Faculty Bibliography

INTRODUCTION/BACKGROUND:This study aimed to explore the experience of living with amyotrophic lateral sclerosis (ALS) and to develop a conceptual model for this rare disease. METHODS:Concept elicitation interviews were conducted (January-September 2024) with people living with ALS (PLwALS; n = 31), caregivers (n = 20), and clinicians (n = 10). Qualitative data were analyzed separately to develop a conceptualization of the experience of living with ALS. Concept saturation was assessed every 5-6 interviews, and a conceptual model was developed. RESULTS:The mean age of PLwALS was 42.4 years (standard deviation [SD] 11.5), 81% were female, 84% were white, and 23% had SOD1-ALS. The mean time since diagnosis was 4.6 years (SD 4.2); mean normed Rasch Overall ALS Disability Scale score was 76 (SD 17.16). Signs, symptoms, and functions reported during PLwALS interviews included neuromuscular, bulbar, speech, neurocognitive (e.g., memory issues), and a range of physical functioning issues (e.g., motor coordination). PLwALS also reported impacts on a range of activities and psychosocial interactions (e.g., eating, depressed mood, and relationships), alongside management strategies they employed. Interviews with caregivers and clinicians supported findings from the PLwALS interviews. Caregivers also identified signs such as drooling/excess salivation, and impacts related to ALS management (e.g., need for writing aids). Clinicians additionally considered loss of speech and neurocognitive signs (e.g., behavior/personality change) as ALS clinical manifestations. Concept saturation was reached, and a consolidated, comprehensive conceptual model was developed. CONCLUSION/CONCLUSIONS:This research provides a holistic understanding of the experience of living with ALS and is the first conceptual model based on in-depth concept elicitation interviews. The findings highlight the range of signs, symptoms, and impacts that PLwALS experience, emphasizing its serious humanistic impact and high unmet need, and will help to guide patient-centric evaluation of clinical outcome assessments in future ALS studies.

BACKGROUND:Glioblastoma intramedullary spinal cord metastasis (GISCM) is a rare sequela of high-grade astrocytoma and glioblastoma multiforme (GBM). Discrete intramedullary spinal cord metastases are less common than spinal leptomeningeal spread and may follow a more indolent course. Once identified as GISCM, palliative maximal safe resection of the tumor may be considered to alleviate neurological symptoms. Reports describing the surgical management of these rare lesions, including the use of emerging technologies that may aid in maximal safe resection, are sparse. A further understanding is also required regarding the course of disease and factors contributing to mortality in GISCM. METHODS:We reviewed the intraoperative management and clinical course of three patients treated for GISCM at our institution between 2015 and 2024. We additionally conducted a PRISMA-guided systematic literature review of PubMed Central, MEDLINE, and Bookshelf databases through May 26th, 2025, including original patient reports of GISCM from cranial astrocytoma or GBM. The disease course, management strategies, and causes of mortality in previously reported cases were analyzed. RESULTS:Our institutional cohort had a mean time to spinal metastasis of 26.2 months from diagnosis of cranial disease (range 17.5-40.5 months), with a mean survival of 9.2 months following maximal safe resection of extramedullary components (range 7-12 months). In two cases, intraoperative Stimulated Raman Histology (SRH) was employed to facilitate the rapid identification of metastatic GBM, thereby influencing surgical strategy. In one case, 5-aminolevulinic acid (5-ALA) was used to differentiate between tumor and spinal cord parenchyma, facilitating maximal safe debulking without neurological injury. Literature review identified 38 prior reported cases of GISCM, with a median time to spinal diagnosis of 11.0 months and a median survival of 3.5 months thereafter. The cause of death in the review cohort often involved multiple factors, and when analyzed for contributing factors to death, 38.7% involved cranial progression, 38.7% involved progression of spinal disease, and 29.0% involved medical complications. Gait ataxia at presentation was associated with shorter survival in review patients, potentially reflecting advanced disease with extramedullary cord compression. CONCLUSION/CONCLUSIONS:GISCM represents an entity distinct from leptomeningeal disease and may be managed in conjunction with recurrent cranial disease. Surgical debulking is a technically feasible strategy that can be safely facilitated using tools employed in the management of intracranial GBM, facilitating maximal safe resection without compromising survival.

