Faculty Bibliography

OBJECTIVES/OBJECTIVE:The aim of this study was to determine whether MRI radiomic features of key cerebral structures differ between women and men, and whether detection of such differences depends on the image resolution. MATERIALS AND METHODS/METHODS:Ultrahigh resolution (UHR) 3D MP2RAGE (magnetization-prepared 2 rapid acquisition gradient echo) T1-weighted MR images (voxel size, 0.7 × 0.7 × 0.7 mm3) of the brain of 30 subjects (18 women and 12 men; mean age, 39.0 ± 14.8 years) without abnormal findings on MRI were retrospectively included. MRI was performed on a whole-body 7 T MR system. A convolutional neural network was used to segment the following structures: frontal cortex, frontal white matter, thalamus, putamen, globus pallidus, caudate nucleus, and corpus callosum. Eighty-seven radiomic features were extracted respectively: gray-level histogram (n = 18), co-occurrence matrix (n = 24), run-length matrix (n = 16), size-zone matrix (n = 16), and dependence matrix (n = 13). Feature extraction was performed at UHR and, additionally, also after resampling to 1.4 × 1.4 × 1.4 mm3 voxel size (standard clinical resolution). Principal components (PCs) of radiomic features were calculated, and independent samples t tests with Cohen d as effect size measure were used to assess differences in PCs between women and men for the different cerebral structures. RESULTS:At UHR, at least a single PC differed significantly between women and men in 6/7 cerebral structures: frontal cortex (d = -0.79, P = 0.042 and d = -1.01, P = 0.010), frontal white matter (d = -0.81, P = 0.039), thalamus (d = 1.43, P < 0.001), globus pallidus (d = 0.92, P = 0.020), caudate nucleus (d = -0.83, P = 0.039), and corpus callosum (d = -0.97, P = 0.039). At standard clinical resolution, only a single PC extracted from the corpus callosum differed between sexes (d = 1.05, P = 0.009). CONCLUSIONS:Nonnegligible differences in radiomic features of several key structures of the brain exist between women and men, and need to be accounted for. Very high spatial resolution may be required to uncover and further investigate the sexual dimorphism of brain structures on MRI.

IMPORTANCE/UNASSIGNED:People with disabilities experience pervasive health disparities driven by adverse social determinants of health, such as unemployment. Section 14(c) of the 1938 Fair Labor Standards Act has been a controversial policy that allows people with disabilities to be paid below the prevailing minimum wage, but its impact on employment remains unknown despite ongoing national debates about its repeal. OBJECTIVE/UNASSIGNED:To estimate whether state-level repeal of Section 14(c) was associated with employment-related outcomes for people with cognitive disability. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This quasi-experimental, synthetic difference-in-differences study used individual-level data from the 2010-2019 American Community Surveys. Outcomes before and after subminimum wage law repeal in 2 states (New Hampshire and Maryland) that repealed Section 14(c) were compared with a synthetic group of control states that did not implement repeal. Individuals aged 18 to 45 years who reported having a cognitive disability were included. Data were analyzed from May 2023 to May 2024. EXPOSURE/UNASSIGNED:Repeal of Section 14(c) in New Hampshire (2015) and Maryland (2016). MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were labor force participation and employment rates. Secondary outcomes were annual wages, annual hours worked, hourly wages, and proportion earning above state minimum wage among employed individuals. RESULTS/UNASSIGNED:The sample included 450 838 individuals. Of these, 253 157 (55.7%) were male, and the mean (SD) age was 31.3 (8.4) years. In state-specific analyses, New Hampshire's labor force participation and employment had a statistically significant increase by 5.2 percentage points (β = 0.05; 95% CI, 0-0.10; P = .04) and 7 percentage points (β = 0.07; 95% CI, 0.01-0.13; P = .03), respectively, following Section 14(c) repeal. Labor force participation and employment both increased in Maryland, although estimates were not statistically significant. Pooling both states, Section 14(c) repeal was associated with a statistically significant 4.7-percentage point (β = 0.05; 95% CI, 0.01-0.08; P = .01) increase in labor force participation and a nonsignificant 4.3-percentage point (β = 0.04; 95% CI, 0-0.09; P = .07) increase in employment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, repeal of Section 14(c), a policy allowing subminimum wages for people with disabilities, led to increases in labor force participation, though with heterogeneity at the state level. These findings suggest the importance of state-level factors in shaping program effects, especially as national-level Section 14(c) repeal is being debated.

