Citations

BACKGROUND: Myocardial flow reserve (MFR), measured by positron emission tomography (PET) myocardial perfusion imaging, provides valuable information on epicardial coronary disease, diffuse atherosclerosis, and microvascular function. Despite its routine use, the prognostic efficacy of 13 N-ammonia PET MFR remains unconfirmed in larger multicenter cohorts of patients with suspected or known coronary artery disease. METHODS: We considered patients from 5 sites in the REFINE PET (Registry of Flow and Perfusion Imaging for Artificial Intelligence with PET) registry who underwent 13 N-ammonia PET myocardial perfusion imaging for coronary artery disease. Clinical and imaging data were collected at the time of myocardial perfusion imaging. MFR was quantified as the ratio of stress to rest myocardial blood flow, using QPET software (Cedars-Sinai Medical Center, Los Angeles, CA). The primary outcome was all-cause mortality. Survival analyses were performed using Kaplan-Meier and Cox regression models adjusted for clinical and imaging covariates. RESULTS: In total, 6277 patients were included (median age of 65 years, 56% male). Median follow-up time was 3.8 years. There were 1895 patients with MFR ≤2 and 4382 with MFR >2. Patients with MFR ≤2 had significantly higher mortality than those with MFR >2 (n=701 [37.0%] versus n=537 [12.3%], respectively; P <0.001). Annualized all-cause mortality rates by MFR and summed stress score ranged from 1.7 to 15.8. In multivariable analysis, MFR ≤2 was independently associated with increased all-cause mortality in the overall population (hazard ratio, 2.70 [95% CI, 2.41–3.03]; P <0.001), even among patients with no perfusion defects (hazard ratio, 2.36 [95% CI, 1.93–2.89]; P <0.001). Mortality risk decreased across increasing MFR deciles, ranging from hazard ratio, 2.73 (95% CI, 2.39–3.11) to hazard ratio, 0.35 (95% CI, 0.25–0.49). CONCLUSIONS: In this large multicenter cohort, MFR derived from 13 N-ammonia PET myocardial perfusion imaging is a strong, independent predictor of all-cause mortality, even in patients with normal perfusion. An MFR of ≤2 identifies elevated risk, while higher values are associated with improved survival. These findings support the routine integration of MFR to enhance risk stratification in patients with suspected or known coronary artery disease.

Objective Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f‐FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f‐FTLD. We used a Bayesian linear mixed‐effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia. Methods Participants included 234 asymptomatic or prodromal carriers of C9orf72 , GRN , or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1‐weighted scans. The BLME models established individual voxel‐wise gray matter trajectories using the first 2 scans. Person‐specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time‐varying Cox proportional hazard models covarying for age. Receiver‐operating characteristic (ROC) curves estimated utility of cluster volume in discriminating which participants converted to dementia within 24 months. Results The BLME cluster volume predicted conversion to dementia in f‐FTLD mutation carriers overall and separately in C9orf72 , GRN , and MAPT , with comparable hazard ratios observed for atrophy W‐maps and regional volumes. Within a 24‐month timeframe, BLME cluster volume discriminated dementia converters from non‐converters with larger areas under the curve (AUCs) than other approaches. Interpretation Bayesian‐modeled individualized atrophy scores predict dementia progression among asymptomatic f‐FTLD mutation carriers and may have increased utility compared with other structural imaging methods when studying individuals over shorter timeframes that align with clinical trial design. ANN NEUROL 20269999:n/a–n/a

Objective: Patent foramen ovale (PFO) closure is recommended for patients younger than 60 years with embolic stroke of undetermined source (ESUS) or cryptogenic stroke, but it’s role in patients older than 60 years remains unclear. We aim to investigate the benefit of closure in patients older than 60 with ESUS or cryptogenic stroke. Methods: Patients older than 60 years with ESUS or cryptogenic stroke from several large tertiary hospitals were recruited, who received a PFO closure after multidisciplinary brain-heart case conference, compared to age-matched cohort patients with ESUS or cryptogenic stroke. The primary outcome included recurrent ischemic stroke that occurred up to a median follow up of 5 years following PFO closure between two groups. The safety outcome was the occurrence of any complications after PFO closure, including new onset atrial fibrillation (AF). Results: A total of 102 patients (Table 1) were included (mean age 66±4), 56 male (55%), who received a PFO closure. Procedure-related complications, including new onset transient AF were low (1%). After following patients up to 5 years, patients with PFO closure demonstrated a relatively low incidence of recurrent ischemic stroke (3.9%, 4/102), compared to age-matched control cohort with a total of 97 patients (mean age 67±4), which had higher incidence of stroke recurrency (8.2%, 8/97) (Table 2). Kaplan-Meier event curve (Figure 1) reveals a trend of reducing recurrent stroke in patients with PFO closure but not achieved statistical significance. Conclusions: In patients with cryptogenic stroke or ESUS who are older than 60 years, PFO closure demonstrated safety profiles with a noticeable trend of reducing recurrent ischemic stroke compared to their age-matched counterparts. Prospective randomized trials are warranted in this young-older population.

