Citations

Background Disruption in rest‐activity rhythm (RAR) is an emerging risk factor for cardiovascular disease (CVD) and mortality, but the strength of evidence is unclear. Therefore, we conducted a systematic review and meta‐analysis to assess associations between RAR characteristics and cardiovascular disease incidence or prevalence, cardiovascular mortality, and all‐cause mortality. Methods A systematic search was conducted in PubMed, Web of Science, Cochrane Library, and Embase for cohort or cross‐sectional studies published up to August 2025. The exposure variables were nonparametric RAR parameters, including interdaily stability (describing day‐to‐day stability of the RAR), intradaily variability (a measure of RAR fragmentation), and relative amplitude (indicating robustness or strength of the RAR). The primary outcomes were cardiovascular mortality and all‐cause mortality. The secondary outcomes included cardiovascular disease prevalence and incidence. Results Seven studies involving 109 365 participants were included. Pooled results showed that higher intradaily variability was associated with a significantly increased risk of all‐cause mortality (hazard ratio [HR], 1.05 [95% CI, 1.02–1.09]) and cardiovascular disease prevalence (odds ratio, 1.73 [95% CI, 1.21–2.47]). Lower relative amplitude was significantly associated with higher cardiovascular mortality (HR, 1.50 [95% CI, 1.13–1.98]) and all‐cause mortality (HR, 1.46 [95% CI, 1.27–1.68]). Interdaily stability showed no significant associations with any outcome. Conclusions Measures of disrupted rest‐activity rhythms were associated with increased cardiovascular mortality, and all‐cause mortality. These findings support using RAR metrics as early, noninvasive risk indicators. Future work should investigate whether appropriately timed physical activity and sleep, as well as other interventions targeting RAR can mitigate cardiovascular risk.

Background/Objectives: Glioblastoma surveillance after surgery and chemoradiation remains challenging because MRI findings of tumor recurrence can overlap with pseudo-progression, treatment-related effects, and postoperative tissue changes. Methods: We developed a seven-channel postoperative MRI framework using a deep learning transfer method to support non-invasive glioblastoma treatment-effect assessment. The model used T1 contrast-enhanced, FLAIR, T1, RSI-Cell, ADC, T2, and cerebral blood flow volumes from 124 postoperative glioblastoma patients (164 MRI timepoints) as input. Images were processed using a 3D ResNet18 encoder pretrained on 588 postoperative glioma samples and fine-tuned using task-specific classification heads. The cohort comprised 124 patients contributing 164 postoperative MRI timepoints, all acquired at 3T on scanners from a single vendor. Performance was evaluated with nested five-fold cross-validation stratified and assigned at the patient level, so that all timepoints from a given patient fell in one-fold and the training epoch was selected on an inner split rather than on the fold being reported. Because some of the clinical labels were incomplete, the number of evaluable timepoints differed by task (recurrence versus pseudo-progression, 164; MGMT, 99; short-term survival, 139). The whole procedure was repeated under three independent random seeds and results are reported as the mean and standard deviation across seeds. Results: The strongest clinical endpoint was recurrence versus pseudo-progression, where nested cross-validation across three random seeds gave a pooled out-of-fold AUC of 0.935 (SD = 0.014), area under the precision-recall curve of 0.973, balanced accuracy of 0.880, sensitivity of 0.917, and specificity of 0.843. No other endpoint reached reliable discrimination. Radiation decision reached an AUC of 0.658 (SD = 0.039), while MGMT promoter methylation (AUC = 0.532, SD = 0.082) and short-term survival (AUC = 0.514, SD = 0.027) were indistinguishable from chance. Conclusions: In this single-center proof-of-concept study, postoperative MRI successfully distinguished tumor recurrence from pseudo-progression. However, the models did not reliably predict the other three outcomes related to molecular status, treatment planning, and prognosis. Overall, the model learned imaging features specifically associated with recurrence, rather than a more general representation of the tumor that can predict many different clinical outcomes. These findings support technical feasibility for a single endpoint rather than clinical readiness, for which external multi-center validation is required.

BACKGROUND: It is unknown whether cardiac resynchronization therapy (CRT) improves systemic metabolomic profile by enhancing left ventricular function. The observational cohort study aimed to investigate the effect of CRT on left ventricular ejection fraction (LVEF) and circulating plasma metabolites in patients who had heart failure with reduced LVEF. METHODS: We prospectively screened patients with ischemic cardiomyopathy and nonischemic cardiomyopathy who received CRT with a defibrillator for LVEF ≤35% according to current guidelines. Clinical assessment included echocardiography and device interrogation. Blood samples for metabolomic analysis were collected before CRT and at 6-month follow-up. Plasma was subjected to gas chromatography-mass spectrometry and 1 H nuclear magnetic resonance-based metabolomic analysis. RESULTS: Totally 92 patients were enrolled, with a mean age of 67.3±11.3 years (37.0% female). LVEF was significantly improved from 28.9±7.6% at baseline to 36.0±11.3% at 6 months ( P <0.001) and to 40.1±12.6% at 12 months ( P <0.001). After CRT, 42 metabolite features were significantly decreased compared with the baseline. The ketone bodies, including 3-hydroxybutyrate ( P <0.001) and acetone ( P =0.01), were reduced. A branched-chain amino acid, isoleucine, was also decreased after CRT ( P =0.01). These metabolomic changes were mainly observed in the nonischemic cardiomyopathy group, while the metabolomic profile in the ischemic cardiomyopathy group was characterized by enhanced amino acid oxidation and elevated levels of lactate and pyruvate. The improvement in LVEF positively correlated with the ratio of changes in ketone bodies and isoleucine. CONCLUSIONS: CRT may modulate the systemic plasma metabolomic profile, which correlated with improvement in left ventricular function in patients with severe heart failure with reduced ejection fraction.

