Citations

Abstract BACKGROUND We sought to characterize the cognitive profile among individuals with mild cognitive impairment with Lewy bodies (MCI‐LB) to help guide future clinical criteria. METHODS Systematic review and meta‐analysis included MCI‐LB studies with cognitive data from PubMed, Embase, Web of Science, and PsycINFO (January 1990 to March 2023). MCI‐LB scores were compared to controls, MCI due to Alzheimer's disease (MCI‐AD), and dementia with Lewy bodies (DLB) groups with random‐effects models. RESULTS We included 26 studies and 2823 participants. Across all domains, the MCI‐LB group performed worse than controls and better than DLB. Compared to MCI‐AD, the MCI‐LB group performed worse in attention/processing speed ( g = –0.24, 95% confidence interval [CI]: –0.35, –0.12), attention/executive ( g = –0.42, 95% CI: –0.56, –0.28); better in verbal immediate recall ( g = 0.37; 95% CI: 0.15, 0.59) and delayed memory ( g = 0.40; 95% CI: 0.22, 0.58). DISCUSSION The cognitive profiles in MCI‐LB and MCI‐AD are consistent with established profiles in DLB and AD. Neuropsychological assessment may be helpful in differential diagnosis, even in early disease states. Highlights We performed a systematic review and meta‐analysis for cognition in mild cognitive impairment with Lewy bodies (MCI‐LB). Compared to MCI due to Alzheimer's disease (MCI‐AD), MCI‐LB had worse attention, executive function, and processing speed. Compared to MCI‐AD, MCI‐LB had better verbal immediate and delayed recall. The MCI‐LB group was worse on all cognitive domains than controls, and better than dementia with Lewy bodies. Studies used different tests and there is a need for global efforts for harmonization.

Background The aim of this study was to examine the potential added value of including neuropsychiatric symptoms (NPS) in machine learning (ML) models, along with demographic features and Alzheimer's disease (AD) biomarkers, to predict decline or non-decline in global and domain-specific cognitive scores among community-dwelling older adults. Objective To evaluate the impact of adding NPS to AD biomarkers on ML model accuracy in predicting cognitive decline among older adults. Methods The study was conducted in the setting of the Mayo Clinic Study of Aging, including participants aged ≥ 50 years with information on demographics (i.e., age, sex, education), NPS (i.e., Neuropsychiatric Inventory Questionnaire; Beck Depression and Anxiety Inventories), at least one AD biomarker (i.e., plasma-, neuroimaging- and/or cerebrospinal fluid [CSF]-derived), and at least 2 repeated neuropsychological assessments. We trained and tested ML models using a stepwise feature addition approach to predict decline versus non-decline in global and domain-specific (i.e., memory, language, visuospatial, and attention/executive function) cognitive scores. Results ML models had better performance when NPS were included along with a) neuroimaging biomarkers for predicting decline in global cognition, as well as language and visuospatial skills; b) plasma-derived biomarkers for predicting decline in visuospatial skills; and c) CSF-derived biomarkers for predicting decline in attention/executive function, language, and memory. Conclusions NPS, added to ML models including demographic and AD biomarker data, improves prediction of downward trajectories in global and domain-specific cognitive scores among community-dwelling older adults, albeit effect sizes are small. These preliminary findings need to be confirmed by future cohort studies.

Summary Integrins are heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1 is a key mediator of angiogenesis and its dysregulation is associated with tumor progression and metastasis. Despite numerous efforts, α5β1-targeting therapeutics have been unsuccessful due to poor efficacy and off-target effects. A contributing factor is our limited understanding of how integrin conformation influences interactions with therapeutics. Using cell-based functional assays, patient-derived xenografts, biophysics, and electron microscopy, we shed light on these relationships by characterizing two anti-α5β1 antibodies, BIIG2 and MINT1526A. We show that both antibodies bind α5β1 with nanomolar affinity, reduce tube formation in vitro , and bind overlapping epitopes that block fibronectin binding. However, using electron microscopy, we reveal that while BIIG2 binding does not substantially alter the conformational states, MINT1526A preferentially recognizes the bent conformation and restricts the conformational ensemble. These insights can guide which aspects to prioritize to improve the design of future integrin-targeted therapeutics.