Background: Interfacility transfers, especially in rural settings, present challenges including limited ambulance availability, bed capacity, image sharing and disparities in access. Regional transfer minimizes time to definitive stroke center care, relies less on costly helicopter transport, supports local healthcare economies, and preserves comprehensive stroke center (CSC) resources for those most likely to benefit. Although these advantages are well-established and reflected in the guidelines, transfers within our connected care rural network were not previously accepted at hospitals outside of our central comprehensive stroke center (CSC). Methods: We identified a local primary stroke center to serve as the regional stroke transfer center (rSTC) within our larger telestroke network. Over one year, (2023-2024), stakeholder meetings with representatives from the rSTC, surrounding smaller hospitals and the CSC were conducted to pinpoint potential roadblocks and create workflows that facilitated regional transfer. Regionally appropriate transfers were defined as patients without LVO, low likelihood for any neurosurgical decompression, or critical illness requiring dedicated neuro-intensive care. Education surrounding these criteria occurred quarterly and case logs were maintained and reviewed by the rSTC stroke coordinator. Retrospective chart review one year following the intervention period (2024-2025) was performed. Results: Of the 99 total transferred patients, 73 (73.7%) patients were transferred regionally. Their average LOS was 2.1 days, with 0% mortality rate and 0% requiring a secondary transfer to the CSC. 26 (26.3%) patients went to the CSC; LOS was 10.6 days and mortality 23.1%. Transfer times were shorter for rSTC patients (60 min vs 188 min). Six CSC patients met regional criteria (26.3% overtriage rate). Conclusion: Establishing an effective regional transfer model is possible with broad stakeholder engagement and regular network maintenance. Following our intervention, most eligible patients remained local and were treated appropriately. Although there was a significant reduction of the patients transferred to the CSC, the majority of CSC transfers were also appropriately triaged. This rSTC model facilitates the care of all stroke patients by providing the right level of care for the right patient, avoiding futile transfers with costly admissions far from home while opening beds and reducing transfer times to CSCs.

Background: Timely and accurate triage of stroke patients in rural settings remains a critical challenge, especially for patients with large vessel occlusions (LVO) requiring rapid access to comprehensive stroke centers (CSCs). This project aimed to improve the efficiency and accuracy of transport decisions for EMS stroke care in rural Michigan by adapting American Heart Association (AHA) guidelines on prehospital management and EMS routing. Method: We established a novel database involving linking regional EMS records, regional hospital stroke code quality improvement data, and Get With The Guidelines–Stroke (GWTG-S) registry data for suspected and confirmed stroke cases originating from five counties within 60 minutes of an urban CSC in West Michigan. Using a stepped-wedge design, we adapted the model AHA Severity-Based Stroke Triage Algorithm and implemented it in four rural EMS agencies through a staged roll-out of educational programs delivered to EMS providers and regional ED staff. We analyzed pre- and post-intervention data to assess protocol compliance, bypass frequency, and time from EMS scene arrival to CT acquisition and reperfusion therapy delivery. Results: Among 949 (598 pre- and 351 post-intervention) stroke transports occurred between November 2021 to December 2024, guideline-compliant hospital destination selection improved from 62% to 71% (p=0.018). Stroke mimics saw the greatest improvement (72% to 88%, p<0.001) through reduced unnecessary bypass. LVO screening documentation increased (10% to 23%, p<0.001), and EMS scene arrival-to-CT time decreased by 7 minutes (95% CI: 3–11). Trends toward improved thrombolysis rates (18% to 26%, p=0.055) and faster EMS-to-needle times (99 to 87 min, p=0.059) were observed. Mechanical thrombectomy rates and transfer metrics remained unchanged. Conclusions: This project successfully implemented a rural stroke triage protocol aligned with AHA guidelines, improving EMS routing decisions and reducing time to imaging. The intervention enhanced access to thrombolysis, however did not expedite mechanical thrombectomy. Findings support the AHA protocol’s scalability and underscore the feasibility of rural stroke system optimization.

ABSTRACT Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) can reduce seizures in patients with drug-resistant epilepsy. However, seizure freedom is rare, and there is no early response biomarker to predict long-term seizure suppression. To evaluate a short-term biomarker of therapeutic response to DBS, we studied 18-minute trials of ANT stimulation in patients with drug-resistant epilepsy undergoing intracranial electroencephalography. We compared a standard high-frequency periodic versus a non-periodic pulse pattern. We found that short-term ANT stimulation within the clinically used amplitude range preferentially altered the first 150 ms of anterograde ANT to anterior cingulate and superior frontal connectivity. Non-periodic ANT stimulation selectively modified early cortico-cortical evoked potentials more than periodic stimulation, and these changes were driven by the response phase. These pattern-specific changes in connectivity between the ANT and spatially restricted cortical areas suggest differing mechanisms and are a promising biomarker for patients being treated with ANT-DBS.

Abstract Purpose Professional identities impact professional boundaries and hierarchies, influencing how physicians approach collaboration. Despite the growing emphasis on developing students to become effective collaborators, little is known about how other health professionals (OHPs) shape students' professional identity formation (PIF). This study explored how interacting with OHPs during clinical care contributed to medical students' construction of what it means to be a physician. Methods For this constructivist grounded theory study, researchers conducted 20 semi‐structured interviews with medical students during clinical clerkships. Students drew rich pictures representing their interactions with OHPs and described these pictures during their interviews. Interviews were iteratively conducted and analysed, enabling the research team to theorize how interacting with OHPs contributed to medical students' PIF. Results Participants expressed a strong desire to contribute to patient care and described how interprofessional interactions provided opportunities to do so in ways aligned with their current capabilities. These opportunities were often more accessible than the roles and responsibilities of physicians, and participating alongside OHPs fostered participants' sense of their own developing capabilities and belonging on healthcare teams. Interactions with OHPs helped participants to see the expertise of OHPs and the value of collaborating with them in ways that shifted their focus away from becoming independent. Conceptually, participants' interactions with OHPs became both a mirror reflecting their present readiness to meaningfully contribute and a prism through which they could envision their future identities as physicians in new ways. Conclusions Interprofessional interactions influenced medical students' current and future professional identities, enabling students to see themselves as contributors on health care teams and highlighting collaboration and interdependence as core attributes of the physician profession. These findings highlight opportunities to amplify the impact of interprofessional interactions on the PIF of medical students and the need for research into how OHPs view their roles in these processes.