With the growth of the older adult population, the number of older adults waitlisted for and undergoing kidney and liver transplantation has increased. Transplantation is an important and definitive treatment for this population. We present a contemporary review of the unique preoperative, intraoperative, and postoperative issues that patients older than 65 y face when they undergo kidney or liver transplantation. We focus on geriatric syndromes that are common in older patients listed for kidney or liver transplantation including frailty, sarcopenia, and cognitive dysfunction; discuss important considerations for older transplant recipients, which may impact preoperative risk stratification; and describe unique challenges in intraoperative and postoperative management for older patients. Intraoperative challenges in the older adult include using evidence-based best anesthetic practices, maintaining adequate perfusion pressure, and using minimally invasive surgical techniques. Postoperative concerns include controlling acute postoperative pain; preventing cardiovascular complications and delirium; optimizing immunosuppression; preventing perioperative kidney injury; and avoiding nephrotoxicity and rehabilitation. Future studies are needed throughout the perioperative period to identify interventions that will improve patients' preoperative physiologic status, prevent postoperative medical complications, and improve medical and patient-centered outcomes in this vulnerable patient population.

INTRODUCTION/BACKGROUND:Blood-based biomarkers offer a promising approach for the detection of neuropathologies from repetitive head impacts (RHI). We evaluated plasma biomarkers of amyloid, tau, neurodegeneration, and inflammation in former football players. METHODS:The sample included 180 former football players and 60 asymptomatic, unexposed male participants (aged 45-74). Plasma assays were conducted for beta-amyloid (Aβ) 40, Aβ42, hyper-phosphorylated tau (p-tau) 181+231, total tau (t-tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), Aβ42/p-tau181 and Aβ42/Aβ40 ratios. We evaluated their ability to differentiate the groups and associations with RHI proxies and traumatic encephalopathy syndrome (TES). RESULTS:= 0.008). DISCUSSION/CONCLUSIONS:Plasma p-tau181 and p-tau231, GFAP, and NfL may offer some usefulness for the characterization of RHI-related neuropathologies. HIGHLIGHTS/CONCLUSIONS:Former football players had higher plasma p-tau181 and p-tau231 and lower Aβ42/ptau-181 compared to asymptomatic, unexposed men. Younger age of first exposure was associated with increased plasma NfL and GFAP in older but not younger participants. Plasma GFAP was higher in participants with TES-CTE possible/probable compared to TES-CTE no/suggestive.

Background Patients with neuromyelitis optica spectrum disorder (NMOSD) are often seropositive for antibodies against aquaporin-4 (AQP4). The importance of MRI monitoring in this disease requires evaluation. Purpose To profile MRI features from a large international cohort with AQP4 immunoglobulin G (IgG)-seropositive NMOSD (from the Parallel MRI in NMOSD [PAMRINO] study) and to evaluate and confirm existing knowledge regarding the incidence, location, and longitudinal development of characteristic lesions in the central nervous system associated with AQP4-IgG-seropositive NMOSD. Materials and Methods In this retrospective study (from August 2016 to January 2019), MRI and clinical data were collected from 17 NMOSD expert sites in 11 countries across four continents. Clinical features and lesions identified at cross-sectional and longitudinal MRI were assessed. No formal statistical tests were used to compare observations; however, means, SDs, and 95% CIs are reported when evaluating lesion frequencies. Results Available T1-weighted and T2-weighted MRI scans in patients with AQP4-IgG-seropositive NMOSD (n = 525) were read. Among the 525 patients, 320 underwent cerebral MRI examinations with T2-weighted hyperintense cerebral (264 of 320; 82.5%), cerebellar (44 of 320; 13.8%), and brainstem (158 of 321 [49.2%], including one lesion observed at cervical spinal cord [SC] MRI) lesions. Lesions in the optic nerves, analyzed from 152 MRI examinations, were mainly found in the central (81 of 92; 88%) and posterior (79 of 92; 86%) sections (bilaterally in 39 of 92; 42%). Longitudinally extensive transverse myelitis was the predominant SC lesion pattern (upper compartment from 322 MRI examinations, 133 of 210 [63.3%]; and lower compartment from 301 MRI examinations, 149 of 212 [70.3%]). However, nonlongitudinal extensive transverse myelitis lesions were also observed frequently (105 of 210; 50.0%) in the cervical SC. Clinical data (n = 349; mean age, 44 years ± 14 [SD]; 202 female patients) and acute lesions at contrast-enhanced (CE) MRI (n = 58, performed within 30 days of the last attack) were evaluated. CE lesions were detected in the cerebrum (eight of 13; 62%), optic nerves (14 of 19; 74%), or chiasm (three of four; 75%) within 15 days of any relapse. In the upper SC (29 of 44; 66%), CE lesions were frequently observed up to 20 days after a clinical myelitis event. Conclusion A high incidence of abnormal brain MRI examinations and nonlongitudinal extensive SC lesions was found in patients in PAMRINO with AQP4-IgG-seropositive NMOSD. © RSNA, 2024 Supplemental material is available for this article.