OBJECTIVES/UNASSIGNED:The adverse mental health effects of racism are well documented among Asian American communities, yet little is known about how internalized racism (IR) affects mental health among Asian American women, an underserved group. This study examines perceived stress and resilience as potential mechanism and moderator, respectively, in the relationship between IR and mental health outcomes (depression and anxiety). DESIGN/UNASSIGNED:Using a cross-sectional design, we included a sample of 349 Asian American adult women. Mediation analyses tested whether perceived stress mediated the association between IR and mental health. Moderated mediation analyses examined whether resilience moderated the indirect effects of IR on mental health via stress. RESULTS/UNASSIGNED:Perceived stress significantly mediated the relationship between IR and both depression and anxiety. The indirect effect was significant for depression (b = 1.25, Boot Standard Error (SE) = 0.44, 95% Confidence Interval [CI]: 0.44, 2.13) and anxiety (b = 1.15, Boot SE = 0.40, 95% CI: 0.40, 1.95), while direct effects were not significant. Resilience moderated the indirect effect of IR on depression (index = -0.30, 95% CI: -0.59, -0.09) and anxiety (index = -0.17, 95% CI: -0.33, -0.03), with weaker indirect effects observed at higher levels of resilience. CONCLUSION/UNASSIGNED:Perceived stress is a key mechanism linking IR to depression and anxiety among Asian American women. Resilience attenuates the impact of IR on both mental health outcomes. These findings highlight the importance of culturally tailored interventions that target stress reduction to reduce mental health disparities in this underserved population.

Chromosomal rearrangements on the short arm of Chromosome 8 cause 8p syndrome, a rare developmental disorder characterized by neurodevelopmental delays, epilepsy, and cardiac abnormalities. Although significant progress has been made in managing the symptoms of 8p syndrome and other conditions caused by large-scale chromosomal aneuploidies, no therapeutic approach has yet been demonstrated to target the underlying disease-causing chromosome. Here, we establish a two-step approach to eliminate the abnormal copy of Chromosome 8 and restore euploidy in cells derived from an individual with a complex rearrangement of Chromosome 8p. Transcriptomic analysis revealed 361 differentially expressed genes between the proband and the euploid revertant, highlighting genes both within and outside the 8p region that may contribute to 8p syndrome pathology. Furthermore, we demonstrate that the proband exhibits a significant defect in neural differentiation that could be partially rescued by treatment with small-molecule inhibitors of cell death. Our work demonstrates the feasibility of using chromosome engineering to correct complex aneuploidies in vitro and establishes a platform to further dissect the pathophysiology of 8p syndrome and other conditions caused by chromosomal rearrangements.

PURPOSE/OBJECTIVE:Responsive neurostimulation (RNS) is an effective therapeutic option for drug-resistant focal epilepsy, especially when the seizure onset zone lies in an eloquent cortex. However, the safety, tolerability, efficacy, as well as optimal stimulation and detection settings for RNS therapy in the primary motor cortex are poorly understood. METHODS:We performed a multi-center retrospective cohort study to assess the safety and efficacy of treatment with RNS targeting the primary motor cortex in patients with drug-resistant focal motor epilepsy. RESULTS:A total of 20 patients were included in the study. Overall, 79 % of the patients achieved ≥ 50 % seizure reduction at a mean follow-up time of 58.4 months, while 53 % of the patients achieved ≥ 90 % seizure reduction. None of the patients had any complications from the surgical implantation of the RNS device. There were no reported adverse side effects from neurostimulation therapy of the primary motor cortex. CONCLUSION/CONCLUSIONS:For individuals with drug-resistant focal motor epilepsy, treatment with RNS of the primary motor cortex is safe, effective, and well-tolerated.

CONTEXT/BACKGROUND:More health systems are establishing outpatient palliative care (PC) programs, increasing demand for ambulatory PC clinicians. However, existing outpatient training during hospice and palliative medicine (HPM) fellowship remains limited and suboptimal. Little is known about the outpatient-specific knowledge and skills PC trainees should acquire for competent outpatient practice. OBJECTIVES/OBJECTIVE:To identify and prioritize outpatient-focused educational topics for HPM fellows and clinicians new to ambulatory practice. METHODS:A cross-sectional survey of United States (U.S.) outpatient PC clinicians (physicians, advanced practice practitioners [APPs]). Using a list of 51 educational topics, respondents selected a maximum of 20 topics they would prioritize as essential to prepare learners for outpatient practice. RESULTS:Of 247 clinicians, 136 (55%) responded, including 115 physicians and 21 APPs from all U.S. regions. Seven of 51 topics were prioritized by more than two-thirds of respondents (n = 92-119, 68%-86%). Four focused on outpatient application of core PC skills (pain management [n = 113, 83%], nonpain symptom management [n = 117, 86%], depression/anxiety [n = 107, 79%], goals of care [n = 92, 68%]). The remaining three covered discrete topics related to pain and opioid management, including best practices for caring for patients with comorbid pain and substance use disorder (n = 104, 76%). CONCLUSION/CONCLUSIONS:This national survey identified foundational outpatient-focused educational topics for HPM learners and suggests that outpatient curricula prioritize deliberate education on the unique application of core PC skills in outpatient settings. This prioritized list provides education leaders a roadmap to enhance existing curricula and informs the development of outpatient educational resources that can be shared across institutions.

