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Importance Primary brain and central nervous system cancer (collectively referred to as CNS cancer) comprises 2% of all human cancers and poses significant health and economic challenges in the United States. Objective To analyze CNS cancer burden in the US, stratified by time, location (state and division), sex, age group, and Sociodemographic Index (SDI). Design, Setting, and Participants This cross-sectional study involved a repeated analysis of Global Burden of Disease Study (GBD) 2021 data in 2024. Using data from 183 sources, CNS cancer metrics in the US were estimated across states and years. US CNS cancer metrics across all sexes and age groups were included in the GBD. Exposure CNS cancer diagnosis. Main Outcomes and Measures Overall and age-standardized estimates of the incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability per 100 000 population, including 95% uncertainty intervals (UIs), and time trends. Results In 2021, for all age groups and sexes across the US, there were 31 780 incident cases (95% UI, 29971.1 to 32843.9). Age-standardized incidence, DALYs, and mortality rates per 100 000 population were 6.91 (95% UI, 6.58 to 7.12), 134.38 (95% UI, 129.83 to 137.95), and 4.1 (95% UI, 3.87 to 4.22), respectively. Despite no significant change observed in the overall incidence between 1990 and 2021, DALY and mortality rates decreased by 15.77% (95% UI, −17.75% to −13.68%) and 8.41% (95% UI, −11.09% to −6.22%), respectively. Substantial geographic variability was noted. Mississippi, Alabama, Kentucky, and Kansas (West North Central and East South Central divisions) and West Virginia faced persistently high burdens over the past 30 years. Sex differences were evident; disease burden was consistently higher in males compared with females. Age-specific estimates showed a bimodal distribution: the youngest group (<5 years) showed a significant decrease in incidence rate (−34.42% to −11.56%), whereas older age groups (>70 years) experienced increasing trends. DALYs and mortality rates were negatively correlated with SDI (ρ = −0.6860 and ρ = −0.6391; P < .001). Conclusions and Relevance These findings provide valuable insights into the CNS cancer burden across the US by age, sex, location, and SDI, enabling better public health status assessments, health care policy restructuring, and resource redistribution for improved care.

Background: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case–control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression models and the area under the receiver operating characteristic curve (AUC) were estimated. Results: PRS for invasive disease showed a stronger association in younger (<50 years) women (OR = 2.51, AUC = 0.622) than in women ≥ 50 years (OR = 2.06, AUC = 0.653) of European ancestry. PRS performance in Asians was lower (OR range = 1.62–1.64, AUC = 0.551–0.600). Gail performance was modest across groups and poor in younger Asian women (OR = 0.94–0.99, AUC = 0.523–0.533). Age interactions were observed for both PRS (p < 0.001) and Gail (p < 0.001) in Europeans, whereas in Asians, age interaction was observed only for Gail (invasive: p < 0.001; DCIS: p = 0.002). PRS identified more high-risk individuals than Gail in Asian populations, especially ≥50 years, while Gail identified more in Europeans. Overlap between PRS, Gail, and family history was limited at higher thresholds. Calibration analysis, comparing empirical and model-based ROC curves, showed divergence for both PRS and Gail (p < 0.001), which indicates miscalibration. In Europeans, family history and prior biopsies drove Gail discrimination. In younger Asians, age at first live birth was influential. Conclusions: PRS adds value to risk stratification beyond traditional tools, especially in younger women and Asian ancestry populations.

