Citations

Background: Cocaine use and cardiovascular disease (CVD)-related mortality trends in the U.S. are underreported. Using the CDC’s Wide-Ranging Online Data for Epidemiologic Research database, we analyzed the relationship between cocaine use and CVD-related deaths. Methods: We analyzed death certificates from the Multiple Cause of Death dataset to identify CVD-related deaths involving cocaine use. Age-adjusted mortality rates (AAMRs) per 1 000 000 and annual percentage changes (APCs) were calculated using Joinpoint Regression. Results: From 1999 to 2022, 82 944 deaths were linked to cocaine use and CVDs. AAMRs rose from 9.6 in 1999 to 32 in 2022. Mortality trends varied by demographics and regions. Males and females showed early increases (1999–2006), declines (2006–2012), and sharp rises (2012–2022), with APCs of 11.8% and 12.8%, respectively. Non-Hispanic Black individuals exhibited consistently higher rates than non-Hispanic Whites, though both groups experienced sharp increases starting in 2014 (APCs: 12.5 and 12.7%). Geographic trends revealed early 2000s increases, mid-2000s declines, and rapid rises beginning in the 2010s. The Northeast and South had notable APCs of 13.5 and 12.6% (2013–2022). Rural areas initially showed steeper increases than urban areas but displayed steady upward trends since 2011 (APC: 9.5%). Age-wise, older adults experienced a particularly sharp rise from 2012 to 2022 (APC: 15.0%). Conclusion: Cocaine use and CVD-related mortality rose significantly from 1999 to 2022, with pronounced increases among men, non-Hispanic Black individuals, older adults, urban residents, and those in the South. These findings highlight a growing public health crisis.

e17594 Background: Cardiovascular disease (CVD) is the leading cause of death among women with ovarian cancer. This study investigates cardiovascular mortality in women with ovarian cancer across the United States, assessing trends by geography and urbanization. Methods: Mortality data from the CDC WONDER database (1999–2020) were analyzed. Females with ovarian cancer listed on the death certificate and cardiovascular disease as the cause of death were identified using ICD-10 codes. Age-adjusted mortality rates (per 100,000) were calculated and stratified by census region and urbanization. Trends were evaluated using Average Annual Percent Change (AAPC) calculated by the Joinpoint Regression Program V5.4.0. Results: From 1999 to 2018, cardiovascular mortality in ovarian cancer patients declined, with an APC of –2.09%, consistent across regions and urbanization levels. However, from 2018 to 2020, a concerning reversal occurred, with mortality increasing by +3.79% per year. The abrupt rise in mortality is observed in the Midwest region, with an APC of +3.99, and in small and medium metro regions, with APCs of +7.38 and +6.46, respectively. This reversal in cardiovascular mortality in ovarian cancer from 2018 to 2020 is likely due to the COVID-19 pandemic that disrupted screening and treatment. Conclusions: This 21-year analysis demonstrates a long-term decline in cardiovascular mortality among women with ovarian cancer, followed by a sharp reversal from 2018 to 2020. This increase suggests the urgent need for public health interventions to reduce cardiovascular risk among ovarian cancer patients.

e17524 Background: Cervical cancer remains one of the leading causes of female cancer mortality, while heart failure drives chronic disease burden. Their coexistence complicates outcomes through shared risk factors, cardiotoxicity, and mortality. This study examined cervical cancer mortality trends in patients with heart failure, assessed disparities, and aimed to inform integrated management strategies. Methods: We analyzed death certificates from CDC WONDER Database (1999–2020), using ICD-10 C53 (cervical cancer) and I50 (heart failure). Female mortality was stratified by race and urbanization. Joinpoint Regression Program V5.4.0 calculated Annual Percent Change (APC) and Average Annual Percent Change (AAPC). Results: A total of 5,534 deaths were identified. Age-adjusted mortality rates (AAMR) declined overall, but trends varied. Among females, mortality fell from 0.1102 per 100,000 in 1999 to 0.076 in 2020 (AAPC -1.28%). Three phases emerged: a modest decline (1999-2006, APC -1.45%), a rapid decline (2006-2009, APC -17.6%), and a concerning reversal (2009-2020, APC +3.27%). The latter increase may reflect reduced screening, declining vaccination rates, or COVID-19 disruptions.By urbanization, large central metropolitan areas showed a steady decline (APC -4.13%). By race, White women demonstrated a consistent reduction (APC -2.61%), indicating sustained benefits of screening and vaccination. Conclusions: Cervical cancer mortality in heart failure patients declined from 1999-2020, reflecting prevention and healthcare advances. However, disparities persist, with notable increases among women since 2009. These findings highlight successes but stress the urgent need for vaccination and screening.

