Citations

Introduction: Advance care planning (ACP) supports goal-concordant care but remains underused nationally. In resident clinics, limited continuity, short visits, and lack of standardized workflows create barriers to ACP integration. In our Community Internal Medicine resident clinic, ACP discussion was documented in 2.5% of annual physicals, and 19.6% of paneled patients had an advance directive (AD) on file. We aimed to increase ACP documentation from 2.5% to 12.5% within 1 year without increasing perceived resident workflow burden. Methods: We conducted a resident-led quality improvement project using Lean Six Sigma methodology. Three interventions were implemented sequentially: nursing distribution of ACP brochures, an electronic medical record DotPhrase to prompt and document ACP discussions, and targeted patient portal outreach to patients without an AD before annual visits. The primary outcome was documented ACP discussion during annual physicals. Secondary outcomes included AD uploads and ACP consult referrals. The balancing measure was resident-perceived workflow burden. Charts were reviewed over 5-week periods at baseline (n = 118) and after each implementation phase (n = 132, 158, 129). Results: ACP documentation increased from 2.5% at baseline to 12.2%, 17.1%, and 24.0% across sequential phases (χ 2 (3) = 24.74, P < 0.0001). Pairwise comparisons versus baseline were significant (all P ≤ 0.005). AD upload rate increased from 1.7 to 6.0 per month, and ACP consult referrals increased from 0.0% to 10.9%. Mean perceived workflow burden decreased from 4.9 to 3.0. Conclusion: Workflow-embedded interventions improved ACP documentation, AD uploads, and ACP referrals without increasing perceived resident burden.

Brexucabtagene-autoleucel (brexu-cel) produces high rates of measurable residual disease-negative (MRD-) complete response (CR) in adults with Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL); however, subsequent relapses remain frequent. It is unclear whether maintenance with tyrosine kinase inhibitors (TKIs) can enhance remission durability. We evaluated outcomes among adults with relapsed/refractory Ph+ ALL who received commercial brexu-cel and achieved MRD- CR across 19 U.S. institutions. Considering TKI maintenance as a time-varying covariate, we analyzed outcomes based on receipt of subsequent TKI maintenance versus no maintenance. Patients receiving consolidative transplantation or non-TKI maintenance were excluded. Fifty-one patients were included: 20 received TKI maintenance and 31 received no maintenance. The use of TKI maintenance was associated with a significantly lower 1-year cumulative incidence of relapse (HR 0.12; 95% CI, 0.02-0.88; p=0.037) which translated into improved progression-free survival (PFS, HR 0.19; 95% CI, 0.04-0.85; p=0.029) and a trend towards improved overall survival (OS, HR 0.34; 95% CI, 0.07-1.62; p=0.18). There was no difference in non-relapse mortality (NRM, HR 0.83; 95% CI, 0.12-5.87; p=0.85). This real-world analysis supports the administration of TKI maintenance in Ph+ ALL following achievement of MRD- CR with brexu-cel as a strategy to improve PFS following chimeric antigen receptor T cell therapy.

