Publications by Year: 2026

IMPORTANCE: Management after an ischemic stroke occurring despite direct oral anticoagulant (DOAC) therapy for atrial fibrillation (AF) varies widely. Switching anticoagulation is common in clinical practice, although evidence supporting this strategy is limited.

OBJECTIVE: To evaluate whether continuation of treatment with the same DOAC was noninferior to switching oral anticoagulant therapy with respect to 90-day clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter registry-based cohort study with an emulated target trial design included consecutive adult patients with AF who experienced a breakthrough ischemic stroke while receiving uninterrupted DOAC therapy and resumed anticoagulation therapy thereafter. Patients were enrolled between February 2020 and February 2025, across 35 stroke centers in 9 countries in Europe and North Africa, with a standardized 90-day follow-up. The dataset was locked on September 1, 2025. A noninferiority comparison of switching vs continuation strategies was performed. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW). The primary noninferiority margin was an absolute risk difference of 3.0 percentage points in 90-day net clinical benefit.

EXPOSURE: The intervention group switched to treatment with a different DOAC or vitamin K antagonist; the comparator group continued therapy with the prestroke DOAC.

MAIN OUTCOMES AND MEASURES: The primary outcome was 90-day net clinical benefit, defined as recurrent ischemic stroke and moderate to severe bleeding. Secondary outcomes included recurrent ischemic events, symptomatic intracerebral hemorrhage, moderate to severe extracranial bleeding, all-cause mortality, and vascular death.

RESULTS: Among 1006 patients included in the analysis (median age, 80.4 [IQR, 73.4-85.4] years; 503 female [50.0%] and 503 [50.0%] male), 463 (46.0%) continued the same DOAC therapy and 543 (54.0%) switched therapy. After IPTW adjustment, the 90-day net clinical benefit was 4.9% with switching and 5.1% with continuation, corresponding to a risk difference of -0.3 percentage points (90% CI, -2.7 to 2.1 percentage points), meeting the prespecified noninferiority criterion. For recurrent ischemic events and bleeding outcomes, the absolute differences were within the predefined noninferiority margins. Noninferiority was not demonstrated for all-cause or vascular mortality.

CONCLUSIONS AND RELEVANCE: In patients with breakthrough ischemic stroke during DOAC therapy, switching anticoagulation treatment was not associated with clinically meaningful short-term benefit compared with continuation. These findings suggest that switching does not provide additional benefit compared with continuing treatment with the same DOAC. Randomized clinical trials are needed to identify strategies to improve secondary prevention after a breakthrough ischemic stroke.

PURPOSE: This study describes the patient-centered approach to hearing technology selection and fitting of the participants randomized to a best practice hearing intervention as part of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study (ClinicalTrials.gov identifier NCT03243422). We evaluated associations between hearing technology with daily hours of hearing aid use and listening and communication goal achievement.

METHOD: The ACHIEVE study (n = 977) was a multicenter, randomized controlled trial designed to test the effect of a best practice hearing intervention versus health education control on cognitive decline over 3 years among older adults with untreated hearing loss. Participants were aged 70-84 years, had adult-onset mild-to-moderate hearing loss, had no previous hearing aid use, and were without substantial cognitive impairment at baseline. Participants randomized to the hearing intervention (n = 490) received a patient-centered comprehensive hearing program including hearing aids with varying feature sets, characterized as standard, advanced, and premium technology levels, and offered at least one hearing-assistive technology (HAT). The Client-Oriented Scale of Improvement (COSI) was used to identify listening needs that guided intervention delivery and was used to assess attainment of hearing-related goals following  10-week intervention period. Hearing aid datalogging was used to measure hours of daily wear. We estimated the association between hearing aid technology level, HATs, hours of wear, and COSI goal attainment using an ordered logistic model adjusting for auditory and sociodemographic characteristics. Proportionality odds assumption was checked for all models.

