Citations

Objective To evaluate the feasibility and potential efficacy of percutaneous spinal stimulation (epidural stimulation, ES) combined with task-specific training to reduce spasticity and improve gait and balance in individuals with progressive multiple sclerosis (MS). Methods Two men with progressive MS (EDSS 6.5) underwent ES lead implantation targeting the lower spinal cord, followed by one month of rehabilitation involving 12 ES-assisted training sessions. Assessments included instrumented gait analysis, Modified Ashworth Scale (MAS), pendulum test, and static balance testing performed at baseline, and at end of the study with ES-Off and ES-On conditions. Results Participant 1, with spastic hemiparetic gait, demonstrated improved lower extremity joint kinematics and muscle activation during gait, reduced knee extensor spasticity, and enhanced functional movement patterns with ES-On. Participant 2, with significant paraparesis and minimal spasticity, showed limited gait changes but experienced marked improvements in static balance, particularly under eyes-closed conditions. No adverse events were reported. Conclusion This pilot study demonstrates the feasibility and tolerability of ES paired with task-specific training in progressive MS. Participant-specific responses were observed, including improvements in gait kinematics, neuromuscular activation, spasticity, or balance; however, spatiotemporal gait parameters did not improve. These preliminary findings highlight response heterogeneity and the need for individualized ES parameter tuning. Trial registry name and URL: https://clinicaltrials.gov/study/NCT06019611

ABSTRACT Objective Identifying and addressing pediatric hearing loss is critical to supporting a child's development. School‐based hearing screening is a mainstay of timely identification of hearing loss. The objectives of this study were to characterize the current hearing screening practices in public, charter, and private elementary schools in Minnesota. Methods This was a cross‐sectional survey with data collected between March and June 2023. Surveys assessed the presence of standardized hearing screening processes and compliance with American Academy of Audiology (AAA) or Minnesota Department of Health (MDH) guidelines. Results About 146 public schools, 43 charter schools, and 60 private schools met inclusion criteria and responded to the survey. There was a statistically significant difference in the rate of standardized screening between school types ( χ 2 = 18.06; p < 0.001). Only 10.44% ( n = 26) of schools completed hearing screenings per AAA guidelines, and even fewer, 4.82% ( n = 12), completed hearing screenings according to MDH guidelines. The odds of screening per AAA or MDH guidelines were 3.50 times higher in charter schools compared to public schools (95% CI: 1.14, 10.73) and 4.61 times higher in private schools compared to public schools (95% CI: 1.73, 12.26). Conclusion There is a lack of standardization in hearing screening processes in Minnesota elementary schools. Adherence to screening per AAA or MDH recommendations is low in all types of elementary schools. Charter and private schools were more likely than public schools to screen per AAA or MDH guidelines. Overall, our data demonstrate an opportunity for improvement in school‐based hearing screening. Level of Evidence N/A.

Abstract Importance Decline in olfactory function may be used as a predictor of cognitive decline, to enhance early detection models, improve risk stratification, and enable early intervention. Objective To assess the longitudinal association between olfactory decline, cognitive decline, and postmortem neuropathology. Design, setting and participants Retrospective longitudinal analysis with clinicopathological correlations of a prospective population-based cohort study using data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and its Brain and Body Donation Program. Participants included cognitively unimpaired individuals without parkinsonism that converted to mild cognitive impairment (MCI) and/or dementia or remained cognitively stable. Main Outcomes and Measures longitudinal change in olfaction, neuropsychiatric symptoms, motor function and memory, conversion to MCI/dementia, postmortem neuropathology Results Over a mean follow-up period of 7.7 ± 5.4 years, out of 922 participants who were cognitively unimpaired at the first cognitive conference, 643 remained cognitively unimpaired, 279 converted to MCI, and 82 developed dementia. Of these, 633 individuals had at least 2 olfactory tests. Converters showed reduced olfactory function (t=-12.6, p <0.0001), faster progression in neuropsychiatric symptom burden (t=3.42, p < 0.001), and faster decline in memory (t= -7.33, p <0.0001) prior to conversion while no significant differences were observed in motor scores between converters and non-converters. Using ROC analysis, olfactory decline, increased neuropsychiatric symptom burden, as well as motor and memory decline predicted conversion to MCI with a consistent accuracy of ∼ 70% up to 5 years before conversion, while UPSIT alone had an accuracy of ∼ 60%. Longitudinal decline in olfaction was associated with a higher burden of a-synuclein (t= -8.21, p <0.0005), tau tangle (t= -2.66, p < 0.01) and amyloid plaque burden (t= -2.85, p < 0.005) and a faster decline over time was associated with a higher burden of tau (t=5.66, p<0.0001). Conclusions and Relevance A reduction in olfactory identification ability is observed up to a decade prior to conversion to MCI and is associated with underlying burden of neuropathology markers, underscoring the value of incorporating olfactory testing in cognitively unimpaired individuals to identify those at-risk of future cognitive decline.

