Citations

Importance Timely identification of aortic stenosis (AS) is essential for appropriate clinical management, yet screening remains limited by dependence on comprehensive echocardiography and trained imaging personnel. Objective To develop and validate a deep learning algorithm for detection of moderate or greater AS and prospectively evaluate its performance using artificial intelligence (AI)–guided focused cardiac ultrasound (FoCUS) acquired by novice operators. Design, Setting, and Participants This diagnostic study included retrospective algorithm development and validation and prospective evaluation of AI-guided FoCUS across Mayo Clinic sites in the Midwest, Arizona, and Florida. The model was developed using 6753 patients and evaluated in internal validation (n = 852), internal test (n = 844), and validation (n = 1912) cohorts. Performance was assessed on FoCUS acquired by experienced sonographers (n = 602) and prospectively by novice operators (n = 1302). The retrospective model development and validation cohorts comprised studies performed from January 2005 through September 2022. Prospective study was conducted in 2 enrollment periods from June to August 2024 and from June to September 2025. Participants from both periods were combined to comprise the final prospective cohort. Exposure AI-guided FoCUS acquisition and automated deep learning–based assessment for detection of moderate or greater AS. Main Outcomes and Measures Detection of moderate or greater AS. Performance was assessed using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and positive predictive value. Results The model demonstrated excellent discrimination in the internal test cohort (AUROC, 0.99; 95% CI, 0.98-1.00) and geographically distinct validation cohorts in Arizona (AUROC, 0.99; 95% CI, 0.97-1.00) and Florida (AUROC, 0.99; 95% CI, 0.96-1.00). Among FoCUS examinations acquired by experienced sonographers, sensitivity was 95% (95% CI, 82-99) and specificity was 97% (95% CI, 95-98). In the prospective novice-operator cohort, 1258 of 1302 examinations (96.6%) were suitable for automated analysis. Sensitivity was 93% (95% CI, 82-99) and specificity was 96% (95% CI, 95-97). Expert review of AI-positive and uninterpretable examinations increased the positive predictive value from 49.4% to 91.1%, with sensitivity of 85.4%. Conclusions and Relevance A deep learning algorithm accurately detected moderate or greater AS across validation cohorts in this study. In prospective evaluation, novice operators were able to acquire AI-guided FoCUS examinations that enabled accurate detection of moderate or greater AS. These findings support a scalable strategy that may expand access to AS detection in settings with limited echocardiography resources.

Abstract Distal radius fracture (DRF) open reduction and internal fixation (ORIF) is a common procedure performed across inpatient and outpatient settings. This study compared postoperative complications and healthcare utilization between these settings using a large national claims database. Patients aged 18 years and older who underwent DRF ORIF were identified in the PearlDiver Mariner database using International Classification of Diseases and Current Procedural Terminology codes. Service location determined surgical setting. Patients with pathological fractures, malignancy, or polytrauma were excluded. Cohorts were propensity matched 1:1 based on age, sex, Charlson and Elixhauser comorbidity indices, and relevant comorbidities. The matched cohort included 9,697 inpatient and 9,697 outpatient DRF ORIF cases. Serious postoperative complications occurred in 16.8% of inpatient procedures versus 5.0% of outpatient procedures. Inpatient surgery was associated with higher odds of surgical site infection (OR 2.23, 95% CI: 1.78–2.79), wound dehiscence (OR 2.57, 95% CI: 1.07–6.17), and deep vein thrombosis (OR 7.75, 95% CI: 3.53–17.04). Inpatients also had greater odds of emergency department visits (OR 1.17, 95% CI: 1.05–1.31), readmissions (OR 3.64, 95% CI: 2.91–4.54), reoperations (OR 2.15, 95% CI: 1.70–2.73), and higher 90-day reimbursements. Inpatient DRF ORIF was associated with significantly higher complication rates and increased postoperative healthcare utilization compared with outpatient procedures, with the largest absolute differences seen in readmissions, reoperations, and 90-day reimbursements. These associations are unlikely to be causal, as inpatient admission typically reflects greater medical necessity and clinical complexity not fully captured by administrative data. Nonetheless, because admission status is readily available at the point of care, it may serve as a practical flag to identify patients who warrant closer post-discharge surveillance and individualized follow-up planning. III.

