Citations

Background: Patients with cardiac implantable electronic devices (CIEDs) undergoing radiation therapy face potential risks of device malfunction. Proton beam therapy (PBT), with its reduced neutron scatter, has emerged as a potentially safer alternative, yet real-world safety data remain scarce. Methods: We conducted a retrospective cohort study of 100 patients with CIEDs (76 pacemakers, 24 ICDs) who underwent PBT from 2016 to 2023 at a quaternary center. Baseline and serial device interrogations were performed before, during, and after treatment to assess lead impedance, capture thresholds, battery function, and arrhythmic events. Patients were stratified by pacemaker dependence and monitored accordingly. Primary outcomes included device malfunction and new-onset arrhythmias during treatment. Secondary outcomes included device parameter changes, one-year arrhythmia incidence, and cardiac-related hospitalizations. Results: No treatment-related deaths or major device failures occurred. Device malfunction was rare (2 pacemaker patients, 2.6%), with no malfunctions in ICD recipients. Transient, non-clinically significant changes in lead impedance and capture thresholds were observed. Arrhythmias during treatment occurred in 26% of pacemaker and 25% of ICD patients, but only 4% developed new arrhythmias. At one year, device-related complications and cardiac outcomes remained comparable across groups. Independent predictors of arrhythmias during treatment included a higher radiation dose per fraction (OR 1.45; p=0.001), a longer treatment duration (OR 1.12; p=0.04), and a higher number of fractions (OR 1.20; p=0.01). Conclusion: Proton beam therapy appears safe in patients with CIEDs, with a low incidence of clinically significant device malfunctions or arrhythmias. These findings support the integration of PBT into routine practice for this population and underscore the importance of structured monitoring protocols and prospective guideline refinement.

Abstract Background In the current clinical workflow of radiation oncology, therapists manually summarize the physician‐issued Computed Tomography (CT) simulation orders to prepare patients' CT simulations. This process increases the workload, introduces variability in documentation quality, and is prone to human errors. Purpose This study aims to address these challenges using a large language model (LLM) to automate the generation of summaries from the CT simulation orders and evaluate its performance. Methods A total of 607 CT simulation orders were collected from the Aria database at our institution. A locally hosted LLaMa 3.1 405B model, accessed via the Application Programming Interface (API) service, was used to extract keywords from the CT simulation orders and generate summaries. The downloaded CT simulation orders were categorized into seven groups based on treatment modalities and disease sites. For each group, a customized instruction prompt was developed collaboratively with therapists to guide the LLaMa 3.1 405B model in generating summaries. The ground truth for the corresponding summaries was manually derived by carefully reviewing each CT simulation order and subsequently verified by therapists. The accuracy of the LLM‐generated summaries was evaluated by therapists using the ground truth. Results Over 98% of the LLM‐generated summaries aligned with the ground truth in terms of accuracy. Our evaluations showed an improved consistency in format and enhanced readability from the LLM‐generated summaries compared to the corresponding therapist‐generated summaries. This automated approach demonstrated consistent performance across all groups, regardless of treatment modality or disease site. Conclusions This study demonstrated the high precision and consistency of the LLaMa 3.1 405B model in extracting keywords and summarizing CT simulation orders, suggesting that LLMs have great potential to assist in this task, reduce the workload of CT simulation therapists and improve radiation oncology workflow efficiency.

ABSTRACT As artificial intelligence (AI) continues to rapidly reshape health care, there is a critical need for clear frameworks for clinicians to ensure ethical, equitable, and effective integration and use of AI in patient care. Key integrations of AI include enhancing health communications, patient engagement, clinicians' training, pharmaceutical advertising, clinical decision‐making, and automation of clinical operations and workflow. However, there are growing concerns related to regulatory gaps, the spread of misinformation, security threats, patient and data privacy leaks, and widening health disparities gaps. These concerns are exacerbated by limited institutional infrastructure and limited AI literacy of clinicians and patients. Recent policy developments reflect efforts to guide responsible AI development and use. While progress has been made, the lack of standardized human oversight remains a critical gap, particularly as policies may not fully consider the challenges and complexities at institutional, societal, technical, and individual levels. Thus, herein, the Drug Information Practice and Research Network (DI PRN) of the American College of Clinical Pharmacy (ACCP) : (1) explores current and emerging multifaceted challenges, a call to action, and opportunities of AI integration in health care including examination of the regulatory, ethical, operational, and health equity implications; and (2) provides practical recommendations for responsible use of AI through DI PRN‐developed example case‐based approaches and best practices infographics to enhance AI literacy for diverse learners including clinicians, trainees, and patients. This DI PRN opinion paper highlights the importance of proactive governance frameworks and equips and empowers diverse learners with practical AI literacy tools to confidently engage with AI technologies in patient care.