e17104 Background: Prostate cancer is a commonly diagnosed malignancy among men. Sepsis continues to pose a significant threat to outcomes. Patients with are particularly vulnerable to sepsis due to immunosuppression from the malignancy itself, advanced age, and treatment-related factors including catheter use. Sepsis is associated with high short-term mortality, and worsened overall outcomes, underscoring the need for epidemiological and clinical evaluation. Methods: We analyzed death certificates from 1990-2023 from CDC Wonder Database. We used ICD-10 codes, C61 for malignant neoplasm of prostate and C56 for sepsis to identify related deaths. Mortality rates were compared by urbanization, sex and census region. Joinpoint Regression Program V5.4.0 computed Annual Percent Change with 95% CIs. p value < 0.05 was considered statistically significant. Results: Between 1999 and 2023, 39,801 deaths were recorded. Overall age-adjusted mortality rates (AAMRs) changed little over time, remaining near 2 deaths per 100,000 population (2.02 in 1999 and 2.00 in the most recent year). Clear differences were seen across demographic groups.In 1999, AAMRs among Black or African American was highest with value of 6.80 compared to white and hispanic or latino individual with AAMR vales 1.67 and 1.89 respectively.In 2023, mortality among Black individuals fell to 5.06; however, rates were still higher than those seen among White (1.76) and Hispanic/Latino (1.92) populations. Geographic differences were also evident.The mortality rate in the South, decreasing from 2.43 in 1999 to 2.16 in 2023, was highest among all the other census regions.Mortality rates declined across both metropolitan and nonmetropolitan areas, falling from 2.02 to 1.84 in metropolitan regions and from 2.05 to 1.73 in nonmetropolitan regions in year 2020. Conclusions: Overall sepsis-related mortality has remained relatively unchanged over the two decades, with significant racial and geographic disparities. Black individuals continue to experience disproportionately higher mortality, and Southern region showed consistently elevated rates. Both metropolitan and non-metropolitan areas saw modest declines. These findings highlight the continued need for targeted preventive measures and management strategies to reduce mortality and improve outcomes. Prostate cancer with sepsis AAMRs. variable AAMR 1999 AAMR 2023 Overall / Male 2.02 (1.91-2.14) 2.00 (1.92-2.09) Race Black or African American 6.80 (6.04-7.56) 5.06 (4.60-5.53) White 1.67 (1.56-1.78) 1.76 (1.67-1.85) Hispanic or Latino 1.89 (1.39-2.50) 1.92 (1.65-2.20) Census Region Northeast 2.25 (2.00-2.51) 1.99 (1.80-2.18) Midwest 1.71 (1.50-1.92) 1.65 (1.49-1.81) South 2.43 (2.22-2.63) 2.16 (2.02-2.30) West 1.54 (1.33-1.76) 2.12 (1.94-2.30) Urbanization AAMR 2020 Metro 2.02 (1.90-2.15) 1.84 (1.75-1.93) Non-metro 2.05 (1.79-2.30) 1.73 (1.54-1.92)

e16067 Background: Gastric carcinoma remains a significant cause of cancer mortality in the United States. Although overall mortality rates have declined, persistent disparities exist across racial, age, and geographic groups. For cancer patients, sepsis—a life-threatening infection response—is a major fatal complication. Analyzing linked mortality data is crucial for identifying high-risk populations, understanding the burden of cancer-associated infections, and guiding targeted prevention and treatment strategies to improve outcomes and achieve health. Methods: This cross-sectional study used CDC WONDER mortality data from 1999–2020 for adults aged 25 years and older. Causes of death were identified using ICD-10 codes, and age-adjusted mortality rates (AAMRs) were calculated across sex, race/ethnicity, age, census regions, and urban–rural categories. Mortality trends were assessed using Joinpoint regression to estimate average annual percentage changes (AAPC) with 95% confidence intervals (CIs) and statistical significance. Results: From 1999 to 2020, U.S. stomach cancer mortality declined overall, with AAMRs decreasing from 0.29 to 0.22 per 100,000 (AAPC = –0.8%, 95% CI: –1.64 to 0.04). Significant declines occurred among adults aged 65–74 (APC = –1.7%, 95% CI: –2.32 to –1.05), 75–84 (APC = –1.9%, 95% CI: –2.65 to –1.05), and ≥85 years (APC = –3.0%, 95% CI: –4.02 to –1.99). Adults 45–54 years experienced increasing mortality after 2005 (APC = 5.1%, 95% CI: 2.82 to 7.46), while rates among 55–64 years remained stable. Male mortality declined significantly (AAPC = –1.24%, 95% CI: –1.93 to –0.54), whereas female mortality showed no significant long term change (AAPC = –0.93%, 95% CI: –2.44 to 0.60). Black (AAPC = –2.25%, 95% CI: –3.02 to –1.47) and Hispanic/Latino populations (AAPC = –1.50%, 95% CI: –2.26 to –0.74) experienced significant declines. Regionally, the Northeast showed the largest decline (AAPC = –2.30%, 95% CI: –3.52 to –1.07), while the Midwest, South, and West demonstrated no significant long term trends. Metropolitan areas declined from 1999–2011 (APC = –2.80%, 95% CI: –4.44 to –1.14). Conclusions: While overall U.S. gastric cancer mortality declined from 1999–2020, this progress is uneven. Significant increases among adults aged 45–54 and stable rates for those 55–64 highlight an emerging concern. Furthermore, declining trends are concentrated in specific demographic groups and regions, such as the Northeast, revealing persistent disparities. These findings underscore the need for targeted prevention and research focused on younger adults and lagging geographic areas.