Abstract Background Synthetic control arms (SCAs) derived from historical trial data can complement randomized controlled trials (RCTs), particularly in oncology where feasibility, ethical, and cost constraints may limit conventional trial designs. However, their validity for overall survival (OS) remains uncertain. We evaluated the feasibility and limitations of constructing SCAs from the ARCAD metastatic colorectal cancer (mCRC) database across multiple treatment lines. Methods Seven landmark RCTs representing first-, second-, and third-line settings were selected. External control arms were constructed from ARCAD individual patient-level data using propensity score matching based on key clinical and biological variables from a validated ARCAD prognostic score, with adjustment for geographic region and time era when needed. A prespecified two-step benchmarking framework assessed: (1) control-arm OS reproducibility and (2) virtual trial comparisons between matched synthetic controls and original RCT experimental arms. Agreement was evaluated using hazard ratios (HRs) and Z-tests. Results A total of 28,022 patients met the inclusion criteria. ARCAD-derived SCAs were successfully constructed for all selected RCTs and closely reproduced control-arm OS. After matching, baseline characteristics were well balanced, with minimal differences between included and excluded patients. Virtual trials showed concordant treatment-effect estimates with the original RCTs, with a median absolute HR deviation of 0.05 and no significant differences by Z-tests (P>.05). Survival outcomes were consistently reproduced across treatment lines. Conclusion ARCAD-derived SCAs reliably reproduced control-arm OS and benchmark treatment-effect estimates from landmark RCTs in mCRC. Despite limitations related to residual confounding and missing data, this framework supports benchmarking, trial design, and exploratory analyses when conventional control arms are impractical.

Background New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency evaluation and treatment of patients on AAT who develop acute neurological symptoms. Methods The American Heart Association convened 75 multidisciplinary experts for the Amyloid‐Related Imaging Abnormalities Summit: Cardiovascular and Stroke Considerations for β‐Amyloid Immunotherapy in AD in July 2025. These experts were divided into 8 work groups to evaluate the current evidence related to AAT usage in patients with cardiovascular risk factors and conditions and develop consensus‐based guidance for clinicians. Results This statement outlines the outcomes of the Summit, including considerations for prescribers, primary care professionals, emergency personnel, and health care system stakeholders. These considerations are intended to improve identification of patients as appropriate candidates for AAT, management of patients with co‐occurring AD and cardiovascular conditions, and their emergency evaluation and treatment. The statement also includes guidance for shared decision‐making, implementation of system changes for improving dementia care, and recommendations for future research and data collection to add to the body of evidence for treating patients with concomitant AD and cardiovascular conditions. Conclusions Building on lessons learned from the establishment of stroke systems of care, the consensus‐based considerations outlined in this document can serve as a foundation for AD systems of care aimed at ensuring optimal use of these ground‐breaking therapies.

Abstract Objective Surgery is an effective, yet underutilized treatment for children with drug‐resistant epilepsy. Although predictors of surgical outcomes are well described, the decision to recommend surgery varies by institution. We aim to evaluate the rates of not recommending surgery, identify associated patient characteristics, and quantify variability across centers. Methods We queried the Pediatric Epilepsy Research Consortium Surgery database, a prospective multicenter cohort of children (0–18 years) undergoing initial evaluation for epilepsy surgery. Patients with documented surgical decisions were included. Demographic, clinical, and presurgical evaluation variables were compared by surgical recommendation status. Logistic regression identified factors associated with not recommending surgery. Mixed‐effects models quantified between‐center variability. Results Among 2480 patients across 29 centers, 532 (21%) were not recommended epilepsy surgery (median center rate 17%, interquartile range [IQR] 10%–28%). After accounting for patient characteristics associated with surgical candidacy, substantial variation in decision‐making remained across centers, with a median twofold difference in the odds of not recommending surgery between otherwise similar patients evaluated at different institutions (Median Odds Ratio = 2.25; Intraclass Correlation Coefficient = .18). The clinical characteristics most strongly associated with not recommending surgery included monthly or less frequent seizures (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.75–2.69), non‐structural etiology (OR 2.02, 95% CI 1.56–2.61), and taking ≤2 anti‐seizure medications (ASMs) (OR 1.67, 95% CI 1.34–2.08, all p 's < .01). These characteristics showed minimal clustering across centers (ICCs < .05). Significance One in five children evaluated for epilepsy surgery are not recommended to pursue surgical treatment. Although clinical factors influence decision‐making, they do not explain the substantial variation in recommendations across pediatric epilepsy centers. Similar children evaluated at different institutions had significant differences in the odds of not being recommended surgery, suggesting that institutional decision‐making contributes importantly to surgical candidacy.