Abstract Background Recurrence of symptomatic atrial fibrillation (AF) after catheter ablation (CA) is not uncommon. However, real-world long-term data on clinical outcomes of rhythm control strategies in patients with recurrent AF after CA remain limited. Methods Using the TriNetX database, we identified adult patients (≥18 years) with recurrent AF after index CA. A 3-month blanking period was applied, during which no rhythm-control therapy was received. Patients were classified into two groups: repeat CA or initiation of antiarrhythmic drug (AAD) therapy. Propensity score matching (PSM) was performed to balance baseline characteristics. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Outcomes included all-cause mortality, all-cause hospitalization, heart failure (HF) exacerbation, ischemic stroke, and major bleeding over 5 years. Results Among 4,056 patients with recurrent AF post-CA, 17.2% underwent repeat CA. After PSM, 697 patients in the repeat CA group (mean age 68.9 ± 9.6 years; 35.7% female) and 697 in the AAD group (mean age 68.4 ± 10.0 years; 37.6% female) were analyzed. Repeat CA was associated with lower all-cause mortality (3.3% vs 8.2%; HR 0.44; 95% CI, 0.27–0.72; P &lt; 0.01), all-cause hospitalization (42.8% vs 56.4%; HR 0.71; 95% CI, 0.61–0.82; P &lt; 0.01) and HF exacerbation (12.5% vs 24.8%; HR 0.50; 95% CI, 0.39–0.64; P &lt; 0.01). No differences were observed in ischemic stroke (5.3% vs 4.7%; HR 1.22; 95% CI, 0.77–1.96; P = 0.40) or major bleeding (4.6% vs 6.2%; HR 0.82; 95% CI, 0.52–1.29; P = 0.39). Conclusions Repeat CA was associated with lower mortality, hospitalization, and HF exacerbation over 5 years.

Abstract Background Vagally mediated syncope and functional bradyarrhythmias can cause recurrent symptoms, injury and a need for permanent pacing, yet standard therapies do not address the underlying autonomic reflex. Cardioneuroablation (CNA) targets this mechanism, but adoption has been limited by uncertainty about patient selection, procedural endpoints and durable outcomes. Methods We studied 95 consecutive patients with vagally mediated syncope (n=78) or functional bradyarrhythmia (n=17) who underwent CNA at a single center by a single lead operator under a uniform, prospectively maintained protocol. Extracardiac vagal stimulation (ECVS) was performed before and after ablation to confirm vagally mediated sinus or atrioventricular (AV) nodal responses and to verify their attenuation. Outcomes through 1 year included clinical recurrence, quality of life, pacing burden and pacemaker extraction. Results Before ablation, ECVS provoked sinus pauses in 95.8% of patients and AV block in 91.6%; after ablation, sinus pauses were abolished in every patient and residual AV block was present in 4.2%. One-year freedom from recurrent syncope and from bradyarrhythmia-related events was 93.8% and 94.1%. Syncope burden fell from a median of 2.7 episodes per year to none, and disease-specific quality of life improved substantially (P<0.001). Among patients with pre-existing devices, atrial pacing burden fell from a median of 22% to 0%. There were no strokes, deaths or myocardial infarctions. Conclusions In this single-center cohort, physiology-guided CNA was associated with durable symptom control, improved quality of life and reduced pacing across vagally mediated bradyarrhythmia syndromes. Multicenter controlled studies are needed to confirm these findings.

