Faculty Bibliography

INTRODUCTION/BACKGROUND:Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. METHODS AND ANALYSIS/METHODS:Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. ETHICS AND DISSEMINATION/BACKGROUND:This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration.

BACKGROUND:This study aimed to describe state- and urbanicity-stratified differences in three opioid use disorder (OUD) treatment metrics among Medicaid beneficiaries in 25 states that implemented Medicaid expansion under the Affordable Care Act by the end of 2014. METHODS:Using data from 2019, we identified Medicaid beneficiaries with OUD based on ICD-10 diagnosis codes. We then calculated the percentage of beneficiaries who met criteria for three metrics measuring OUD treatment quality, both overall and stratified by state and urbanicity type. The OUD treatment quality metrics considered were: (1) initiation of medication for opioid use disorder (MOUD) treatment, (2) engagement with OUD services, and (3) retention on MOUD treatment. RESULTS:Across states, we found that a median of 26.2% of beneficiaries initiated MOUD within 14 days of their OUD diagnosis date in the claims data. A median of 15.8% of beneficiaries engaged with OUD treatment services by initiating MOUD treatment within 14 days of their OUD diagnosis and receiving at least 2 distinct OUD-related services within 30 days of their MOUD initiation date. Among initiators, a median of 30.8% were retained on MOUD treatment for a minimum of 180 days. However, there was considerable heterogeneity in these three metrics across states; New Hampshire and West Virginia were found to have the highest overall performance out of the states considered. With respect to urbanicity, we found that rural and suburban areas had higher percentages of beneficiaries who met our three treatment quality metrics compared to urban areas. CONCLUSIONS:We found notable geographic differences in opioid use disorder treatment quality in the U.S. Medicaid population.

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.

BACKGROUND/UNASSIGNED:Pituitary hyperemia and gland enlargement can be cardinal features of intracranial hypotension secondary to cavernous sinus and epidural venous plexus distention. This phenomenon can therefore complicate radiographic interpretation of sellar lesions when both diagnoses co-exist. We report a unique case of a rapidly enlarging pituitary macroadenoma in the setting of a thoracic cerebrospinal fluid (CSF)-venous fistula causing symptomatic intracranial hypotension. CASE DESCRIPTION/UNASSIGNED:A 53-year-old female with no prior neurosurgical history presented with recurrent orthostatic headache. Magnetic resolution imaging revealed a pituitary lesion along with pathopneumonic signs of intracranial hypotension. The tumor grew rapidly on surveillance imaging, prompting consideration of surgery. Further work-up, however, revealed a thoracic CSF-venous fistula. Endovascular embolization of the fistula led to near-complete resolution of her symptoms and durable radiographic tumor regression. CONCLUSION/UNASSIGNED:Pituitary macroadenomas are susceptible to local hemodynamic changes occurring as a sequelae of occult CSF leak. Identification and treatment of the underlying etiology were sufficient to induce tumor regression.

Improving long-term protective immunity elicited by prime-boost vaccinations requires a deeper understanding of the immunologic outcomes of different vaccine platforms. Given the variety of platforms used to develop vaccines against SARS-CoV-2, we reasoned that SARS-CoV-2 offered an opportunity to compare vaccine platforms in humans. We used flow cytometry and single-cell transcriptomics to explore the B cell response to different homologous and heterologous vaccine regimens. We found that an adenovirus vector prime followed by a messenger RNA (mRNA) vaccine boost showed the greatest short-term B cell expansion and preferentially elicited an activated atypical B cell subset that was associated with antibody binding titers against spike protein. In contrast, an mRNA primary series followed by homologous boost induced a different activated B cell subset with more proliferative potential and high frequencies of a long-lived resting memory subset. Moreover, immunoglobulin A (IgA)-expressing memory B cells had more somatic hypermutations than the predominant IgG-expressing B cell population. This heterogeneity in vaccine-elicited B cell responses underscores the potential of tailoring vaccine regimens that combine different platforms to achieve potent and durable protection against infectious diseases.

PURPOSE OF REVIEW/OBJECTIVE:This review discusses the current state of the evidence related to the relationship between the cerebellum and epilepsy, highlighting evidence on neurostimulation of the cerebellum for treatment of epilepsy, and placing current knowledge into historical context. RECENT FINDINGS/RESULTS:The cerebellum plays an important role in certain epilepsy types, both as a key part of epileptic networks and an area that can give rise to seizures. Cerebellar stimulation as a potential treatment for drug-resistant epilepsy is a recurring, albeit niche, topic of interest. Over decades of intermittent, often highly limited investigations into this area of research, there are still more questions than answers. However, more recent preclinical insights point the way towards leveraging modern surgical techniques and technology in investigating cerebellar stimulation as a potential viable treatment approach to select types of epilepsy. SUMMARY/CONCLUSIONS:Cerebellar stimulation holds promise for improving seizure control in people with specific types of drug-resistant epilepsy. Future studies should leverage new preclinical data, along with modern technology, neurosurgical techniques, and clinical trial design, to help determine the optimal stimulation parameters, optimal stimulation targets, and optimal patient-selection for this promising area of investigation.

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.

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.