BACKGROUND: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion—specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume—were associated with recurrent ischemic stroke within 90 days. METHODS: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%–99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T max (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome ( P <0.1). RESULTS: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02–1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03–3.28]). CONCLUSIONS: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.

Background: In younger patients (<60 years) with cryptogenic stroke (CS) presumed to be patent foramen ovale (PFO)-related, the standard approach involves transcatheter PFO closure combined with antithrombotic therapy. However, due to their exclusion from randomized clinical trials (RCTs), no formal recommendations exist for patients ⩾60 years. This study had two objectives (1) to compare the efficacy and safety of PFO closure versus antithrombotic therapy alone (ATA) exclusively in older patients (⩾60 years) and (2) to assess the outcomes of PFO closure in patients ⩾ 60 years versus < 60 years. Methods: We searched PubMed, Embase, Web of Science, and ScienceDirect databases to obtain articles in all languages from January 2004 until July 2025. The primary outcome was risk of recurrent stroke during follow-up. Secondary outcomes were risk of new-onset atrial fibrillation (AF), all-cause mortality, and in-hospital complications. PROSPERO registration ID: CRD420250652870. Results: Only one RCT (post hoc evaluation of the DEFENSE-PFO trial) and 11 observational studies were included. In patients aged ⩾ 60 years, risk of recurrent stroke was lower when PFO was closed compared with ATA (5.48% vs 10.05%, respectively, hazard ratio (HR) = 0.56, 95% confidence interval (CI) = 0.45–0.80, p < 0.001, I 2 = 45.6%). All-cause mortality was also lower for PFO closure versus ATA (1.73% vs 7.59%, respectively, HR = 0.41; 95% CI = 0.19–0.90, p = 0.02; I 2 = 43.8%). There was no difference between PFO closure and ATA in risk of new-onset AF (HR = 1.13, 95% CI = 0.53–2.44, p = 0.74). Compared with patients < 60 years, individuals ⩾ 60 years who underwent PFO closure had a higher risk of recurrent stroke (2.94% vs 1.04%, respectively, HR = 3.47; 95% CI = 1.61–7.48; p = 0.001), new-onset AF (4.86% vs 1.01%, respectively, HR = 4.12; 95% CI = 1.90–8.95; p < 0.001), and all-cause mortality during follow-up (8.32% vs 0.39%, respectively, HR = 8.24; 95% CI = 3.49–19.46; p < 0.0001). In-hospital complications after PFO closure were comparable between two age groups. Due to insufficient data, we were not able to perform a subgroup analysis based on anatomic features of PFO, antithrombotic regimen, or occluder devices. Conclusion: Based on available data, which is predominantly derived from observational studies, PFO closure is associated with a reduced risk of recurrent stroke compared to ATA in patients over 60 years. However, these findings are subjected to limitations, including the potential for selection bias, unmeasured confounding, and insufficient long-term follow-up. Furthermore, long-term randomized trials are essential to definitively confirm efficacy and establish clinical guidelines for PFO closure in this older population.