RESULTS: A total of 459 participants completed the hearing intervention and reported outcomes. Selection of hearing aid technology level and HATs was guided through evidence-based protocol-directed recommendations, with 88 (19%) participants receiving standard; 260 (57%) participants, advanced; and 111 (24%) participants, premium hearing aid technology. Mean daily hours of hearing aid use was high (M = 9.3 hr across all participants) and did not differ between hearing technology (levels or HATs). Participant COSI goals, which included categories such as conversation in noise and in quiet or attending church and/or meetings, improved and were not dependent on technology used. Participants benefited from patient-centered hearing intervention, and there were no statistically significant associations among hearing aid technology level, HATs, hours of use, and change in COSI goals.

CONCLUSIONS: The patient-centered selection of hearing technology used in the ACHIEVE study resulted in high levels of hearing aid and HAT usage, along with positive COSI listening goal attainment for the majority of participants. Carefully assessed and selected technology is needed to meet individual auditory rehabilitation needs.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.32069253.

BACKGROUND: Cisplatin is broadly used, but it is nephrotoxic and ototoxic. No large-scale investigation has analysed cisplatin-related ototoxicity while considering quantified renal function, cumulative dose, comorbidities, and modifiable risk factors. Our aim was to fill this knowledge gap.

METHODS: The Platinum Study is a well-characterised multicentre cohort study of cisplatin-treated testicular cancer survivors enrolled 2012-18 in eight academic cancer centres in the USA, Canada, and the UK, with follow-up ongoing. Measures include audiometrically assessed hearing (0.25-12 kHz), real-world speech-in-noise perception, and hearing loss progression. Multivariable analyses evaluated associations of audiometrically-assessed hearing with estimated glomerular filtration rate (eGFR), comorbidities, health-behaviours, and cisplatin dose. Mediation analyses tested direct and indirect eGFR contributions to ototoxicity and eGFR-dose interactions.

FINDINGS: Among 1422 survivors (median age 38 years, IQR 31-47), ototoxicity affected 1061 (75%), and audiometrically-assessed hearing was significantly associated with cumulative cisplatin dose (β = 8.72 per 100 mg/m2, p = 0.0004), reduced eGFR (β = 3.90 per 20 mL/min/1.73 m2, p = 0.043), hypertension (β = 4.06, p = 0.0005), non-White race (β = 3.26, p = 0.014), physical inactivity (β = -0.24 per 1000 kCal/week, p = 0.034), and age (β = 5.21 per 5 years, p < 0.0001). Cisplatin dose significantly interacted with eGFR (p = 0.017); 7.2% (95% CI 0.9-18.8; p < 0.05) of cisplatin's ototoxicity was mediated through reduced eGFR and 5.6% (0.4-16.1; p < 0.05) through interaction effects. Poorer speech-in-noise perception was associated with cognitive dysfunction (β = 1.01, p = 0.026), hypercholesterolaemia without statin use (β = 0.71, p = 0.029), lower education (β = 0.91, p = 0.0098), and hearing loss severity (β = 0.08, p < 0.0001). Hearing loss progression was associated with age (β = 0.30, p < 0.0001), while statin use for hypercholesterolaemia was protective (β = -4.09, p = 0.0048).

INTERPRETATION: Cisplatin's dose-dependent ototoxicity is amplified by its nephrotoxicity, with the dose-response becoming stronger as eGFR worsens. Given age-related declines in both eGFR and hearing, follow-up of cisplatin-treated survivors should monitor both, and include strict control of cardiovascular risk factors. Statin use for hypercholesterolaemia appeared protective against hearing loss progression, suggesting a potential therapeutic intervention for reducing long-term auditory complications in this population.

FUNDING: The National Cancer Institute.