Introduction: Artificial intelligence (AI) and wider digital technologies are accelerating healthcare systems’ attempts to address the financial and moral imperatives of improving health disparities and thus wider population health outcomes. Yet adoption has thus far been slower in less common conditions including carcinoid, its syndrome, and related heart disease especially amid wider system shocks like the COVID-19 pandemic and its lingering effects. This is the first known AI-augmented nationally representative analysis of mortality and disparities for these associations. Methods: Quantum BAyesian Machine learning-augmented Propensity Score translational (QBAM-PS) statistics with multivariable regression was performed on the largest all payor US inpatient dataset, the National Inpatient Sample. Results: Of the 208,257,049 adult hospitalizations from 2016-2022, 124,954 (0.06%) had carcinoid tumors. Of the 71,402 hospitalizations with carcinoid from 2016-2019, 26,711 (37.41%) had metastases, 2,835 (3.97%) had acute heart failure, and 2,042 (2.86%) died. But of the 53,552 hospitalizations with carcinoid from 2020-2022, diagnosed metastases (38.04%) had increased, as did acute heart failure (4.21%) and mortality (3.73%), while 0.04% had diagnosed COVID. In all adult hospitalizations from 2016-2019 by QBAM-PS multivariable regression controlling for clinical confounders and severity, carcinoid and carcinoid syndrome did not significantly increase mortality, but carcinoid was significantly less likely to be diagnosed among Hispanics (OR 0.73) and Asians (OR 0.46) compared to Caucasians, in addition to Medicare (OR 0.71) and VA (OR 0.65) compared to private insurance, and more likely to be diagnosed in the highest versus lowest income quartile (OR 0.124) (all p<0.001). By 2020-2022, carcinoid and its syndrome did not significantly increase the odds of COVID diagnosis. But again carcinoid was significantly less likely to be diagnosed in Hispanics (OR 0.68), Asians (OR 0.61), Medicare (OR 0.78), and VA (OR 0.59), while the highest income again increased diagnosis odds (OR 1.19) (all p<0.01). There were no mortality disparities within carcinoid during either time period. Conclusions: This large multi-year analysis supports improvements in metastatic carcinoid detection and heart disease management, including through the COVID pandemic, though amid persistent racial, insurance, and income disparities.

Background: Atrial fibrillation (AF) significantly impacts quality of life (QoL) and is often observed in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Acoramidis achieves near-complete (≥90%) transthyretin (TTR) stabilization and is approved in the USA, the UK, Europe and Japan for the treatment of ATTR-CM in adults. In the phase 3 ATTRibute-CM study (NCT03860935), acoramidis treatment significantly reduced the time to all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) at Month 30, and resulted in improved 6-minute walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels relative to placebo. The clinical efficacy of acoramidis has not yet been reported in patients with ATTR-CM and with an AF or atrial flutter (AFL) diagnosis at baseline. Research Question: How does acoramidis treatment affect ACM or first CVH, 6MWD, KCCQ-OS scores, and NT-proBNP levels at Month 30 in participants with ATTR-CM with or without AF/AFL diagnosis at baseline? Methods: The ATTRibute-CM study design has been previously published. This post hoc analysis included participants in the modified intention-to-treat population (N=611) grouped by AF/AFL diagnosis at baseline (defined as recorded AF medical history or the presence of AF or AFL on an ECG at enrollment). The rate of ACM or first CVH at Month 30 was compared between groups using a stratified Cox proportional hazards model. Changes from baseline to Month 30 in 6MWD, KCCQ-OS scores and NT-proBNP levels were summarized descriptively. Results: Overall, 62.8% (384/611) of participants had an AF/AFL diagnosis at baseline (acoramidis: 255/409, placebo: 129/202). These participants had lower mean 6MWD and KCCQ-OS scores and higher median NT-proBNP levels than those without AF/AFL diagnosis at baseline. Treatment with acoramidis reduced ACM or first CVH, slowed the decline in 6MWD and KCCQ-OS scores and blunted the rise in NT-proBNP compared with placebo, regardless of AF/AFL diagnosis at baseline ( Table ). Conclusions: Acoramidis improved clinical outcomes (ACM, CVH), functional status, QoL and NT-proBNP levels relative to placebo in participants with ATTR-CM, regardless of AF/AFL diagnosis at baseline.