Abstract To assess breast imaging fellowship program directors’ perspectives of the outcomes of the first-ever virtual interview season. A 19-question survey was constructed by members of the Fellowship Match Committee of the Society of Breast Imaging and distributed via email to 103 program directors. An initial email with a link to the survey was distributed on May 17, 2023, with 2 reminder emails sent on May 31, 2023, and June 20, 2023. The survey was closed on June 26, 2023. Results were compiled, and a descriptive statistical analysis was performed using Excel. There were 36 total responses yielding a response rate of 35% (36/103). The majority of programs, 61% (22/36), did not fill positions with any internal candidates. Overall, 72% answered that the perception of their fellow’s performance was equal to or higher than those in prior years. Despite the effects of the pandemic on clinical exposure for this cohort, 73% of programs stated that the fellow’s foundational knowledge was equivalent or better. Remarkably, 81% of respondents stated that procedural skills were equivalent or better, and 78% stated that communication skills were equivalent or better. This is the first study to investigate the outcomes of the unexpected pivot to virtual interviews. Despite the lack of preparation for this operational shift, it does not appear to have negatively impacted the program directors’ impressions of their matched fellows.

Abstract Background Perry syndrome (PS) is a rare and fatal hereditary autosomal dominant neurodegenerative disorder caused by mutations in dynactin ( DCTN1 ). PS brains accumulate inclusions positive for ubiquitin, transactive‐response DNA‐binding protein of 43 kDa (TDP‐43), and to a lesser extent dynactin. Objectives Little is known regarding the contributions of TDP‐43, an RNA binding protein that represses cryptic exon inclusion, in PS. Therefore, we sought to identify the degree of TDP‐43 dysfunction in two regions of PS brains. Methods We evaluated the levels of insoluble pTDP‐43 and TDP‐43‐regulated cryptic RNAs and protein in the caudate nucleus and substantia nigra of 7 PS cases, 12 cases of frontotemporal lobar degeneration (FTLD) with TDP‐43 pathology, and 11 cognitively healthy controls without TDP‐43 pathology. Results Insoluble pTDP‐43 protein levels were detected in PS brains to a similar extent in the caudate nucleus and substantia nigra but lower than those in FTLD brains. The caudate nucleus of PS showed accumulation of eight TDP‐43‐regulated cryptic RNAs ( ACTL6B , CAMK2B , STMN2 , UNC13A , KCNQ2 , ATG4B , GPSM2 , and HDGFL2 ) and cryptic protein (HDGFL2) characteristic of FTLD. Conversely, only one cryptic target, UNC13A , reached significance in the substantia nigra despite similar pTDP‐43 levels. Conclusion We detected TDP‐43 cryptic RNAs and protein in PS caudate nucleus. Given the importance of cryptic exon biology in the development of biomarkers, and the identification of novel targets for therapeutic intervention, it is imperative we understand the consequences of TDP‐43 dysfunction across different brain regions and determine the targets that are specific and common to TDP‐43 proteinopathies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objectives: ImPACTS (Improving Acute Care Through Simulation) is a collaborative simulation-based program partnering pediatric specialty centers (“hubs”) with general emergency departments (GEDs) to improve pediatric acute care. Objective measurements of ImPACTS, such as evaluating Pediatric Readiness Score (PRS) and simulation-based outcome improvements, have been reported previously. Barriers to and facilitators of program involvement and the downstream effects of the program have not been previously described. This study explores these aspects and key drivers for successful collaboration. Methods: The authors performed open coding of semistructured interviews of hub team members and pediatric emergency care coordinators (PECCs) from community GED “spokes.” We then identified and explored themes within the categories of barriers to, facilitators of, and barrier mitigation strategies for successful partnerships from the perspectives of both groups. Results: Analysis generated 4 dominant themes: buy-in, communication, personnel, and logistics. Engagement, institutional support, and buy-in of site leaders and individual participants were crucial to successful implementation, without which the programs were not completed or never started. Hubs benefited from project involvement via increased local engagement in pediatric readiness, organizational support, and further buy-in from institutional leadership, allowing for the future continuation of ImPACTS and similar programs. Benefits experienced by GEDs impacted education, pediatric readiness, and clinical and financial partnerships across institutions. Additionally, spoke interviewees cited downstream effects of participation, including increased collaboration and improved relationships with hub sites as being the most impactful. Conclusion: Understanding the key drivers of all collaborators is instrumental in successfully implementing large-scale educational and quality initiatives like the ImPACTS program.

