to controls (est. marginal mean difference=-0.217, p = 0.005). There were no group differences in Aβ-PET SUVR. No differences were found across TES-CTE certainty levels. In football players, higher p-tau217 was associated with higher Aβ-PET SUVR (B=1.380, 95%CI[0.597-2.155], p = 0.001) but not when Aβ+ (n = 17) participants and those with kidney/liver disease (n = 5) were excluded. Aβ+ participants had the highest p-tau217 (Figure 1). When compared against Aβ-PET, several false Aβ-positives (high p-tau217, Aβ-) were identified, including one extreme outlier (assay related) and a cluster of Aβ- participants with p-tau217 between 0.60-1.0. There were no associations with flortaucipir SUVR (frontal, mesial temporal, left parietal). Two extreme p-tau217 outliers had autopsy-confirmed CTE stage III (AD-, Table 2). Of the remaining donors, all were AD- and four had CTE (stages II-IV) with ptau217 between 0.125-0.449. CONCLUSION/CONCLUSIONS:Plasma p-tau217 has usefulness in quantifying Aβ pathology but restricted utility for detection of CTE. In this at-risk for CTE sample, p-tau217 and Aβ-PET were associated at the group level. At the individual level, false Aβ-positives (and negatives) existed, including Aβ- participants with high p-tau217. We will explore whether this discrepancy is due to disease or peripheral interference with the N-terminal binding in p-tau assays.

BACKGROUND AND PURPOSE/OBJECTIVE:Patients with intracranial stenosis-related large-vessel occlusion (ICAS-LVO) may experience better outcomes with stent placement compared with stand-alone mechanical thrombectomy (MT). This study evaluates the safety and clinical outcomes of self-expanding stents (SES) versus balloon-mounted stents (BMS) in patients with ICAS-LVO treated with MT and stent placement. MATERIALS AND METHODS/METHODS:This secondary analysis of the Registry of Emergent Large-Vessel Occlusion Due to Intracranial Stenosis, a multicenter observational study, included patients with ICAS-LVO from 25 stroke centers who underwent stent placement. Patients were stratified by stent type (SES or BMS). The primary end point was 90-day mRS = 0-2. Secondary outcomes included successful reperfusion, recurrent stroke, and infarct volume. Symptomatic intracranial hemorrhage was the primary safety outcome. Inverse probability-weighting was adjusted for confounders. RESULTS:= .001), particularly in patients without prestenting angioplasty (14% versus 1%). CONCLUSIONS:SES and BMS demonstrated comparable safety and clinical outcomes in patients with ICAS-LVO. However, SES were linked to higher rates of restenosis and recurrent strokes, potentially influenced by the absence of prestenting angioplasty. Further research is needed to refine stent-placement strategies in this population.

INTRODUCTION/BACKGROUND:The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS:We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS:Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION/CONCLUSIONS:We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS/CONCLUSIONS:The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

While the physical manifestations of NF2-related schwannomatosis (NF2-SWN) have been well documented, there are a limited number of qualitative studies on health-related quality of life in NF2-SWN. The present study sought to explore the cumulative impact of symptoms, treatments, and healthcare on the quality of life of individuals with NF2-SWN. We interviewed 16 adolescent and adult patients with NF2-SWN enrolled in the INTUITT-NF2 clinical trial and 10 clinicians with NF2-SWN expertise from the United States, United Kingdom, and Australia. Analysis of patient and clinician interviews yielded five overall themes: (1) impacts on daily living, (2) impacts on life roles, (3) impacts on relationships and social integration, (4) impacts on psychological and emotional wellbeing, and (5) burden of treatment and healthcare. Multiple symptom areas contributed to impairments in quality of life across each theme. These findings reveal that quality of life in NF2-SWN is shaped not only by individual symptoms, but by their complex, cumulative impact-highlighting the urgent need for disease-specific tools and holistic care approaches that reflect the lived realities of patients across the lifespan.

BACKGROUND:Despite fall-related injuries accounting for over two-thirds of older adult trauma injuries, fall-related injuries are more likely to be under-triaged. The Score for Trauma Triage in the Geriatric and Middle-Aged (STTGMA) is an injury risk-triage tool. This study aims to validate STTGMA's accuracy in predicting fall-related mortality among older adult trauma patients and compare its predictive accuracy with the Geriatric Trauma Outcome Score (GTOS) and the Revised Trauma Score (RTS). METHODS:Using a retrospective cohort design, we selected 6,458 older adult trauma patients (aged 65 years and older) from a single institutional trauma database (2017-2023). The primary outcome variable was in-hospital death, measured as a binary variable. The primary predictor variable was the STTGMA score, measured as a continuous variable and a four-level categorical variable. The secondary predictor variables were the GTOS and the RTS. We compared the predictive accuracy (95% confidence interval (CI)) of the STTGMA, GTOS, and RTS. We further assessed the relationships between the STTGMA risk categories and time-to-death and hospital length of stay using multivariable time-varying Cox proportional hazard analysis and multivariable quantile regression analysis, respectively. RESULTS:A total of 130 patients (2.0%) died during admission, and the median hospital length of stay was 2 days. STTGMA exhibited 84% (95% CI: 77.3-89.8) accuracy in predicting in-hospital fall-related mortality, while the GTOS and RTS both exhibited 71% diagnostic accuracies. Compared to the minimal risk category, older adult trauma patients classified as low, moderate, and high risks each had significantly longer hospital stays and adjusted mortality risks, in a dose-response pattern. CONCLUSION/CONCLUSIONS:STTGMA can accurately predict in-hospital mortality and risk-stratify the length of stay and the time to death among older adult trauma patients with fall-related injuries.

