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BACKGROUND: Pulsed field ablation is now widely used for atrial fibrillation (AF) ablation, but atrial tachyarrhythmia recurrence remains common and postablation risk tools are limited. We assessed whether a validated sinus‑rhythm artificial intelligence— enabled ECG AF probability score, and its early postablation change, predicts recurrence after pulsed field ablation. METHODS: We studied consecutive patients undergoing index pulsed field ablation across 3 Mayo Clinic sites (February 2024–March 2025) with ≥1 sinus‑rhythm ECG within 180 days preprocedure. Baseline artificial intelligence—enabled ECG AF score (range 0–1) was the mean across baseline ECGs. Recovery indices (RI30/60/90), defined as mean postprocedure artificial intelligence—enabled ECG score within days 1–30/60/90 minus baseline, predicted post‑blanking recurrence using corresponding 30‑, 60‑, and 90‑day blanking windows. The primary outcome was time to first documented AF/atrial flutter/atrial tachycardia episode >30 seconds, ascertained via clinic ECGs, ambulatory monitoring, and device interrogations. Cox regression adjusted for prespecified clinical and echocardiographic covariates assessed associations; Harrell C‑statistic quantified discrimination. RESULTS: Among 1052 patients (67±10 years; 33% women), median baseline score was 0.35; 320 (30%) recurred over 188 days. Higher baseline score independently predicted recurrence (hazard ratio per 0.1 increase, 1.08 [95% CI, 1.03–1.14]). Scores rose on day 0 after ablation, then declined over subsequent weeks, with persistently higher, less‑improving trajectories among patients who recurred (time×recurrence interaction P <0.001). Day 0 score was not independently associated with recurrence after adjustment. Attenuated early recovery (higher recovery index) was independently associated with recurrence, most robustly for RI-90 (hazard ratio per 0.1 increase, 1.15 [95% CI, 1.07–1.24]), and improved discrimination beyond baseline and covariates (C‑statistic, 0.63–0.67; ΔC=0.04). Findings were consistent in a historical thermal ablation cohort. CONCLUSIONS: Baseline and early postablation dynamics of a sinus‑rhythm artificial intelligence—enabled ECG AF probability score are associated with pulsed field ablation recurrence and may aid multivariable risk stratification; prospective validation is warranted.

Importance Rapid whole-genome sequencing (WGS) has advanced inpatient genetic diagnosis, although most evidence comes from neonatal and pediatric intensive care unit (ICU) populations. Its utility for pediatric neurology inpatients across broader acute settings remains insufficiently established. Objective To assess the diagnostic yield, clinical impact, and factors associated with phenotype-concordant rapid WGS diagnoses. Design, Setting, and Participants This was a retrospective cohort study conducted from June 1, 2022, through January 17, 2026, at a tertiary medical center. Pediatric inpatients in the neonatal ICU, pediatric ICU, or general floor with an unexplained neurologic presentation were included. Those with established nongenetic etiology were excluded from analyses. Exposures Trio (77.8%), duo (9.1%), or singleton (13.1%) rapid WGS. Main Outcomes and Measures The primary outcome was the initial phenotype-concordant diagnostic yield at the point of care. Secondary outcomes were reanalysis yield (new diagnoses from reinterpreting nondiagnostic cases prompted by a new unexplained phenotype or family request), cumulative yield, and management change. Associations were assessed by logistic regression (odds ratios [ORs] and 95% CIs). Results Among 175 children (median [IQR] age, 4 months [1 day-4 years]; 93 male [53.1%]) who met inclusion criteria (82 neonates, 93 nonneonates), initial rapid WGS established a phenotype-concordant diagnosis in 79 (45.1%), higher in nonneonates (49 of 93 [52.7%]) than neonates (30 of 82 [36.6%]). Preliminary results returned at mean (SD) 4.0 (1.6) days and final reports at 10.4 (4.5) days. Positive nonconcordant findings occurred in 33 children (18.9%). Reanalysis of 14 nondiagnostic cases yielded 3 additional diagnoses, for a cumulative yield of 82 of 175 children (46.9%). Most diagnoses were monogenic (63 [76.8%]). Management changed in 54 of 82 phenotype-concordant cases (65.9%; 53 at the point of care, 1 after reanalysis) and 8 of 33 (24.2%) positive nonconcordant cases. Family history was most strongly associated with diagnosis (adjusted OR [aOR], 6.46; 95% CI, 3.23-12.93; P &amp;lt; .001), followed by multisystem involvement (aOR, 2.85; 95% CI, 1.24-6.54; P = .01) and congenital anomaly or dysmorphism (aOR, 2.47; 95% CI, 1.07-5.68; P = .03). Hypotonia was most strongly associated in neonates (OR, 20.63; 95% CI, 5.46-77.87; P &amp;lt; .001); ICU admission (OR, 10.25; 95% CI, 2.79-37.67; P &amp;lt; .001) predominated in nonneonates. Conclusions and Relevance Results of this cohort study suggest that rapid WGS diagnosed nearly half of pediatric neurology inpatients and changed management in two-thirds of diagnosed cases, supporting its potential use as early diagnostic testing. Associated features may guide patient selection, and reanalysis extends yield longitudinally.