Abstract Pain treatments have modest effects. Health outcomes might be improved if treatments are matched to mechanisms underlying the persistence and biopsychosocial impact of an individual's pain. The International Association for the Study of Pain (IASP) defines 3 mechanistic pain descriptors presumed to involve different mechanisms—nociceptive, neuropathic, and nociplastic. Although treatments to address each descriptor have been proposed, there is no consensus on how to assign descriptors to clinical presentations. A recent consensus identified candidate clinical features to discriminate between descriptors in clinical practice and research. These need refinement to progress towards a tool. This study aimed to determine the rank and relative weight of identified clinical features to aid discrimination between mechanistic pain descriptors. Candidate clinical features (n = 196) were refined by the IASP Terminology Task Force to converge similar and remove redundant features. The Task Force (n = 24) and an expert panel (n = 39) ranked features using 1000minds conjoint analysis software and assigned weights based on discrete pairwise choices. Participants nominated from pairs of scenarios, which most likely indicated that pain aligned predominantly to a descriptor. Highest ranked features for neuropathic and nociplastic pain were aligned with IASP Clinical Criteria. Criteria for nociceptive pain have not been established. A ranked list of features shared by 2 mechanisms (indicating mixed mechanisms) was also identified. This study identified expert consensus on the highest ranked clinical features with potential to discriminate between pain descriptors, reflective of different underlying mechanisms. This study extends current frameworks by identifying and refining key discriminators for future operationalisation and validation.

Abstract Aims Heart failure is prevalent; however, there is no cost-effective screening option. Against formal echocardiography, we assessed the diagnostic performance of focused cardiac ultrasound (FoCUS), performed by novice users guided and interpreted by artificial intelligence (AI) for the assessment of left ventricular ejection fraction (LVEF). Methods and results We prospectively enrolled 496 adults referred for diagnostic echocardiography. Novice operators (without clinical or imaging experience) underwent a 4-h imaging workshop, then performed FoCUS using a point-of-care device (Philips Lumify) utilizing real-time AI-image guidance (UltraSight). Images were assessed by AI-image interpretation software (Mayo Clinic), and two expert blinded echocardiologists. Median age was 67, 39% female, and body mass index range 17–56 kg/m2. Forty-one subjects (8.3%) exhibited moderate or greater LV dilatation and 28 (5.6%) had LVEF &lt;40%. The median scan time was 4 min (IQR 3–5). Adequate views were achieved in 95.0% and 97.4% of subjects for AI interpretation and expert analysis, respectively. A two-step diagnostic screening process for low EF in which only abnormal AI reads or uninterpretable scans were reviewed by experts (15.1%) had a sensitivity 96.2%, specificity 95.4%, PPV 54.3%, and NPV 99.8%. A subsequent prospective validation study of 344 subjects demonstrated similar results (sensitivity 100%, specificity 99.4%). Conclusion In this early feasibility investigation, AI-guidance technology embedded on a handheld device, enabled novice users without clinical or imaging experience to acquire sufficient quality images to accurately assess LVEF with minimal training. The technology evaluated in this study may hold promise for AI-guidance and interpretation to facilitate low-cost screening for cardiac dysfunction.