Background: Left atrial (LA) strain, measured by two-dimensional speckle tracking (2D-STE), has not been explored in lymphoma patients before anthracycline treatment as a prognostic marker for predicting future major adverse cardiovascular effects (MACE), heart failure, cardiotoxicity, and all-cause mortality after treatment. Hypothesis: Can an abnormal baseline LA peak reservoir strain (LA RS) measured before anthracycline chemotherapy predict MACE, heart failure, cardiotoxicity, and all-cause mortality in lymphoma patients? Methods: A retrospective cohort study was conducted including 104 patients diagnosed with Hodgkin and non-Hodgkin lymphoma, enrolled and followed from January 1, 2013, to June 30, 2023. LA RS was measured in a dedicated 4 chamber view (TomTec Imaging Systems, Unterschleissheim, Germany), abnormal values defined as less than 35%. Univariate Cox regression analyses were performed to assess whether the LA RS was associated with the development of MACE, cardiotoxicity, heart failure, and all-cause mortality. Multivariable Cox regression models were used to adjust for comorbidities. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression. Results: Among 104 patients (mean age of 59 years; [IQR], 49–70), 69 (66.3%) were male and 102 (98.1%) were white. MACE occurred in 19 patients, heart failure in 14 patients, and cardiotoxicity was observed in 4 patients. Additionally, all-cause mortality was found in 19 patients (18.3%). Abnormal LA RS was significantly associated with increased all-cause mortality (HR 3.12, 95% CI 1.02–9.53, p=0.0454) (Figure c), even after adjusting for hypertension, dyslipidemia, smoking status, gender and age (Figure d). No significant associations were found between LA RS and MACE (HR 1.42, 95% CI 0.56-3.62, p=0.4604) (Figure a), heart failure (HR 1.12, 95% CI 0.38-3.24, p=0.8299), or cardiotoxicity (HR 3.23, 95% CI 0.33-31.47, p=0.3128) (Figure b). Conclusions: Abnormal baseline LA strain measured by echocardiography is an independent predictor of all-cause mortality in lymphoma patients. These findings support the use of LA strain assessment into initial risk stratification protocols, providing particular value in identifying patients at increased risk of mortality.

Background: The efficacy of different conventional ventilation during automated head-up (AHUP) CPR using active decompression and impedance threshold device with head and torso elevation is unknown. We sought to determine the central and peripheral hemodynamics while using the 10:1 versus the 30:2 positive pressure ventilation (PPV). Research Question: Does the PPV delivery method affect the hemodynamics during AHUP-CPR? Methods: Ventricular fibrillation was induced in anesthetized pigs (n=5), followed by AHUP-CPR initiation with positive pressure ventilations applied using an automated bag compressor to deliver 10ml/kg of tidal volume over 1 sec at a rate of 10 breaths/min. After 15 minutes of CPR using a 10:1 ratio, ventilation was changed to a 30:2 ratio for 2 minutes with 2 PPV delivered consecutively. Thereafter 10:1 ratio was resumed followed by another 2-minute round of 30:2 PPV mode. Intraventricular pressures and volumes using conductance catheters placed in the right ventricle (RV), along with other hemodynamic parameters were recorded continuously, during the 2-minute intervals between PPV delivery. A mixed-effects model was used to evaluate the effects of PPV mode on pressure-volume (PV) loop parameters while using a Spearman correlation to explore the relationship between PV loop indices. Results: There was no statistically significant difference between RV stroke volume (SV) with 10:1 versus 30:2 PPV mode (Table 1). Throughout 2 minutes, 30:2 ventilation mode resulted in a significantly higher end-tidal CO2 (ETCO2), and higher pressures with a higher pulmonary elastance (Ea) imposed on RV (p<0.05). Higher Ea was strongly correlated with lower SV and ETCO2 (Spearman's rho correlation confidence of -0.97 and -0.83, respectively). No significant differences were observed between the two ventilation modes in any other hemodynamic parameters, including intrathoracic, aortic and right atrial pressures, as well as coronary and cerebral perfusion pressures. Conclusion: No significant difference was found for right ventricular stroke volume when comparing one breath after 10 chest compressions to two breaths after 30 compressions during automated head-up CPR. Delivering two consecutive breaths after 30 continuous compressions led to an overall higher ETCO2, but it also imposed greater ventricular pressure and afterload, which were significantly correlated with reduced SV and ETCO2.