UNLABELLED: Ventral horn microglia in the spinal cord proliferate after nerve injuries and migrate towards the cell bodies of injured motoneurons surrounding them. However, the significance of microglia enwrapping axotomized motoneurons has remained unclear. Moreover, some injured motoneurons degenerate while others regenerate. In mice spinal cords we found that each motoneuron fate associates with microglia of different activation profiles. Microglia surrounding degenerating motoneurons form cell clusters that fully envelop the cell body and express high TREM2 and large CD68 granules, with female microglia expressing higher levels. Microglia surrounding motoneurons undergoing regeneration remain individualized and also upregulate TREM2 and CD68, but to a lesser extent than microglia around degenerating motoneurons. Removal of TREM2, either globally throughout development or specifically in microglia prior to nerve injuries, reduces p-SYK signaling and CD68 expression in all activated microglia, but more so inside microglia forming tight cell clusters around degenerating motoneurons. This effect is also larger in females. TREM2 absence did not prevent microglia clustering around degenerating motoneurons but prevented the loss of some small MNs. In addition, TREM2 depletion interfered with the retrograde cell body chromatolytic reaction that is characteristic of regenerating motoneurons and delayed muscle reinnervation. We conclude that within the same motor pools, TREM2 facilitates microglia removal of some degenerating motoneurons while it facilitates regeneration of other motoneurons. The signals that direct the development of these different microglia phenotypes over degenerating and regenerating motoneurons, as well as the mechanisms that induce degeneration in some motoneurons while most others regenerate, remain to be investigated.

SIGNIFICANCE STATEMENT: Microglia frequently enwrap neurons undergoing cellular stress being one example the microglia reaction around motoneurons axotomized after nerve injuries. The significance of this microglia-neuron relationship is unclear. We found that microglia surrounding axotomized motoneurons upregulate TREM2, but with differences depending on whether microglia associated with regenerative or degenerative motoneurons. Loss-of-function experiments showed that TREM2 promotes removal of some degenerating motoneurons while facilitates the regeneration of others. We conclude that microglia TREM2 serves a dual function depending on the motoneuron health state. This knowledge is critical for designing future therapies that aim to improve motoneuron regeneration or preservation by altering TREM2 function.

OBJECTIVES: Within the World Health Organization's International Classification of Functioning, Disability and Health, audiometric hearing loss and perceived hearing handicap are related but distinct. Family relational processes may buffer how sensory loss translates into lived burden via support, communication norms, and coping. We tested whether familism or family cohesion moderated the association between hearing loss and perceived handicap among Hispanic/Latino adults.

DESIGN: Cross-sectional analysis of the Hispanic Community Health Study/Study of Latinos and the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study (n = 4889). Hearing loss was defined as better-ear four-frequency pure-tone average (PTA) >25 dB HL. Perceived hearing handicap was measured with the 10-item Hearing Handicap Inventory for Adults/Elderly-Screening version (HHIA/E-S). Adjusted associations of hearing loss with perceived handicap were estimated by multivariable regression. Moderation was tested with continuous interaction terms for familism and family cohesion.

RESULTS: Participants with hearing loss had higher adjusted mean HHIA/E-S scores than those without (6.30 versus 2.91; Geometric Mean Ratio = 2.16, 116% higher; p < .001), indicating roughly double the perceived handicap among those with hearing loss. Although PTA was strongly related to handicap, variability in HHIA/E-S across the range of PTA continuum indicated incomplete correspondence between measures. Across all levels of familism and family cohesion, hearing loss was associated with approximately a two-fold higher perceived handicap (Geometric Mean Ratios ≈ 1.9 to 2.5). No consistent pattern of moderation by familism or family cohesion was noted.

CONCLUSIONS: Audiometric hearing loss was strongly associated with greater perceived handicap, and the magnitude of this association was similar across all levels of familism and family cohesion. Consistent with the World Health Organization's International Classification of Functioning, Disability and Health framework, audiometric thresholds and perceived impact only partially aligned in this cohort, and this relationship was not meaningfully altered by familism or family cohesion. Together, these findings underscore that audiometric thresholds alone do not fully capture the lived impact of hearing loss, as reflected by substantial variability in perceived handicap at similar levels of PTA, and highlight the importance of integrating self-reported experience with clinical history and patient context when identifying need and planning care.