Accurate estimation of Alzheimer’s disease (AD) severity from structural magnetic resonance imaging (MRI) remains difficult, as disease-associated anatomical alterations are often subtle and publicly available datasets are typically too small to support robust deep learning model training. This feasibility study sought to determine how much Alzheimer’s disease spectrum-related information could be extracted from a small structural MRI cohort using a deliberately lightweight two-dimensional convolutional neural network (2D CNN), and whether transfer learning improves model performance. This study was intended as a methodological proof of concept rather than the development of a clinically deployable diagnostic tool. Structural scans and Clinical Dementia Rating (CDR) labels from the OASIS-1 dataset were filtered to 214 subjects: 124 cognitively normal (CN), 65 with mild cognitive impairment (MCI; CDR = 0.5), and 25 with AD-level impairment (CDR ≥ 1). A compact 2D CNN trained from scratch and a transfer learning model (frozen ImageNet MobileNetV2 features) were evaluated on four binary tasks (CN vs. AD, MCI vs. AD, CN vs. MCI, and CN vs. any impairment) under identical pre-processing and subject-level repeated 5-fold cross-validation (10 repeats), with the decision threshold tuned only on an inner split. Discrimination was summarized by ROC-AUC with 95% confidence intervals (CIs), permutation tests against chance, and per-task sensitivity and specificity. The from-scratch CNN recovered only a broad normal-versus-impaired signal (CN vs. any impairment AUC 0.59) and was at chance on adjacent-stage tasks (MCI vs. AD 0.41; CN vs. MCI 0.51). Transfer learning improved every task: CN vs. AD AUC 0.745 (95% CI 0.730–0.763), CN vs. any impairment 0.642, CN vs. MCI 0.601, and MCI vs. AD 0.599. On an independent OASIS-2 cohort, the transfer learning CN vs. AD model retained AUC 0.748. In this small-data regime, transfer learning recovers substantially more Alzheimer-spectrum signals than a from-scratch CNN, but performance remains modest because it is bounded by CDR-based, non-biomarker-confirmed labels, suggesting the model separates CDR-defined cognitive-status groups rather than detecting AD pathology.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Abstract Background Opportunistic bilateral salpingectomy (OBS), the removal of fallopian tubes during hysterectomy or instead of tubal ligation, is recommended to reduce ovarian cancer risk. However, data on the effectiveness of prophylactic OBS is limited. Methods This population-based retrospective cohort included individuals aged 18–80 in Ontario, Canada, who underwent OBS or comparator surgeries (hysterectomy with ovarian and tubal conservation or tubal ligation) from 2011 to 2023. Individuals with gynecologic cancer before or within six months of surgery were excluded. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Sensitivity analyses varied the time between surgery and cancer diagnosis to account for pre-existing serous tubal intraepithelial carcinomas. Results Among 196,839 individuals, 57,941 underwent OBS and 138,898 underwent comparator surgeries. 142 epithelial ovarian cancers were diagnosed (19 in the OBS group and 123 in the comparator surgery group). OBS was associated with reduced risk of any ovarian carcinoma, with an adjusted hazard ratio (aHR) of 0.60 (95% CI, 0.36 to 0.98). For serous ovarian carcinoma (high- and low-grade combined due to missing grade data), the aHR was 0.47 (95% CI, 0.22 to 0.99). Sensitivity analyses with 12- and 18-month intervals showed aHRs of 0.59 (95% CI, 0.35 to 0.99) and 0.60 (95% CI, 0.35 to 1.01) for all ovarian carcinomas, and 0.49 (95% CI, 0.23 to 1.01) and 0.47 (95% CI, 0.22 to 0.99) for serous ovarian carcinoma, respectively. Conclusions OBS was associated with reduced risk of ovarian carcinoma, supporting its role as a primary prevention strategy.

Abstract Background Cardiac magnetic resonance elastography (MRE) allows the non-invasive quantification of myocardial stiffness, but long-interval reproducibility data at 3.0 T single-frequency 140-Hz remain limited. Purpose To evaluate the short- and long-interval reproducibility of 3.0 T cardiac MRE for left ventricular (LV) myocardial stiffness across healthy volunteers and patients with conditions associated with elevated myocardial stiffness. Materials and Methods This prospective single-center study included 69 participants: 60 healthy volunteers and 9 with cardiovascular disease (6 with aortic stenosis and 3 with long-standing hypertension). All participants underwent baseline cardiac MRE (scanner: Signa Premier 3.0 T, GE Healthcare, driver: Resoundant), an immediate short-interval rescan (SIR) within 5 minutes, and a long-interval rescan (LIR) after approximately 1 month. Left ventricular myocardial stiffness and octahedral shear strain signal-to-noise ratio were measured independently by 2 readers. Reproducibility was assessed using Bland-Altman analysis, intraclass correlation coefficients (ICCs), within-subject coefficient of variation, standard error of measurement, and smallest detectable change at the 95% confidence (SDC95) level. Results Baseline LV myocardial stiffness was higher in the disease group than in healthy volunteers, 11.73 ± 1.01 kPa and 7.80 ± 0.70 kPa (mean ± SD; P &lt; .001), respectively. Inter-reader agreement was excellent across all timepoints, with ICCs of 0.970 at baseline (95% CI, 0.953-0.982), 0.966 for SIR (95% CI, 0.945-0.979), and 0.962 for LIR (95% CI, 0.939-0.976). Within-reader scan-rescan reproducibility was also excellent. For Reader 1, stiffness ICC was 0.979 for the SIR (95% CI, 0.966-0.987) and 0.957 for the LIR (95% CI, 0.932-0.973), with SDC95 values of 0.616 kPa (95% CI, 0.528-0.741) and 0.869 kPa (95% CI, 0.744-1.044), respectively. Reader 2 showed excellent reproducibility, with ICCs ≤0.943. Conclusions 3D single-frequency 140-Hz cardiac MRE at 3.0 T provides excellent short- and long-interval reproducibility for LV myocardial stiffness quantification. The SDC95 values may help distinguish true longitudinal stiffness changes from measurement variability.