Citations

Abstract Background The increasing prevalence of dementia poses significant challenges for emergency department (ED) care, as persons living with dementia (PLWD) more frequently experience adverse outcomes such as delirium, prolonged stays, and higher mortality rates. Despite advancements in care strategies, a critical gap remains in understanding how ED interventions impact outcomes in this vulnerable population. This systematic review aims to identify evidence‐based ED care interventions tailored to PLWD to improve outcomes. Methods A systematic review was conducted in Ovid MEDLINE, Cochrane Library (Wiley), Scopus (Elsevier), and ProQuest Dissertations & Theses Global through September 2024. The review protocol was registered on PROSPERO (CRD42024586555). Eligible studies included randomized controlled trials, observational studies, and quality improvement initiatives focused on ED interventions for PLWD. Data extraction and quality assessment were performed independently by two reviewers, with disagreements resolved through discussion. Outcomes included patient satisfaction, ED revisits, functional decline, and mortality. Results From 3305 screened studies, six met the inclusion criteria. Interventions included nonpharmacologic therapies (e.g., music and light therapy), specialized geriatric ED units, and assessment tools, such as for pain. Tailored interventions including geriatric emergency units and community paramedic care transitions were effective in reducing 30‐day ED revisits and hospitalizations. However, heterogeneity in study designs and outcomes precluded meta‐analysis. Risk of bias ranged from low to moderate. Conclusion This review underscores the urgent need for standardized and evidence‐based interventions in ED settings for PLWD. Approaches including multidisciplinary care models and nonpharmacologic therapies demonstrated potential for improving outcomes. Future research should prioritize consistent outcome measures, interdisciplinary collaboration, and person‐centered care strategies to enhance the quality and equity of ED services for PLWD.

PURPOSE Neoadjuvant immunotherapy (IO) has become the standard of care for early-stage triple-negative breast cancer (TNBC), but not yet for other subtypes. We previously developed a clinical-grade mRNA-based immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the response predictive subtypes. We report the performance of ImPrint in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+HER2–) patients from five IO arms. METHODS A total of 204 HR+HER2– (MammaPrint high-risk) patients from five IO arms (anti–PD-1, anti–PD-L1/poly [ADP-ribose] polymerase inhibitor combination, anti–PD-1/toll-like receptor 9 dual-IO combination, and anti–PD-1 ± lymphocyte activation gene 3 dual-IO combination) and 191 patients from the chemotherapy-only control arm were included in this analysis. Patients were classified as ImPrint+ (likely sensitive) versus ImPrint– (likely resistant), using pretreatment mRNA. Performance of ImPrint for predicting pathologic complete response (pCR) to IO-containing arms was characterized and compared with tumor grade (III), MammaPrint (ultra) High2 risk (MP2), and estrogen receptor (ER)-low (ER ≤ 10%). RESULTS Overall, the pCR rate across the five IO arms was 33%. 26% of HR+HER2– patients were ImPrint+, and pCR rates with IO were 75% in ImPrint+ versus 17% in ImPrint–, with the highest pCR rate >90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint–. Tumor grade (III), MP2, and ER-low showed pCR rates in IO of 45%, 56%, and 63%, respectively, with lower pCR odds ratios (OR < 7.5) compared with ImPrint (OR = 14.5). CONCLUSION Using an accurate selection strategy, HR+HER2– patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (ie, pCR rate >65%-70%). ImPrint, an Food and Drug Administration IDE-enabled assay, may represent a way to identify HR+HER2– patients for IO that best balances likely benefit versus risk of serious immune-related adverse events.