Abstract Objective The objective of this study was to summarize the available evidence regarding the clinical value and trend over time of lumbar cerebrospinal fluid (CSF) opening pressure utilization to diagnose spontaneous intracranial hypotension (SIH). Background CSF opening pressure obtained via lumbar puncture is one of the diagnostic criteria for SIH based on the International Criteria for Headache Disorders, 3rd Edition (ICHD‐3), but it has questionable utility as an initial investigation for diagnosing SIH. Methods The authors performed a systematic literature review and meta‐analysis. PubMed/MEDLINE, Scopus, and Cochrane Library were searched from inception to October 2022. Original studies and case series in English reporting three or more patients with suspected or known SIH and CSF pressure measurement were included. Meta‐analyses and meta‐regression were used to calculate pooled estimates and examine the impact of age, sex, and publication year on outcomes, including CSF pressure < 60 mm CSF, orthostatic headache, and positive findings on brain magnetic resonance imaging (MRI), spinal imaging, and radionuclide studies. Results For every 1‐year increase in the year of publication, the odds of reporting low CSF pressure decreased by 6.20% (adjusted odds ratio [aOR] = 0.94, aOR 95% confidence interval [CI] = [0.90, 0.97], p = 0.001), the odds of reporting a positive brain MRI increased by 4.67% (aOR = 1.05, aOR 95% CI = [1.01, 1.09], p = 0.026), and the odds of reporting orthostatic headache increased by 9.13% (aOR = 1.09, aOR 95% CI = [1.03, 1.15], p = 0.002). Each 1% increase in the percentage of patients with orthostatic headache was associated with a 3.13% increase in the odds of low CSF pressure (aOR = 1.03, aOR 95% CI = [1.01, 1.05], p = 0.003). Similarly, as the percentage of patients with low CSF pressure increased by 1%, there was a 2.53% increase in the odds of orthostatic headache (aOR = 1.03, aOR 95% CI = [1.01, 1.04], p = 0.005). It was estimated that 31.9% of patients with SIH had normal opening pressure (95% CI = [24.0%, 40.8%], prediction interval = [5.0%, 80.5%]). Every 1% increase in the percentage of patients with positive brain MRI was associated with a 5.25% increase in the odds of positive spinal imaging (aOR = 1.05, aOR 95% CI = [1.00, 1.11], p = 0.047). Age and positive radionuclide study did not significantly impact the outcomes measured. The corresponding I 2 for each outcome was reduced by controlling for study‐wide covariates believed to impact the prevalence of each outcome. Sensitivity analyses did not reveal discrepancies in results when studies requiring outcomes of interest were removed. Conclusion Our analysis found that recent studies indicate a reduced reliance on opening pressure for diagnosing SIH. Rather, results suggest an increasing reliance on contrast‐enhanced brain MRI, spine imaging, and clinical features for SIH diagnosis.

Importance An estimated 70% to 80% of older adults develop delirium in the intensive care unit (ICU). Objective To determine if a slow-tempo music (60-80 beats/min) listening intervention decreases delirium duration, delirium severity, pain, or anxiety in older adults undergoing mechanical ventilation. Design, Setting, and Participants This multicenter randomized clinical trial with concealed outcomes assessments was conducted in older adults undergoing mechanical ventilation from February 2020 to December 2023. Patients were enrolled from the ICUs of 2 hospitals affiliated with the Indiana University School of Medicine and from the Mayo Clinic in Rochester, Minnesota. Intervention A music intervention comprising classical and contemporary tracks, delivered twice daily through noise-canceling headphones and tablets for up to 7 days, was compared to active control listening to a silence track delivered under identical conditions. Main Outcomes and Measures The primary outcome was delirium/coma-free days during the 7-day intervention period assessed by the Confusion Assessment Method for the ICU (CAM-ICU) and the Richmond Agitation-Sedation Scale. The secondary outcomes were delirium severity assessed by the CAM-ICU-7, pain assessed by the Critical Care Pain Observation Tool, and anxiety assessed by the visual analog scale for anxiety (VAS-A). Results A total of 158 patients were randomized (mean [SD] age, 68 (9.2) years; 72 [45.5%] female and 86 [54.4%] male). In an intention-to-treat analysis, no differences were found in the number of delirium/coma-free days in the music intervention group compared with control (median [IQR] days, 2.5 [0-5] vs 3 [0-5]; P = .66). There were also no statistically significant differences in the mean CAM-ICU-7 scores, mean pain scores, or mean VAS-A scores over the 7-day intervention period. By end of the 7-day period, both music intervention and control groups had similar mean (SD) CAM-ICU-7 scores (2.72 [2.80] vs 2.56 [2.72]), Critical Care Pain Observation Tool scores (0.20 [0.55] vs 0.61 [1.29]), and VAS-A scores (43.6 [24.7] vs 28.8 [38.4]). Conclusions and Relevance In this randomized clinical trial among older adults undergoing mechanical ventilation, a slow-tempo music intervention did not demonstrate a statistically significant decrease in delirium duration, delirium severity, pain, or anxiety symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT04182334

Abstract Rehabilitation after musculoskeletal trauma is globally acknowledged as essential for restoring function and improving quality of life; however, significant variation exists in rehabilitation frameworks and services worldwide. Although certain principles—such as early intervention, structured care pathways, and multidisciplinary approaches—are universally recognized as important determinants of outcomes in trauma patients, their implementation and effectiveness vary considerably due to differences in health care infrastructure, economic resources, policy frameworks, and cultural contexts. Drawing on comparative analyses of rehabilitation frameworks across regions, including North America, Latin America, Europe, Asia-Pacific, and Africa, this paper identifies structural variations, systemic challenges, and innovations that can inform global rehabilitation efforts. Strategic international collaboration focusing on shared learning, standardized protocols, technology integration, and targeted investments is key to creating equitable and sustainable rehabilitation models, especially in resource-limited settings and aging populations.

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.