Background: Etripamil nasal spray is a fast-acting, calcium channel blocker in development for the conversion of paroxysmal supraventricular tachycardia (PSVT) outside of a health-care setting. Studies have demonstrated the favorable safety and efficacy of self-administered etripamil in restoring sinus rhythm (SR) and reducing emergency department visits. Purpose: This report analyzes the efficacy, safety, and test-dose tolerability of etripamil across PSVT clinical studies. Methods: We systemically examined randomized, controlled and open-label trials evaluating etripamil in patients with PSVT. Efficacy measures included the proportion of patients converting from PSVT to SR within 30 minutes and the median times to conversion across all Phase 3 studies. Safety data for treatment-emergent adverse events (TEAEs), serious AEs, and test dose tolerability from Phase 2/3 studies were summarized descriptively. Results: NODE-1, NODE-301 Part 1, NODE-301 Part 2 (RAPID, including RAPID Extension, RAPID Open Label, RAPID Open Label Extension periods), NODE-302, and NODE-303 studies were analyzed (Table 1). The Kaplan-Meier estimate of etripamil exposed patients converting to SR within 30 minutes (n= 622) was 59.6% (range, 53.6% to 64.3%) with a median time to conversion of 18.5 minutes (95% CI, 15.7 to 21.0). The proportions of RCT placebo group patients converting from SVT to SR by 30 minutes ranged from 26.7% to 34.7%. Estimates of conversion of SVT to SR with etripamil at 60 minutes for individual studies ranged from 63.2% to 73.5% (Figure). Combined analysis showed mainly the occurrence of mild, transient TEAEs, primarily nasal discomfort, nasal congestion, rhinorrhea, throat irritation, and epistaxis (Table 2). 1,107 patients took at least one etripamil test dose while in SR; no significant change in average baseline heart rate or blood pressure was observed within 45 minutes of administration, and test dose failure occurred in only 16 patients (1.4%). Conclusions: Across multiple clinical studies of acute PSVT management, self-administered etripamil consistently demonstrated robust efficacy and a favorable safety profile for acute PSVT management. Safety data and the low rate of test dose failures indicate favorable tolerability, suggesting no need for a pretreatment test dose. These findings support the potential of etripamil as a patient-administered therapy for PSVT, which may reduce reliance on emergency care.

Introduction: Peripheral Arterial Disease (PAD) is a prevalent condition associated with considerable morbidity and mortality, a burden that is further intensified by the frequent co-occurrence of hypertension. The coexistence of these conditions not only amplifies cardiovascular risks but also complicates clinical management, thereby contributing to elevated mortality rates. Although their correlation is well understood, mortality trends in United States have not been studied. Methods: This study utilized International Classification of Diseases, 10th Revision (ICD-10) codes to extract age-adjusted mortality data for individuals with PAD and hypertension from the CDC WONDER (Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) cohort. The overall sample and subgroups defined by demographics (age, sex, race/ethnicity) and region (state, census and urban-rural status) were analyzed. Trends in mortality were quantified by computing associated annual percentage changes (APC) using Joinpoint Regression Program Version 4.9.0.0 trend analysis software. Results: A total of 540954 deaths were observed, of which 260517 were men (48.2%). Overall, the age-adjusted mortality rates (AAMR) exhibited a sharp increase from 1999 to 2001 (APC:25.3; 95% CI: -0.36,56.2), followed by a sustained decrease until 2017 (APC: -2.16; 95% CI: -11.1, -1.52), after which a notable upward trend was observed (APC:9.38; 95% CI: -0.38,24.1). A similar AAMR trend was seen on gender-based subgroup analysis with male patients showing the highest AAMR 13.5 (95% CI: 13.1,13.7) in 2020. Amongst all racial groups, Black or African American showed the highest 14.9 (95% CI: 14.8-15) while Asian or Pacific Islander showed the lowest 5.8 (95% CI: 5.7-5.9) AAMR over 2 decades. The West region had the highest overall age-adjusted mortality rate (AAMR) of 10.2 (95% CI: 10.2-10.3). Among individual states, Vermont displayed the highest AAMR, reaching 15.8 (95% CI: 15.1-16.5). Conclusion: Healthcare disparities are evident. The unprecedented recent increase in mortality rates, following years of successful decline, necessitates a thorough evaluation of healthcare policies and PAD treatment advancements to identify the causative factors behind this trend reversal.