Background The Impella 5.5 is employed to provide left ventricular support in cardiogenic shock. Mechanistic understanding of biventricular relationships is essential in device optimization. Using a porcine model of acute myocardial infarction in tandem with pressure–volume loops, this study aimed to understand the impact of Impella 5.5 on biventricular hemodynamics. Methods Using Domestic Yorkshire pigs, an Impella 5.5 was inserted percutaneously under fluoroscopic guidance via carotid/aortic access and an acute myocardial infarction was created. Biventricular pressure–volume loops and derived parameters were generated for each level of support before (n=6) and after myocardial infarction (n=6). Results With increasing Impella 5.5 support, left ventricular pressure–volume loops shifted left, and right ventricular (RV) loops shifted right. In a healthy porcine heart, the RV adequately compensated for increased preload from the device, demonstrated by increased RV performance at higher P levels. After myocardial infarction, pigs were unable to tolerate speeds beyond P7 from diminished RV stroke volume reserve compared to healthy hearts. Median RV stroke volume percentage change from P1 to P9 before myocardial infarction was from 5.7% (interquartile range, −15.1% to 9.7%) to 50.6% (interquartile range, −11.6% to 60.2; P <0.05), and following acute myocardial infarction from P1 to P7 was from 3.9% (interquartile range, −2.7 to 78.4) to 13.4% (interquartile range, −8.9% to 147.2; P =0.94). Conclusions Impella 5.5 speed modulation highlights significant interventricular interactions with opposing biventricular trends. While the heart can mount an improvement in RV stroke volume with increasing Impella 5.5 support, these data suggest an attenuated response following acute myocardial infarction, which may relate to inadequate response to increased preload needed by the device after infarction affecting the interventricular septum.

Abstract Introduction Quantitative interpretation of pediatric brain [ 18 F]-FDG PET is limited by the lack of age-matched normative reference databases, despite substantial developmental variation in cerebral glucose metabolism. This study aimed to construct a large-scale normative pediatric [ 18 F]-FDG PET database and develop an age-specific z-score mapping framework for quantitative evaluation of pediatric epilepsy. Method Pediatric brain PET data were retrospectively derived from clinically acquired whole-body or dedicated [ 18 F]-FDG PET examinations in participants 0–19 years of age without neurologic disease or visible brain abnormalities. A total of 417 PET scans from 341 participants were stratified into five developmental age groups: infancy, early childhood, middle childhood/school age, adolescence, and late adolescence. SUVR maps were generated using whole-brain atlas and brainstem reference regions. Voxel-wise t-test analyses were performed to characterize age- and sex-related metabolic differences. Age-specific voxel-wise mean and standard deviation maps were generated from the normative cohort and used to calculate age-matched hypometabolic z-score maps in 14 pediatric patients with epilepsy. The resulting abnormalities were qualitatively evaluated for concordance with epileptogenic findings identified on clinical MRI and/or PET by expert image review. Results Voxel-wise analyses demonstrated prominent age-dependent SUVR differences, particularly between infancy and older age groups. With whole-brain atlas normalization, older children showed progressively higher relative SUVR in cortical and cerebellar gray matter regions, whereas infancy showed relatively higher SUVR in the occipital cortex, white matter, thalamus, and brainstem. Brainstem normalization produced distinct developmental patterns, emphasizing higher white matter SUVR in infancy and broader gray matter differences in older groups. Sex-related differences were limited and regionally specific. Whole-brain atlas normalization showed lower variability than brainstem normalization and was selected for z-score mapping. In representative epilepsy cases, age-matched z-score maps identified focal or regional hypometabolism corresponding to malformations of cortical development, focal cortical dysplasia, mesial temporal sclerosis, nonlesional MRI cases, remote insult, tumor-related abnormalities, and Sturge-Weber syndrome. Discussion A large-scale normative pediatric [18F]-FDG PET database can support developmentally appropriate quantitative interpretation of pediatric brain PET. Age-matched z-score mapping may complement visual assessment by highlighting abnormal cerebral glucose metabolism in pediatric epilepsy, although findings should be interpreted with MRI, EEG, seizure semiology, and other presurgical data.

