Faculty Bibliography

BACKGROUND/UNASSIGNED:The long-term efficacy and safety of vutrisiran in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) were assessed in the HELIOS-A randomized treatment extension (RTE). METHODS/UNASSIGNED:Patients who completed the 18-month, phase 3, open-label HELIOS-A study could enter an open-label RTE with re-randomization 1:1 to vutrisiran 25 mg every 3 months (Q3M) or 50 mg every 6 months (Q6M; transitioned to 25 mg Q3M following an amendment) for up to 42 months (RTE M18 efficacy assessment; RTE M42 safety and transthyretin (TTR) levels). RESULTS/UNASSIGNED: = 73]). Mean serum TTR reduction from study baseline at RTE M42 for the total vutrisiran group was 84.5%. Efficacy was sustained from RTE baseline through RTE M18 in modified Neuropathy Impairment Score +7, Norfolk Quality of Life-Diabetic Neuropathy score, 10-meter walk test, Rasch-built Overall Disability Scale and modified body mass index (mBMI); most patients (67.8%) had stable polyneuropathy disability scores. Most AEs were mild/moderate in severity with no new safety concerns. CONCLUSIONS/UNASSIGNED:Results from the HELIOS-A RTE demonstrate relative stability with only modest changes in disease activity, sustained serum TTR reductions, and an acceptable safety profile with long-term vutrisiran treatment in patients with ATTRv-PN. UNLABELLED:ClinicalTrials.gov: NCT03759379.

INTRODUCTION/UNASSIGNED:Since the establishment of Pain Medicine (PM) as an ACGME-recognized subspecialty in 1992, the field has undergone significant transformation. These changes brought increasing diversity in applicants` primary specialties, and the introduction of a myriad of emerging treatment paradigms. In this study, we aimed to evaluate the expectations, experiences, and perspectives of three target groups-PM trainees, program directors (PDs), and employers-to guide the evolution of PM education. METHODS/UNASSIGNED:This study employed an integrated survey approach to comprehensively evaluate PM fellowship training. Surveys were distributed through professional societies, verified forums, and direct outreach over separate 3-month periods in 2023 for PD and trainee surveys and in 2024 for the employer survey. A total of 518 respondents across PDs, employers, and trainees completed surveys; overall response rate was indeterminable due to unknown denominators, while the PD survey response rate was 69.0%. RESULTS/UNASSIGNED:The survey findings highlighted both shared and unique perspectives among the stakeholder groups. Trainees emphasized procedural volume and diversity as critical motivators for fellowship selection. Despite this focus, 70% of trainees expressed reluctance toward extending their fellowship duration, with 50% of trainees favored private practice. PDs acknowledged variability in training quality and emphasized the importance of supplemental workshops to address procedural gaps. Vast majority of PDs supported extending the fellowship duration to mitigate reliance on industry-led supplemental education. Employers underscored significant deficiencies in graduates' preparedness for independent practice, with only 7% considering fellows adequately trained under the current model. Across all groups, there was a consensus on the need for curriculum standardization and enhanced training to align with the growing complexity of PM. CONCLUSION/UNASSIGNED:This study suggests that the one-year fellowship can be re-evaluated for adequacy in preparing physicians for independent practice, particularly in advanced procedures. Alternative training pathways offer additional exposure but vary in structure and oversight.

