Faculty Bibliography

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.

High intensity (HI) binge drinking has emerged as a high-risk drinking phenotype in young adult drinkers, yet few studies have evaluated clinically meaningful correlates of HI binge drinking among young adults at risk for co-occurring psychopathologies, such as interpersonal trauma-exposed drinkers. The present study compared three groups (i.e., HI binge, standard binge, non-binge drinkers) of interpersonal trauma-exposed college student drinkers (N = 221) on alcohol and interpersonal trauma characteristics. Results of one-way ANOVAs indicated that the HI binge group endorsed significantly greater negative alcohol-related consequences relative to the other two groups. The HI binge group endorsed significantly greater enhancement motives compared to the non-binge group, and no group differences were detected for PTSD and interpersonal trauma characteristics. Individuals who engage in HI binge drinking may experience greater alcohol problems due to their use of alcohol to enhance positive mood. HI binge drinking does not differentiate individuals on the basis of interpersonal trauma experiences or related psychopathology.

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.

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.

Extracorporeal membrane oxygenation is increasingly being used to support patients with hypoxemic respiratory failure and cardiogenic shock. During the COVID-19 pandemic, consensus guidance recommended extracorporeal life support for patients with COVID-19-related cardiopulmonary disease refractory to optimal conventional therapy, prompting a substantial expansion in the use of this support modality. Extracorporeal membrane oxygenation was particularly integral to the bridging of COVID-19 patients to heart or lung transplantation. Limited human and physical resources precluded widespread utilization of mechanical support during the COVID-19 pandemic, necessitating careful patient selection and optimal management by expert healthcare teams for judicious extracorporeal membrane oxygenation use. This review outlines the evidence supporting the use of extracorporeal life support in COVID-19, describes the practice and outcomes of extracorporeal membrane oxygenation for COVID-19-related respiratory failure and cardiogenic shock, and proposes lessons learned for the implementation of extracorporeal membrane oxygenation as a bridge to transplantation in future public health emergencies.

Over the last decade there has been tremendous growth in the development of accelerated MD pathways that allow medical students to graduate in three years. Developing an accelerated pathway program requires commitment from students and faculty with intensive re-thinking and altering of the curriculum to ensure adequate content to achieve competency in an accelerated timeline. A re-visioning of assessment and advising must follow and the application of AI and new technologies can be added to support teaching and learning. We describe the curricular revision to an accelerated pathway at NYU Grossman School of Medicine highlighting our thought process, conceptual framework, assessment methods and outcomes over the last ten years.

BACKGROUND:Aspiration thrombectomy is one of the mainstays for stroke interventions. The Zoom 71 (Z71) aspiration catheter is unique with its angled tip. This study describes the orientation of the angled tip as it is navigated around the carotid siphon in relation to trackability. METHOD/METHODS:Prospectively collected cases involving large vessel occlusions of the anterior circulation intervened upon using the Z71 were retrospectively analyzed. 71 passes in 50 patients were analyzed with respect to Z71 tip orientation. 3 anatomical "turns" were defined as follows: "1": proximal cavernous, "2"- ophthalmic turn, and "3"-ICA terminus to M1. The tip was described as "Toward" Vs "Away" with respect to the inner curve of each turn. The tip getting "caught" was also analyzed. RESULTS:There was no preferential angled tip orientation of the Z71 as it was navigated around "Turn 1", 51 % "Away" vs 44 % "Toward", p= 0.54; "2", 46.5 % "Away" vs 53.5 % "Toward", p= 0.55; and "3", 43.7 % "Away" vs 46.5 % "Toward", p=0.63. The tip was not caught in Turn 1. It was caught up in "2" in 15.5 % of passes. "Away" at "2" got caught up in 21 % of passes vs 10.5 % for "Toward", p= 0.22. Z71 got caught up in "3" in 4.7 % of passes. "Away" was associated with getting caught in 6.5 % of passes vs 3 % for "Toward", p=0.52. Zoom 88 (Z88) usage as guide catheter may be associated with Z71 getting caught less in "2" compared to "Others", 9.3 % for Z88 vs 25 %, p= 0.07. This also applied to Turn 3, 0 % for Z88 vs 11.1 %, p=0.038. CONCLUSION/CONCLUSIONS:There is no preferential angled tip orientation of the Z71 as it navigates around the carotid siphon. The tip orientation does not appear to significantly affect navigation. Usage of Z88 as guide catheter helps with Z71 trackability around the siphon.

Compartment-specific cellular membrane protein turnover is not well understood. We show that FBXO10, the interchangeable component of the cullin-RING-ligase 1 complex, undergoes lipid modification with geranylgeranyl isoprenoid at cysteine953, facilitating its dynamic trafficking to the outer mitochondrial membrane (OMM). FBXO10 polypeptide lacks a canonical mitochondrial targeting sequence (MTS); instead, its geranylgeranylation at C953 and interaction with two cytosolic factors, cytosolic factor-like δ subunit of type 6 phosphodiesterase (PDE6δ; a prenyl-group-binding protein) and heat shock protein 90 (HSP90; a chaperone), orchestrate specific OMM targeting of prenyl-FBXO10. The FBXO10(C953S) mutant redistributes away from the OMM, impairs mitochondrial ATP production and membrane potential, and increases fragmentation. Phosphoglycerate mutase-5 (PGAM5) was identified as a potential substrate of FBXO10 at the OMM using comparative quantitative proteomics of enriched mitochondria. FBXO10 loss or expression of prenylation-deficient FBXO10(C953S) inhibited PGAM5 degradation, disrupted mitochondrial homeostasis, and impaired myogenic differentiation of human induced pluripotent stem cells (iPSCs) and murine myoblasts. Our studies identify a mechanism for FBXO10-mediated regulation of selective mitochondrial proteostasis potentially amenable to therapeutic intervention.

Severe brain injury can result in disorders of consciousness (DoC), including coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. Improved emergency and trauma medicine response, in addition to expanding efforts to prevent premature withdrawal of life-sustaining treatment, has led to an increased number of patients with prolonged DoC. High-quality bedside care of patients with DoC is key to improving long-term functional outcomes. However, there is a paucity of DoC-specific evidence guiding clinicians on efficacious bedside care that can promote medical stability and recovery of consciousness. This Viewpoint describes the state of current DoC bedside care and identifies knowledge and practice gaps related to patient care with DoC collated by the Care of the Patient in Coma scientific workgroup as part of the Neurocritical Care Society's Curing Coma Campaign. The gap analysis identified and organized domains of bedside care that could affect patient outcomes: clinical expertise, assessment and monitoring, timing of intervention, technology, family engagement, cultural considerations, systems of care, and transition to the post-acute continuum. Finally, this Viewpoint recommends future research and education initiatives to address and improve the care of patients with DoC.