Abstract The paradigm in the field of oncolytic virotherapy proposes that tumor cell killing by an oncolytic virus (OV) culminates in the priming of antitumor CD8+ T cells. However, this ignores the impact a highly immunodominant antiviral response against the OV has on the subdominant antitumor response, particularly with regard to the naturally low affinity of tumor antigens to their cognate T-cell receptors. To investigate this experimentally, we first studied the interaction between the two responses in B16 and MC38 tumor models, both expressing ovalbumin (OVA). Contrary to the accepted paradigm, the inflammatory vesicular stomatitis virus (VSV) failed to expand OVA-specific T cells in vivo unless armed with tumor-associated antigen (TAA). In fact, treatment with the control VSV led to the ablation of antitumor T cells and a shift toward dysfunction as determined by the upregulation of markers, including LAG3 and CD39, correlating with lower rates of survival. Combination with anti–PD-1 immune checkpoint blockade therapy significantly improved survival only when VSV expressed TAA. VSV-expressing altered peptide ligand variants of tumor antigens, which evade mechanisms of central tolerance, expanded near self-antigen–specific T cells with the ability to cross-react with tolerized tumor antigens, thus providing an antitumor effector population capable of proliferating in the presence of a potent antiviral response. Taken together, these findings offer a rational approach to OV design which preserves acute antitumor therapy provided by antiviral innate and T-cell responses while promoting the induction of tumor-specific T cells. Significance: Oncolytic viruses can induce an antiviral T-cell response that occludes an antitumor response, challenging the paradigm in the field and elucidating strategies to optimize the efficacy of oncolytic viroimmunotherapy.

Background Bicuspid aortic valve (BAV) is the most common congenital heart defect, associated with a lifetime morbidity burden exceeding 80% and an estimated 7% probability of transmission to first-degree relatives. Hence, echocardiographic screening of relatives is recommended. The aim of our study is to develop an artificial intelligence-enabled electrocardiogram (AI-ECG) model for the detection of BAV. Methods Between January 1, 1990, and June 30, 2023, the Mayo Clinic healthcare system database was searched for patients aged ≥18 years with echocardiograms performed for family history of BAV, abnormal auscultation, a BAV-related diagnosis, or to rule out the condition, and with an electrocardiogram (ECG) obtained within 6 months. Cases were patients with a confirmed BAV diagnosis, and controls were those with normal aortic valves. ECGs were randomly assigned into training (80%), internal validation (10%), and test (10%) groups. The AI-ECG model was built using Keras under TensorFlow. Results A total of 13,065 valid ECG–echocardiogram pairs were included (mean [SD] age, 58 [17] years; 44% women), with a median time of 1 day (interquartile range, 0–3 days) between studies. With a 45% BAV prevalence in the test group ( n = 1301), the area under the curve was 0.704, positive predictive value (PPV) 60.1%, and negative predictive value (NPV) 69.4%. At a prevalence of 7%, the NPV increased to 96.1%, but the PPV decreased to 12.2%. Conclusions In this retrospective cohort and using the current AI-ECG model, BAV detection showed modest diagnostic performance and limited standalone clinical utility, suggesting that ECG-only screening for BAV may require additional modalities or more refined phenotyping.

Background Menopause-related symptoms are common but undertreated. Digital tools that support symptom assessment and patient education may improve engagement. Objective To assess whether a previsit digital menopause symptom assessment and education tool increased treatment initiation and patient engagement compared to an educational pamphlet. Design Women aged 45–55 years with upcoming primary care appointments were invited to participate. Those with a total Menopause Rating Scale (MRS) score ≥5 indicating bothersome menopause symptoms were included. Participants were randomized to a digital menopause symptom assessment tool or a digital educational pamphlet and completed a post-visit survey (NCT06919887). Participants Of the 14,726 women invited to participate between May 12, 2025, and December 5, 2025, there were 653 (4.4%) enrolled that met eligibility criteria. Interventions Randomized to an mHealth app called emmii or a standard digital menopause educational pamphlet. Main measures Menopause treatment initiation within 30 days of the clinical visit was assessed by electronic health data. Baseline and post-visit surveys were collected assessing patient experience, engagement, and perceived usefulness. Rates of menopause hormone therapy (HT) prescribing were compared with a reference population of nonparticipants aged 45–55 who had a primary care appointment at Mayo Clinic during the same period and received no study education materials. Key results Of 653 participants enrolled and randomized, 383 completed both the baseline and post-surveys (171 intervention and 212 control). HT initiation among study participants was significantly higher than in the reference population of women (9.3% vs. 4.4%, p &lt; 0.001). There was no difference in HT initiation between the intervention (9.1%) and control groups (9.6%) ( p = 0.83). Initiation rates were 3.8% and 4.5%, respectively ( p = 0.64) for nonhormone therapies. Conclusions Among women with bothersome menopause symptoms, those who underwent previsit symptom screening and received educational materials had higher rates of HT initiation than women who did not participate in the study. These findings suggest that structured menopause education may improve recognition and management of menopause symptoms in routine clinical practice.