Abstract Purpose: To explore the potential of the metaverse, a three-dimensional platform merging physical and virtual realities (VRs), in advancing the field of ophthalmology. This study examines its applications in areas such as VR-based surgical training, augmented reality (AR)-assisted surgeries, artificial intelligence (AI)-driven diagnostics, and teleophthalmology. This review builds upon previous literature by integrating recent evidence and technological advancements, offering a more comprehensive analysis of particular applications and barriers in ophthalmology. Methods: Academic literature published between 2019 and 2024 was identified through searches in the PubMed database and Google Scholar search engine using relevant keywords. This review focused on studies discussing the application of the metaverse in health care and ophthalmology, with particular attention to key trends, emerging uses, technological features, and associated challenges. Results: A total of 60 studies were deemed relevant for inclusion in this review. The infrastructure supporting the Metaverse comprises technologies such as the Internet of Things, digital twins, mirror worlds, nonfungible tokens, blockchain technology, and lifelogging. Together, these technologies create immersive environments that users can access through VR headsets, AR glasses, and handheld controllers. The metaverse presents promising opportunities in ophthalmology, particularly in enhancing clinical training through simulators such as the EyeSi™ surgical simulator, VRmagic EyeSi Slit Lamp, and the HelpMeSee™ VR simulator. In addition, it facilitates remote consultations and improves diagnostic and treatment options, exemplified by tools such as the Vivid Vision™ system for amblyopia, the Microsoft HoloLens™ for navigating complex anatomical structures, and AI-based platforms for the early detection of diseases such as glaucoma and diabetic retinopathy. Furthermore, the metaverse may enhance patient education by simulating the visual effects of ophthalmic conditions and visualizing postoperative outcomes. However, challenges, including financial limitations, data security concerns, and cultural acceptance, must be addressed. Conclusions: A gradual and context-specific integration of the metaverse is essential, particularly in underdeveloped regions. As the metaverse evolves, it holds significant potential to transform the field of ophthalmology by promoting global collaboration and innovation, complementing traditional practices, and ensuring equitable access to advanced healthcare solutions.

ABSTRACT Background Men with castration‐resistant prostate cancer (CRPC) who have a pre‐existing history of cardiovascular disease (CVD) or other comorbidities are often excluded from clinical trials involving oral androgen receptor pathway inhibitors (ARPi). In this study, we compared all‐cause and prostate cancer‐specific mortality among CRPC patients, with and without a pre‐existing history of CVD, receiving ARPi compared to chemotherapy. Methods Men with CRPC were identified using the Surveillance, Epidemiology, and End Results‐Medicare Linked Database from 2004 to 2015. Patients were grouped into two analytical cohorts by drug use. Inverse probability treatment weights (IPTW)‐adjusted Cox models and Fine‐Gray subdistribution hazards models were used to evaluate associations between ARPi and chemotherapy, and between ENZ and AA for all‐cause mortality and cancer‐specific mortality separately. Results The study cohort included 1438 men with CRPC. Nearly 54.4% of patients had a pre‐existing history of CVD. Patients with a pre‐existing history of CVD had a higher incidence of all‐cause and prostate cancer‐specific mortality compared to patients without a history of CVD (all‐cause mortality: 69.7% vs. 59.3%, prostate cancer‐specific mortality: 56.0% vs. 49.5%, respectively). In the pre‐existing history of CVD cohort, the IPTW‐adjusted Cox model showed a significantly lower all‐cause mortality in patients who received APRi, enzalutamide, and abiraterone, versus chemotherapy (IPTW‐adjusted hazard ratio [AHR], 0.56; 95% Confidence Interval [CI], 0.48–0.64; p ‐value < 0.001). Further, the IPTW‐adjusted competing risk model showed significantly lower prostate cancer‐specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW‐AHR, 0.48; 95% CI, 0.41 to 0.57; p ‐value < 0.001). In the without pre‐existing history of CVD cohort, the adjusted Cox model showed significantly lower all‐cause mortality in patients who received APRi than those who received chemotherapy (IPTW‐AHR, 0.49; 95% CI, 0.41–0.60; p ‐value < 0.001). Whereas the IPTW‐adjusted competing risk model showed significantly lower prostate cancer‐specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW‐AHR, 0.52; 95% CI, 0.42–0.64; p ‐value < 0.001). Conclusion In this population‐based cohort of older men with castration‐resistant prostate cancer, treatment with oral androgen receptor pathway inhibitors was associated with lower estimated risks of all‐cause and prostate cancer–specific mortality compared with chemotherapy in patients with and without pre‐existing CVD. These findings add real‐world comparative effectiveness evidence for patient populations not well represented in randomized clinical trials; however, given the observational design and limitations of administrative data, residual confounding and unmeasured clinical differences may have influenced the results.