OBJECTIVE:Distinctive differences in multiple sclerosis (MS) disease severity, progression, and mortality have been observed among different races. Social determinants of health (SDH) can contribute to such racial disparities. This study aims to: 1) compare Non-Hispanic White (NHW) and Black (Bl) persons with MS in terms of MS and SDH; 2) explore the impact of SDH-adjustment in the association between race and Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25-FW), 9-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT). METHODS:120 patients, self-identified as Bl (n = 60) or NHW (n = 60) persons, were included in this cross-sectional analysis from a prospectively enrolled cohort. We used parametric and non-parametric tests; logistic models were performed to select the most relevant SDH. Univariable linear regression models were used to explore differences in EDSS, T25-FW, 9-HPT, SDMT and models were adjusted for relevant SDH using propensity scores (PS). RESULTS:Significant racial disparities in adverse SDH were identified in Black persons with MS (BpwMS). BpwMS patients had a higher EDSS (β=0.66, p = 0.022), log-transformed T25-FW (β=0.16, p = 0.001), 9-HPT (β=2.89, p = 0.001) and lower SDMT (β=-5.97, p = 0.003); after PS-adjustment, associations were no longer significant except for T25-FW (β=0.13, p = 0.030) and the magnitude of all coefficients was reduced (EDSS: -27 %, T25-FW: -19 %, 9-HPT: -36 %, SDMT: -45 %). INTERPRETATION/CONCLUSIONS:More efforts are necessary to adequately address the SDH that distinguish Bl from NHW persons with MS; additional unknown or unmeasured variables, including biologic differences as well as other SDH, should be explored to elucidate the mechanisms behind worse MS outcomes in BpwMS.

Language comprehension involves the prediction of upcoming linguistic units across multiple timescales. However, how this prediction process is hierarchically implemented in the human brain remains unclear. Combining natural language processing (NLP) and functional magnetic resonance imaging (fMRI) in a narrative comprehension task, we first applied the group-based general linear model (gGLM) to identify the neural underpinnings associated with anticipating upcoming words and sentences. Our results revealed a cortical hierarchy supporting linguistic prediction, extending from the superior temporal cortices to the default mode network (DMN). Next, we investigated how the word and sentence levels interact by testing two rival hypotheses: the continuous updating hypothesis posits that higher-level regions are updated continuously as inputs unfold over time, while the sparse updating hypothesis states that higher-level regions are updated only at the boundaries of their preferred timescales. Using computational modeling and autocorrelation analysis, we found that the sparse model outperformed the continuous model, with updating occurred at the sentence boundaries. Together, our results extend evidence for linguistic prediction to longer timescales and elucidate the neurocomputational mechanisms of hierarchical information updating in the human brain.

Aim To compare the clinical outcome and in-hospital complication risk with chemotherapy and without chemotherapy in patients with inflammatory and immune myopathies (IIM). Methods We obtained data for IIM patients admitted to hospitals in the United States from 2017 to 2018 with a primary diagnosis of IIM using a large national database. We determined the rate and pattern of utilization of associated in-hospital outcomes of chemotherapy in this patient population. Results A total of 5,360 patients had IIM, of which 315 (5.8%) received chemotherapy for the underlying malignancies and 5,045 (94.2%) did not. No significant racial or gender discrepancies were observed between the two groups. Patients who received chemotherapy had more in-hospital complications, including sepsis [79 (25.1%) vs. 585 (11.6%), p<0.01] and acute kidney injury [75 (23.8%) vs. 665 (13.2%), p<0.01]. The number of deaths was higher in the chemotherapy group [125 (39.7%) vs. 190 (3.8%)]. Further analysis of patients who died in the chemotherapy group showed that myocardial infarction [20 (6.3%)] and pneumonia [45 (14.3%)] were the leading causes of death. Conclusion In hospitalization complications such as sepsis and acute kidney injury were higher in patients who received chemotherapy in IIM patients; however, patients who died had a higher risk of myocardial infarction and pneumonia, so routine cardiac and pulmonary evaluation should be done during hospitalization of this patient population.