INTRODUCTION/BACKGROUND:Anti-amyloid antibody therapies such as lecanemab are increasingly being used to treat Alzheimer's disease (AD). These therapies are associated with a high rate of amyloid-related imaging abnormalities (ARIA). METHODS:We review the case history of a patient who developed ARIA associated with lecanemab treatment. RESULTS:In addition to microhemorrhages and cerebral edema that are recognized features of ARIA, the patient developed several ischemic strokes. The patient also experienced frequent electrographic seizures without overt clinical seizures. The patient demonstrated clinical and radiographic improvement after steroid treatment. DISCUSSION/CONCLUSIONS:Our case suggests that ischemic strokes may be a feature of ARIA and highlights the importance of having a high clinical suspicion for seizures in ARIA. As anti-amyloid therapies are likely going to be increasingly used to treat AD, it is important to appreciate the spectrum of clinical and radiographic findings that can result as side effects from this class of therapies. HIGHLIGHTS/CONCLUSIONS:We report a patient who developed severe amyloid-related imaging abnormalities (ARIA) after treatment with lecanemab. Our report suggests that ischemic strokes may be a novel imaging feature of ARIA. Our report highlights the need for high clinical suspicion for seizures in ARIA.

The tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. The primary tauopathies meet the definition of rare diseases in the United States. There is no approved treatment for primary tauopathies. In this context, designing the most efficient development programs to translate promising targets and treatments from preclinical studies to early-phase clinical trials is vital. In September 2022, the Rainwater Charitable Foundation convened an international expert workshop focused on the translation of tauopathy therapeutics through early-phase trials. Our report on the workshop recommends a framework for principled drug development and a companion lexicon to facilitate communication focusing on reproducibility and achieving common elements. Topics include the selection of targets, drugs, biomarkers, participants, and study designs. The maturation of pharmacodynamic biomarkers to demonstrate target engagement and surrogate disease biomarkers is a crucial unmet need. HIGHLIGHTS: Experts provided a framework to translate therapeutics (discovery to clinical trials). Experts focused on the "5 Rights" (target, drug, biomarker, participants, trial). Current research on frontotemporal degeneration, progressive supranuclear palsy, and corticobasal syndrome therapeutics includes 32 trials (37% on biologics) Tau therapeutics are being tested in Alzheimer's disease; primary tauopathies have a large unmet need.

BACKGROUND:Although it is well-known that intracerebral hemorrhage (ICH) is associated with physical and psychological morbidity, there is scant data on factors influencing social engagement after ICH. Understanding the relationship between functionality, psychological outcome and social engagement post-bleed may facilitate identification of patients at high risk for social isolation after ICH. METHODS:Patients ≥18-years-old with non-traumatic ICH from January 2015-March 2023 were identified from the Neurological Emergencies Outcomes at NYU (NEON) registry. Data on discharge functionality were collected from the medical record. 3-months post-bleed, patients/their legally-authorized representatives (LARs) were contacted to complete Neuro-QoL social engagement, anxiety, depression, and sleep inventories. Patients were stratified by ability to participate in social roles and activities (good=T-score>50, poor=T-score≤50) and satisfaction with social roles and activities (high=T-score>50 and low=T-score≤50). Univariate comparisons were performed to evaluate the relationship between post-bleed social engagement and both functionality and psychological outcome using Pearson's chi-square, Fisher's Exact test, and Mann-Whitney U tests. Multivariate logistic regression was subsequently performed using variables that were significant on univariate analysis (p<0.05). RESULTS:The social engagement inventories were completed for 55 patients with ICH; 29 (53 %) by the patient alone, 14 (25 %) by a LAR alone, and 12 (22 %) by both patient and LAR. 15 patients (27 %) had good ability to participate in social roles and activities and 10 patients (18 %) had high satisfaction with social roles and activities. Social engagement was associated with both functionality and psychological outcome on univariate analysis, but on multivariate analysis, it was only related to functionality; post-bleed ability to participate in social roles and activities was associated with discharge home, discharge GCS score, discharge mRS score, and discharge NIHSS score (p<0.05) and post-bleed satisfaction with social roles and activities was related to discharge mRS score and discharge NIHSS score (p<0.05). CONCLUSION/CONCLUSIONS:In patients with nontraumatic ICH, social engagement post-bleed was related to discharge functionality, even when controlling for depression, anxiety, and sleep disturbance.