Background: Non-ischemic cardiomyopathies can be primary (p-NICM) which involves mainly the heart muscle or caused by systemic disease with heart muscle involvement as it is seen in systemic infiltrative diseases (i-NICM). There is limited data on the safety and in-hospital outcomes of ventricular tachycardia (VT) ablation in i-NICM. Methods: We identified patients who underwent VT ablation between 2018-2021 using the National Inpatient Sample Database. i-NICM include amyloidosis, hemochromatosis, or sarcoidosis. In-hospital complications include mortality, acute kidney injury (AKI), acute heart failure (AHF), bleeding, vasopressor use, blood transfusion and cardiac tamponade. Multivariate logistic regression analyses were performed. Results : There were 7,420 VT ablations, 7,235 had P-NICM and 185 had i-NICM. A multivariable analysis did not reveal any difference in mortality (adjusted odds ratio [aOR]: 0.81; 95% confidence interval 0.32-1.98; p=0.62), AHF aOR: 0.88 (0.41-1.81; p=0.69, AKI aOR:1.17 (0.83-1.65); p=0.36, blood transfusion aOR: 0.63 (0.25-1.59); p=0.33, vasopressor aOR: 0.86( 0.51-1.49); p=0.61 or pericardial effusion/ tamponade aOR: 1.16 (0.67-2.1); p=0.58 Figure Conclusion: Patients with i-NICM had similar in-hospital complications compared to P-NICM further supporting the safety of VT ablation in managing recurrent VT in patients with i-NICM.

ImportanceAtrial fibrillation (AF) is the most common, chronic, cardiac arrythmia in older US adults. It is not known whether AF is independently associated with increased risk of retinal stroke (central retinal artery occlusion), a subtype of ischemic stroke that causes severely disabling visual loss in most cases and is a harbinger of further vascular events.ObjectiveTo determine whether there is an association between AF and retinal stroke.Design, Setting, and ParticipantsThis retrospective cohort study was performed between July 2023 and May 2024 using computerized inpatient, outpatient, emergency department, and skilled nursing facility claims files for a 5% sample of US fee-for-service Medicare beneficiaries aged 66 years and older between 2000 and 2020. Follow-up ended at death, conclusion of fee-for-service Medicare coverage, end of the study period, or loss to follow-up of 85% of the study cohort.ExposureAF, based on validated International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes.Main Outcomes and MeasuresThe primary end point was incident retinal stroke in the primary diagnostic position of a single claim in any venue of care. Secondary end points included retinal stroke in any position of a single claim, 1 positive control end point (cerebral ischemic stroke), and 4 negative control end points (central retinal vein occlusion, urinary tract infection, humeral fracture, and cataract). Unadjusted and adjusted hazard ratios (HRs) and rate differences were computed across matched and overlap-weighted cohorts with and without AF (defined as 1 inpatient claim or 2 outpatient claims within a 365-day period).ResultsIn total, 1 090 144 patients (591 400 female [54.3%]; mean [SD] age, 76.92 [7.09] years) were included in the study; 545 072 patients had AF and 545 072 were matched controls. The median (IQR) follow-up was 45 (18 to 90) months. In total, 1333 patients with AF (rate, 0.55 per 1000 person-years) and 1082 AF-free matched controls (rate, 0.50 per 1000 person-years) experienced retinal stroke. The cause-specific, adjusted HR of retinal stroke after overlap weighting was 1.14 (95% CI, 1.02 to 1.28; adjusted rate difference, 0.05 [95% CI, −0.01 to 0.11]). AF was associated with cerebral ischemic stroke (adjusted HR, 1.73 [95% CI, 1.69 to 1.76]; adjusted rate difference, 10.11 [95% CI, 9.72 to 10.49]). Of 4 prespecified negative control end points, AF was not associated with central retinal vein occlusion but was associated with urinary tract infection, cataract, and humeral fracture.Conclusions and RelevanceIn this cohort study of Medicare beneficiaries aged 66 years and older, AF was independently associated with retinal stroke. The magnitude of the association was small, and a contribution from residual, unmeasured confounding could not be excluded.