Abstract Purpose Validate the semiquantitative (SQ)-MRI score for chronic pancreatitis (CP) diagnosis in an independent, multicenter cohort. Methods We analyzed MRIs performed at baseline in 337 participants with acute (AP) or recurrent AP (RAP) and 67 with non-calcific chronic pancreatitis (NCCP) enrolled in the PROCEED study from 6/2017 to 3/2023. MRIs were performed at multiple clinical centers using site-specific clinical protocols and a variety of MRI vendors to evaluate the SQ-MRI score in a real-world setting. The SQ-MRI score was calculated using the T1 signal intensity ratio of the pancreas to the spleen (T1 score), arteriovenous enhancement ratio (AVR), and pancreatic body diameter (PBD). We adjusted for confounding by participant characteristics via propensity score weighting. Results Median AVR was higher in AP/RAP (1.18, IQR: 0.97–1.44) than in the NCCP group (1.03, IQR: 0.78–1.22, p = 0.007). Pancreatic body diameters were larger in AP/RAP than in the NCCP group − 7–14 mm (10% vs 25%), 14–20 mm (40% vs 54%), and > 20 mm (50% vs 21%), respectively ( p < 0.01). Median T1 score was higher in AP/RAP (1.18, IQR: 0.96–1.40) than in the NCCP group (1.04, IQR: 0.86–1.32, p = 0.10). Median SQ-MRI score in the AP/RAP group was significantly lower, 1.91 (IQR: 0.97, 2.95), than in the NCCP group, 2.74 (IQR: 2.04–4.03) ( p < 0.001). The propensity score-adjusted AUC for SQ-MRI to distinguish AP/RAP from NCCP was 0.64, which was higher than for individual parameters. Conclusion We have validated the SQ-MRI score in a multicenter cohort using an independent, real-world MRI dataset.

ABSTRACT Herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV) are associated with a range of clinical manifestations depending on the anatomical site of infection. HSV and VZV lesions often exhibit similar phenotypical characteristics, making clinical differentiation challenging. Detection and differentiation of HSV-1, HSV-2, and VZV are essential for diagnosis and treatment management. An automated multiplex real-time PCR assay, Alinity m HSV 1 & 2/VZV assay, was developed to detect and differentiate HSV-1, HSV-2, and VZV. The assay was validated for use with cutaneous and mucocutaneous lesion swab specimens collected in commercial viral transport media from symptomatic patients. The assay demonstrated a limit of detection of 5.90 TCID 50 /mL for HSV-1, 2.07 TCID 50 /mL for HSV-2, and 0.055 TCID 50 /mL for VZV. Testing with clinical swab specimens demonstrated greater than 95% clinical sensitivity and specificity for all three analytes. The Alinity m HSV 1 & 2/VZV assay provides a reliable and accurate method for detection and differentiation of HSV-1, HSV-2, and VZV in lesion swab specimens for improved diagnostic accuracy and patient management. IMPORTANCE Herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV) can cause skin and mucocutaneous lesions that often appear clinically similar, making accurate diagnosis difficult without laboratory testing. Rapid and reliable identification of the causative virus is important because patient counseling, treatment decisions, and infection management differ among these infections. In this multicenter study, a fully automated molecular assay was evaluated that simultaneously detects and differentiates HSV-1, HSV-2, and VZV from a single-lesion swab specimen. Testing of more than 1,200 clinical specimens demonstrated high sensitivity and specificity for all three viruses. The assay also offers a streamlined workflow with minimal hands-on time and rapid turnaround. These findings support the use of this multiplex assay as a practical diagnostic tool that can improve laboratory efficiency and provide clinicians with timely, accurate results to guide patient care.

ABSTRACT Background Post‐pancreatectomy exocrine insufficiency is common after resection for pancreatic cancer and requires pancreatic enzyme replacement therapy (PERT). We sought to determine the out‐of‐pocket cost of PERT and the association between PERT and survival. Methods The SEER‐linked Medicare database was queried for patients with pancreatic cancer who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) from 2010 to 2019. Cumulative out‐of‐pocket costs were calculated and stratified by procedure and radiation. Results 11,854 Medicare beneficiaries with resected pancreatic cancer were identified, 4,653 (39%) required PERT and 7,201 (61%) did not. Median age was 73.0, 50.6% were female and 83.6% White. 25.9% underwent DP and 74.1% underwent PD; 7% received neoadjuvant radiation while 23.5% received adjuvant radiation. Logistic regression demonstrated that female sex (OR 1.25, 95% CI 1.16‐1.35, p < 0.001), neoadjuvant radiation (OR 1.93, 95% CI 1.67‐2.24, p < 0.001), and PD (OR 2.45, 95% CI 2.23‐2.7, p < 0.001) were risk factors for requiring PERT. Patients without subsidies who underwent DP paid a cumulative $4,736 out‐of‐pocket for PERT after 5 years, those who underwent PD paid $5,601 out‐of‐pocket. Conclusions Nearly 40% of Medicare beneficiaries took PERT after resection for pancreatic cancer and paid thousands in out‐of‐pocket costs. While a conservative estimate, these findings highlight the importance of addressing this financial burden to patients.