INTRODUCTION/BACKGROUND:Plasma phosphorylated tau 217 (p-tau217) is a leading blood-based biomarker of Alzheimer's disease. Its performance in underrepresented racial/ethnic groups remains insufficiently characterized. METHODS:We analyzed 2798 participants from the Health and Aging Brain Study-Health Disparities, including non-Hispanic White, non-Hispanic Black, and Hispanic adults. Multivariable logistic regression and receiver operating characteristic analyses assessed associations and discriminative accuracy between plasma p-tau217 and clinical cognitive impairment with racial/ethnic-specific thresholds. RESULTS:Across all groups, p-tau217 levels were higher in cognitively impaired than unimpaired participants. Elevated p-tau217 was associated with greater odds of cognitive impairment in all racial and ethnic groups. Discriminative accuracy was modest but significant (area under the curve 0.65-0.72), with highest performance in non-Hispanic Black and lowest in Hispanic participants. DISCUSSION/CONCLUSIONS:Plasma p-tau217 is robustly associated with cognitive impairment across diverse populations with varying thresholds, highlighting the need for population-specific calibration to support equitable biomarker implementation.

OBJECTIVES/OBJECTIVE:To summarize and provide clinical insights on the most impactful publications related to critical care pharmacotherapy in 2025. METHODS:A systematic search of PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE) was conducted between January 1, 2025 and October 5, 2025. Inclusion criteria consisted of randomized controlled trials with prospective study designs evaluating a critically ill adult patient population receiving pharmacotherapeutic interventions and reporting clinical endpoints. A multi-disciplinary and geographically diverse group of critical care clinicians was assembled and an a-priori defined three-round modified Delphi process was performed, with a focus on the publications determined to be the most impactful or novel. RESULTS:The systematic search yielded a total of 1609 articles for review and 1566 were excluded, leaving 43 articles to be included in the modified Delphi process. In each round, articles were scored based on their overall contribution to the literature and novelty with articles achieving a score at or above the median progressing to the next modified Delphi round. The six included articles are summarized. Article topics include alternative sedation options in mechanically ventilated patients, thrombolytic usage in acute ischemic strokes, management of coagulopathic bleeding following cardiac surgery, and use of corticosteroids in severe community-acquired pneumonia. CONCLUSIONS:This concise review identified, summarized, and offered insights on the most relevant critical care pharmacotherapy publications in the year 2025.

Imaging-based staging is a key component of renal cell carcinoma (RCC) management, yet anatomic labels alone do not fully capture tumor biology. This review highlights key aspects of RCC staging using computed tomography (CT) and magnetic resonance imaging (MRI), compares their use across major guidelines, and explores how integrating imaging-based prognostic markers can refine preoperative risk assessment. We summarize the pragmatic use of multiphase CT and MRI for T-staging, highlight pitfalls, and outline indications for chest and ancillary imaging based on American Urological Association, European Association of Urology, and National Comprehensive Cancer Network guidelines. We also discuss imaging-based prognostic biomarkers, including central non-enhancement and enhancement heterogeneity, diffusion metrics, and radiomic signatures, and we describe how they correlate with outcomes such as tumor grade, stage, molecular features, and survival. In addition, we dive into future directions, focusing on the potential integration of advanced technologies (e.g., photon counting CT, ⁸⁹Zr-Girentuximab positron emission tomography/CT), integration with liquid biopsy, and development of standardized reporting systems focusing on cancer likelihood and aggressiveness (e.g., Kidney Imaging Reporting and Data System). By bridging staging descriptors with prognostic phenotypes, we aim to standardize reports, better inform management, and improve decision-making for patients with RCC.