Abstract Background: Classic metaphyseal lesions (CMLs) are considered specific for child abuse, but the reliability of radiologists in distinguishing CMLs from metaphyseal variations is unclear. Objective: To evaluate whether radiologists can differentiate between CMLs and metaphyseal variations in the knees. Materials and Methods: We performed a retrospective review of distal femur and proximal tibia radiographs in children under two years of age who underwent skeletal surveys for suspected child abuse. The CML group included children diagnosed with abuse and reported CMLs. The metaphyseal variation group included children not diagnosed with abuse, with reported metaphyseal variations and either no fractures or an isolated skull fracture. Radiographs were trimmed to exclude other injuries. Four pediatric and four general radiologists reviewed anonymized studies and categorized each case as CML, metaphyseal variation, normal, or indeterminate, with confidence levels (high, moderate, low). We analyzed diagnoses with moderate or high confidence. Interobserver agreement was assessed using kappa statistics. Results: There were 48 children with CMLs (40 initial, 38 follow-up) and 27 with metaphyseal variations (20 initial, 12 follow-up). Metaphyseal fragmentation was the most common variation, identified in 259 of 356 femurs (72.8%) and 69 of 83 tibias (83.1%). Fragmentations were most frequently located in the posterior or medial metaphysis, or both, in 257 of 259 femurs (99.2%) (257/259) and 68 of 69 tibias (98.6%). In the CML group, 34 of 115 initial CML diagnoses (29.4%) were read on follow-up as either metaphyseal variation (n=17) or normal (n=17). In contrast, in the metaphyseal variation group, only one follow-up case was diagnosed as a CML; the remainder were diagnosed as metaphyseal variation (n=22) or normal (n=2). Diagnostic performance for CML demonstrated high specificity (90.7%) and positive predictive value (94.9%), with moderate accuracy (76.1%), sensitivity (70.2%), and negative predictive value (55.2%). Interobserver agreement was substantial, with a mean kappa of 0.61. Conclusion: Radiologists demonstrated substantial agreement and high specificity in distinguishing CMLs from metaphyseal variations. Metaphyseal fragmentation was the most common variation and was uncommonly diagnosed as CML on follow-up.

This review describes approaches for encapsulation of pluripotent stem cells, the biomaterials used, strategies for differentiation into hepatocytes and β cells, and the impact of microencapsulation on cellular therapy.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

Background and purpose New Zealand White Rabbits are a useful preclinical model for neurovascular research. Inducing right common carotid artery aneurysms in New Zealand White Rabbits gives researchers the ability to test neurovascular devices in vivo. This study takes advantage of archived angiograms to obtain vascular measurements of interest for future research in rabbit models. Methods Rabbit angiograms from endovascular studies conducted in-house between 2005 and 2024 were analyzed using ImageJ at points of interest along the thoracic and abdominal aorta. Using scale references, the diameters of various New Zealand White Rabbit (2.5–3.5 kg) arteries were measured for aneurysm models and controls. Anatomic vascular variations were categorized and recorded. Results Measurable artery diameters at 39 points of interest were recorded for 170 female New Zealand White Rabbits. Type 1 vascular anatomy was the most common rabbit aortic arch, characterizing 85% of identifiable rabbit anatomies in this study. Conclusion By making these measurements available, this study simplifies future neurovascular studies, allowing for vasculature to be selected by size depending on the application. Additionally, the study offers insight into the relationship between elastase-induced aneurysms and surrounding vasculature size and draws size comparisons between some key arteries of interest.

Objective To assess integration of a single-use robotic-assisted cochlear implant (RA-CI) electrode array insertion system into surgical workflows, identify potential challenges, and inform best practices. Study Design Survey. Setting Survey data from 16 surgeons across 10 US hospitals. Patients CI candidates 12 years and older with radiographically normal cochleae. Intervention CI surgery with single-use RA-CI insertion system during electrode array insertion. Main Outcome Measures Number of RA-CI to achieve proficiency, estimated additional time for RA-CI, and best practices to successfully incorporate the RA insertion system into CI surgery. Results A total of 121 RA-CI cases were performed. All surgeons completed the survey. Most surgeons (62.5%) reported they would feel comfortable using the device within five cases. Eight (50%) reported use of the RA system added 5 to 10 minutes to the case, and seven (44%) reported an added 10–15 minutes. Providing adequate incision size to secure the unit base superior to the temporal line and maximizing exposure of the facial recess were the most recommended best practices. Additional recommendations included pulling the receiver/stimulator forward within the pocket to facilitate a full electrode array insertion and considering drive head placement and mastoidectomy size to maximize overall visibility during electrode array insertion. Conclusions Proficiency with an RA electrode array insertion system during CI surgery can be achieved with minor adjustments to the surgical approach, within relatively few use cases (generally <5) and with minimal time addition (between 5 and 15 min). Training to specific best practices is important before initial clinical use.