PURPOSE 177Lu-PSMA-617 (LuPSMA) is an approved prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical therapy for men with metastatic castration-resistant prostate cancer (mCRPC). Older patients, particularly octogenarians, represent a substantial proportion of men with mCRPC but have been traditionally underrepresented in key registrational trials of LuPSMA. METHODS This retrospective multi-institutional study evaluated patients age 80 years and older with mCRPC after chemotherapy treated with ≥1 cycle of LuPSMA from August 2022 to December 2024. Clinical and demographic data were abstracted from electronic medical records. Outcomes included prostate specific antigen (PSA) response (PSA50 and PSA90), progression-free survival (PFS), overall survival (OS), and toxicities. Kaplan-Meier methods estimated PFS/OS; descriptive statistics summarized baseline and safety data. RESULTS Ninety-five patients (median age, 83 years) were included, of whom 36 (38%) and 21 (22%) had a history of cardiac disease or chronic kidney disease, respectively. Median follow-up was 24.1 months (IQR, 6.7-28.1). Patients received a median of five cycles of LuPSMA. Fifty-two (57%) and 21 (23%) patients achieved a PSA50 and PSA90, respectively. Median PFS and OS were 7.3 months (95% CI, 6.4 to 8.7) and 13.5 months (95% CI, 9.7 to 18.8), respectively. Grade ≥3 hematologic toxicities included anemia (n = 19; 20%) and thrombocytopenia (n = 4, 4%); grade ≥3 acute kidney injury occurred in one patient. Fourteen (15%) patients had dose delays, seven (7%) required reductions, and 10 (11%) discontinued therapy due to toxicity. Thirty-seven patients (39%) were hospitalized during therapy, with intensive care unit-level care required in two patients (2%), and there was one treatment-related death. CONCLUSION LuPSMA had comparable outcomes in octogenarians with mCRPC to patients on registrational trials, although 2/5 of patients required hospitalization during therapy. These findings support the feasibility and efficacy of LuPSMA in well-selected older men with mCRPC and suggest a role for closer monitoring of older patients.

Abstract Objective To evaluate the short- and long-term clinical outcomes of transcatheter aortic valve replacement (TAVR) among participants with RA and aortic stenosis compared with those without RA, using real-world data from a large multicentre registry. Methods Using the TriNetX Research Network, participants with aortic stenosis undergoing TAVR with (RA+) vs without (RA−) RA were identified. Odds ratios (ORs) with 95% CIs estimated 30-day all-cause mortality, permanent pacemaker implantation, ischaemic stroke, acute kidney injury, myocardial infarction, cardiogenic shock, major vascular complications, and major or life-threatening bleeding were evaluated. Five-year outcomes included all-cause mortality, ischaemic stroke, myocardial infarction and all-cause hospitalization. Cox regression was used to estimate hazard ratios (HRs) with 95% CIs. Results A total of 1414 RA+ (4.3%) and 39 004 RA− participants were eligible. After matching, 1374 were included in each cohort. At 30 days, outcomes did not differ between RA+ and RA− groups; mortality was 2.0% vs 1.5% (OR 1.29; 95% CI 0.73–2.29), with no significant differences in other endpoints. Over 5 years, mortality was 23.8% vs 20.5% (OR 1.12; 95% CI 0.97–1.31), and stroke, myocardial infarction and hospitalization were similar; HRs were concordant with OR estimates. In sex-based analyses of RA patients, outcomes did not differ by sex. Conclusion In this large observational study, TAVR was not associated with excess short- or long-term risk in patients with RA. These findings support TAVR as a safe therapeutic option in RA patients with aortic stenosis.