We sought to generate recommendations for the tennis community regarding the provision of mental healthcare and the promotion of mental wellness among elite tennis athletes, including junior tennis athletes. Recommendations were generated using a multimethod approach that included an in-person summit held during the 2022 US Open Tennis Championships in New York, New York, USA, and an asynchronous Delphi consensus process. Participants (n=83) were purposively selected to ensure diverse representation from all seven governing bodies of tennis and the broader tennis ecosystem, including: current and former elite adult and junior players, coaches, sport administrators, parents, physiotherapists, athletic trainers, physicians (sports medicine, psychiatry, neurology), other licensed mental health providers, epidemiologists and other academic subject matter experts. The summit included expert presentations and cross-organisation group discussion, which were used to generate provisional consensus statements. Statements were rated anonymously and refined iteratively based on synthesis of open-ended feedback until predetermined numeric thresholds were reached. The summit also included discussion of implementation challenges and priorities. As a result of this process, 2 foundational principles and 25 actionable recommendations were adopted, covering 5 domains: (1) standards of care, (2) education, (3) media and social media, (4) safeguarding and (5) research. The foundational principles emphasised that mental health must be prioritised by tennis governing bodies and that these bodies should collaborate across the tennis ecosystem. This output is a starting point for coordinated mental health efforts in tennis. More broadly, this pragmatic process is a replicable model for cross-organisational collaboration in other high-performance sports.

PURPOSE OF REVIEW/OBJECTIVE:Balance depends on accurate perception of self-motion and verticality and on multisensory integration for stance, and gait. In Parkinson's disease, balance is commonly impaired and variably affected by treatment. Although vestibular and multisensory contributions are increasingly recognized, progress is limited by fragmented evidence, inconsistent methods, and artifact-prone measures. We provide a consensus roadmap across four domains - video-oculography/vHIT, VEMPs, posturography, and perceptual paradigms - to improve clinical translation of balance research in Parkinson's disease. RECENT FINDINGS/RESULTS:An interdisciplinary taskforce conducted a comprehensive literature review and a modified Delphi process (≥80% agreement), using virtual meetings, surveys, and an in-person consensus session. Oculography/vHIT shows largely preserved aVOR in Parkinson's disease but is vulnerable to Parkinson's disease specific artifacts, requiring standardization. VEMPs relate to brainstem and non-motor features but are limited by EMG-dependent confounds. Posturography reveals impaired multisensory integration with visual dependence and cholinergic contributions; reactive-capacity measures outperform sway alone. Perceptual paradigms show task-specific distortions and increased variability linked to axial/postural syndromes. SUMMARY/CONCLUSIONS:This consensus offers a practical roadmap, de-emphasize aVOR/vHIT as primary unsteadiness outcomes; use VEMPs as ancillary measures; prioritize posturography probing adaptability and reactive stepping; integrate wearables and neurochemical imaging; and adopt consortium-level minimum datasets to enable reproducible, phenotype-aware advances in Parkinson's disease balance research.

Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45-74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45-74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen's d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen's d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

Human microbiome research has become pivotal in advancing our understanding of complex diseases such as diabetes, inflammatory bowel disease, and cancer. Much of this work relies on comparing microbial communities across health and disease states, or case-control cohorts, using high-throughput metagenomic sequencing. Yet the very nature of sequencing-derived microbiome data makes robust cohort design and power-based sample-size estimation unusually difficult. Unlike other omics, microbiome profiles are compositional, sparse, and often zero inflated, properties that complicate statistical modeling and inflate sample-size requirements. These challenges are further compounded by the diversity of analytical frameworks-ranging from diversity indices to causal inference-each built on different statistical assumptions and optimized for a distinct research hypothesis. This review synthesizes current approaches around the study design and sample-size estimation in microbiome research, aiming to provide clinicians and researchers with practical guidance for navigating the statistical complexities unique to this field.

A 43-year-old woman was found to have prominent cerebellar and basal ganglia calcifications. History and examination were notable for numerous self-reported neuropsychiatric symptoms and slight abnormalities in cognitive and motor testing. Genetic testing revealed a novel likely pathogenic variant in the XPR1 gene, that represents the first heterozygous in-frame deletion likely associated with primary brain calcifications. The first objective of this report is to describe this novel variant and its associated phenotype. The second objective is to interpret the patient's symptoms and imaging abnormalities in relation to current knowledge in systems neuroscience and theoretical neurology of the basal ganglia and cerebellum.