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality. Accurate diagnosis of ischemia-causing coronary stenoses is essential for guiding revascularization and improving outcomes. Although invasive fractional flow reserve (FFR) remains the gold standard for functional lesion assessment, its use is limited by procedural invasiveness, cost, and complexity. CT-derived FFR (FFRct), based on computational fluid dynamics (CFD), was the first major advance in noninvasive physiological assessment, but its adoption has been hindered by intensive off-site computation and dependence on high-quality imaging. This review summarizes the evolution from invasive FFR to AI-driven functional assessment of coronary lesions. We examine the principles and validation of CFD-based FFRct and then focus on the shift toward artificial intelligence, including both machine learning (ML) and deep learning (DL) approaches. These methods range from models using engineered geometric and plaque features trained on large synthetic datasets to end-to-end systems that learn directly from imaging data. We discuss key validation studies evaluating diagnostic accuracy, prognostic value, and clinical utility, with attention to performance in challenging settings such as intermediate stenoses, heavy calcification, and patients with comorbidities. We also highlight major barriers to widespread adoption, including dependence on input data quality, limited explainability, regulatory hurdles, and integration into clinical workflows. Finally, we outline future directions, including AI-enabled virtual PCI planning, multimodal risk stratification, and broader access to functional cardiac assessment. AI has the potential to transform noninvasive coronary imaging by enabling a single CCTA scan to provide rapid, integrated evaluation of anatomy, plaque characteristics, and physiological significance, supporting more personalized care and better clinical outcomes.

Abstract Background Climate-related stressors such as heat, wildfires, and extreme weather are increasingly recognized as determinants of cardiovascular and oncologic health. However, their joint impact on overlapping cancer–cardiovascular disease (CVD) burdens remains unknown. We developed a Cardio-Oncology Burden Index (COBI) to quantify the co-prevalence of cancer and CVD at the community level and examined its association with climate vulnerability across U.S. census tracts. Methods We conducted a cross-sectional ecological analysis of 82,679 census tracts (328,683,841 residents) using the CDC PLACES database. COBI was derived using principal component analysis of age-adjusted prevalence of cancer, coronary artery disease, and stroke. The Climate Burden Index (CBI, 0–1 percentile) integrates multiple climate-related exposures, including extreme temperature, wildfire frequency, and severe weather events. Population-weighted mixed-effects regression models with county-level random effects estimated associations between CBI and COBI, adjusting for region, rurality, and environmental justice indicators. β coefficients represent percentage-point differences in COBI per unit (or category) increase in climate burden. Exposure–response relationships were examined using restricted cubic splines (RCS). Robustness was assessed via geographically matched (&lt;50 km) and fully matched (region, rural–urban commuting area, and environmental justice) analyses. Results Marked spatial heterogeneity was observed in both CBI and COBI across the U.S. (Fig. A–B). Higher climate burden was consistently associated with greater cardio-oncology burden (Fig. C), demonstrating a dose–response relationship: second vs lowest quartile β=0.92 (95% CI, 0.61–1.24); third vs lowest quartile β=1.61 (95% CI, 1.30–1.92); highest vs lowest quartile β=3.44 (95% CI, 3.11–3.76). The RCS model revealed a significant non-linear association (p_non-linear&lt;0.001), with a plateau at moderate exposures and a steep rise at the highest CBI levels (Fig. D). Results remained robust in sensitivity analyses (β=4.17 [95% CI, 3.62–4.71] for geographically matched; β=4.39 [95% CI, 4.10–4.69] for fully matched tracts; Table). Conclusions Greater climate burden is independently associated with higher cardio-oncology burden across U.S. communities, with disproportionate effects in the most climate-vulnerable areas. This novel, population-level linkage between climate stress and onco-cardiovascular disease burden, highlights an emerging syndemic at the intersection of environment, cancer, and CVD. Targeted mitigation and prevention strategies integrating environmental resilience into chronic disease prevention are urgently needed.For image description, please refer to the figure legend and surrounding text.