Background: It is currently unknown whether patient engagement in adult congenital heart disease (CHD) care is influenced by social determinants of health (SDOH) such as race/ethnicity, education, and income. Adapting from the chronic care model, patient engagement, defined as the knowledge, skills, ability, and willingness to manage one’s health, can minimize lapses in care and improve CHD care outcomes. Methods: This cross-sectional study analyzes data from patients aged 18 and older with a self-reported diagnosis of CHD enrolled in a digital health research study called Empower My Congenital Heart. Patient engagement was measured using the Gothenburg Empowerment Scale (GES). We compared mean GES scores across demographic categories (race/ethnicity, education, and income), using independent samples t-tests or one-way ANOVA as appropriate. Additionally, we conducted a multivariate linear regression analysis to evaluate the impact of race/ethnicity, education, and income on GES scores, adjusting for age, gender, marital status, parental status, and employment status. Results: Of 323 adult CHD patients, the mean age was 45.6 ±15 years, 32.5% were males, 89.9% were non-Hispanic White, 29.7% had less than a Bachelor's degree, and 43.5% had less than $100,000 annual household income. The mean GES score was 61.8 ± 8, with significantly higher scores observed for non-Hispanic White identifying individuals (p=0.006) and those with a Bachelor's or higher level of education (p=0.005), while no difference across income levels (p = 0.394) (Figure 1). Linear regression analysis demonstrated that race and ethnicity remained significantly associated with GES scores (Table 1). Conclusions: Race/ethnicity and education level (in the bivariate analysis only), but not income, are the SDOH variables significantly associated with how empowered a CHD patient is in managing their health care. Future interventions that target enhancing patient engagement and self-management skills should take into consideration the influence of these demographic and social factors.

Introduction: Dyslipidemia remains a major driver of cardiovascular disease. Monoclonal antibodies (mAb) that block angiopoietin-like protein 3 (ANGPTL3) lower atherogenic lipids by a mechanism distinct from statins. Earlier evidence centred on the Evinacumab. A new trial now evaluate the investigational antibody SHR-1918. Hypothesis: We hypothesized that treatment with ANGPTL3 mAbs whether evinacumab or SHR-1918 would significantly improve lipid parameters compared to placebo without increasing adverse events. Aims: To Quantify the pooled effect of ANGPTL3 mAbs on low-density lipoprotein cholesterol (LDL-C), Triglycerides, apolipoprotein B (ApoB) and non-high-density lipoprotein cholesterol (non-HDL-C) and Compare efficacy and safety between Evinacumab and SHR-1918 subgroups. Methods: A systematic search of Pubmed, Google Scholar MEDLINE, Embase, and ClinicalTrials.gov untill 1 April 2025 was done and relevant randomised controlled trials (RCT's) comparing ANGPTL3 mAbs with placebo in dyslipidaemic patients were included. Data was extracted on spreadsheet and Data analysis was done in RevMan 5.4. Results: 5 RCT's comprising of 603 patients met inclusion criteria. The pooled analysis showed marked reductions in atherogenic lipids with ANGPTL3 monoclonal antibodies versus placebo, including low-density lipoprotein cholesterol (SMD = –2.73, 95 % CI –4.16 to –1.31, P < 0.001), triglycerides (SMD = –3.54, 95 % CI –4.71 to –2.37, P < 0.001), apolipoprotein B (SMD = –1.98, 95 % CI –2.97 to –1.00, P < 0.001) and non-HDL-C (SMD = –2.89, 95 % CI –4.00 to –1.78, P < 0.001). Sub-group analyses demonstrated directionally consistent lipid lowering for both evinacumab and the newer agent SHR-1918. Adverse-event due to treatment evaluation revealed no significant increase in Adverse events due to treatment (RR = 1.05, 95 % CI 0.87 to 1.27, P = 0.63) or serious events (RR = 1.37, 95 % CI 0.54 to 3.44, P = 0.49), indicating good overall tolerability. Conclusion: monoclonal antibodies targeting ANGPTL3 encompassing both evinacumab and the newer agent SHR-1918 consistently reduced LDL-C, triglycerides, and related lipid markers with a favourable tolerability profile. Further large, long-term studies are needed to fully establish their safety, clinical effectiveness, and potential to improve cardiovascular outcomes.