Background Although regional anesthesia (RA) is associated with improved pain control, reduced opioid use, and accelerated recovery after arthroplasty, racial and geographic differences have been identified in hip and knee arthroplasty, with limited data for shoulder and ankle arthroplasty. We examined differences in RA utilization for shoulder, hip, knee, and ankle arthroplasty, based on patient-level and hospital-level characteristics. Methods Using the National Inpatient Sample, we conducted a cross-sectional study of adults who underwent shoulder, hip, knee, and ankle arthroplasties from 2016 to 2020. RA was defined using procedure codes for neuraxial anesthesia and peripheral nerve blocks. Weighted descriptive statistics summarized RA utilization and compared patient-level and hospital-level characteristics using standardized mean differences (SMDs), with ≥0.10 indicating meaningful differences. Results We identified 1132 011 unweighted admissions, representing approximately 5.7 million weighted arthroplasties. RA was used in 7.0% of cases. RA utilization varied by procedure type, with the highest rates in shoulder (11.4%) and ankle arthroplasty (11.4%), followed by knee (9.1%) and hip arthroplasty (2.4%). Variation in RA utilization was observed in ankle arthroplasty based on race (SMD=0.11) and primary payer (SMD=0.12). RA use also varied by hospital size for shoulder (SMD=0.13), hip (SMD=0.29), and knee arthroplasty (SMD=0.22), by hospital location and teaching status for shoulder (SMD=0.17), hip (SMD=0.18), knee (SMD=0.19), and ankle arthroplasty (SMD=0.12), and by geographic region for shoulder (SMD=0.26), hip (SMD=0.45), knee (SMD=0.24), and ankle arthroplasty (SMD=0.17). Conclusions There is notable variation in RA use for inpatient arthroplasty across hospitals and geographic regions, with limited variation based on patient characteristics. These findings highlight the presence of system-level variation in RA use and underscore the need for further research to better understand the drivers of these patterns.

Background: Resistant hypertension represents a significant clinical challenge, often driven by dysregulated aldosterone production. Aldosterone synthase inhibitors (ASIs) are a novel therapeutic class designed to directly suppress aldosterone biosynthesis. This study aimed to synthesize evidence regarding the comparative efficacy, optimal dosing, and dose–response relationships of three ASIs—baxdrostat, lorundrostat, and osilodrostat—for the treatment of resistant hypertension. Methods: A systematic review and network meta-analysis (NMA) were conducted following PRISMA 2020 guidelines. We searched PubMed, Web of Science, and CENTRAL for randomized controlled trials (RCTs) published up to 31 October 2025. The primary outcome was the mean change in systolic blood pressure (SBP) compared to placebo. We utilized a frequentist random-effects model, characterized dose–response relationships via meta-regression, and ranked treatments using the Surface Under the Cumulative Ranking Curve (SUCRA). Results: The analysis included 8 RCTs comprising 3253 participants. Baxdrostat 2 mg once daily demonstrated the greatest antihypertensive efficacy with a mean SBP reduction of −13.8 mmHg (95% CI: −17.5 to −10.1) versus placebo, followed by Lorundrostat 100 mg (−12.5 mmHg) and Baxdrostat 1 mg (−11.5 mmHg). SUCRA analysis identified Baxdrostat as the highest-ranked treatment (83.0%), followed by Lorundrostat (67.8%) and Osilodrostat (55.5%). Dose–response meta-regression revealed strong linear correlations for Baxdrostat (R2 = 0.91), Osilodrostat (R2 = 0.81), and Lorundrostat (R2 = 0.80). Conclusions: ASIs, particularly Baxdrostat and Lorundrostat, offer robust blood pressure reductions in patients with resistant hypertension. The strong linear dose–response relationships suggest these agents have a favorable therapeutic window for titration. While effective, clinical implementation requires careful monitoring for adverse events.