Background Patients with substance use disorder (SUD) have high rates of hospitalization, readmission, and prolonged lengths of stay. Objectives To conduct a systematic review and meta-analysis of the impact of addiction consult services in the inpatient setting for patients with SUD. Methods Five databases were systematically searched from their earliest available records through January 2025. Two authors independently screened articles, extracted data, and assessed the quality of each study with the Newcastle-Ottawa Scale for observational studies and the Cochrane risk-of-bias tool for randomized clinical trials. Pooled odds ratios (ORs) with 95% CIs were calculated for dichotomous outcomes, and mean differences were calculated for continuous outcomes. Results The search retrieved 20 studies that met inclusion criteria. The intervention for all studies was an addiction medicine consult, but the definition of this consult varied. The meta-analysis did not detect statistically significant differences in hospital length of stay, hospital readmission, or emergency department visits at 1 year among patients who received the consult compared with those who did not; however, many of these outcomes were likely underpowered. However, addiction medicine consults significantly improved the odds of inpatient initiation of medication for SUD (OR, 7.30; 95% CI, 3.30-16.13; P <.001) and postdischarge SUD treatment linkage and adherence (OR, 3.31; 95% CI, 2.06-5.32; P <.001). Conclusion Inpatient addiction consult services are associated with increased inpatient initiation of medication for SUD treatment and postdischarge treatment linkage and adherence. No clear association was identified between the consult and readmissions, emergency department utilization, or length of stay.

Abstract Medulloblastoma (MB) is one of the most prevalent malignant brain tumors in children, with tremendous cognitive and neuroendocrine disability among survivors. Group 3 (G3) MBs have poor overall survival at &lt; 50%, higher frequency of metastasis, and no targeted therapies. Amplification of MYC and activation of TGFβ signaling are frequent in G3MB. Remarkably, some tumors have no reported mutations, suggesting roles for epigenetic mechanisms in driving disease. We have generated novel humanized models for G3MB by transducing neuroepithelial stem cells (NESC) derived from human induced pluripotent stem (iPSC) cells with TGFβ effectors alone and/or in combination with MYC, prioritizing combinations observed in patients. We determined that both MYC and TGFβ effectors drove tumor formation in vivo with the combination driving more aggressive tumors and higher frequency of metastasis. NESC-derived tumors clustered with human G3/G4MB, indicating our models recapitulated human disease. To decipher mechanisms of resistance, we integrated CUT&RUN for MYC genomic localization and histone PTMs with RNA-sequencing and discovered MYC-bound neural developmental genes repressed in MYC and TGFβR1-driven lines. Further interrogation identified JARID1B, a MYC binding partner, as a regulator of many of these repressed neural genes. We postulate that deregulation of MYC and context-specific targeting to the chromatin template culminates in transcriptional alterations that promote aggressive G3MB. To further investigating therapeutic vulnerabilities, we have performed a in vivo whole genome CRISPRi screen to reveal important drivers of malignancy, one of the first of it’s kind in brain tumors. We are functionally validating key candidate sgRNAs that were differentially significant in primary tumors and may also have key roles in driving metastasis. Excitingly, many sgRNAs identified from the screen were chromatin modifiers and may be important co-factors of MYC-mediated regulation on the epigenome. Collectively, our studies provide a critical framework for understanding mechanisms of resistance and the epigenetic landscape of MYC- and TGFβ-driven MB.

Abstract Background Valvular heart disease (VHD) and atrial fibrillation (AF) frequently coexist, presenting complex clinical challenges despite advances in diagnostics and therapeutics. Together, they contribute substantially to cardiovascular mortality. However, epidemiological patterns vary across demographics and regions Methods Mortality data from 1999–2023 were obtained from the CDC WONDER database. Deaths attributed to VHD (ICD-10: I30-I52) with co-diagnosed AF (ICD-10: I48) among adults ≥ 45 were included. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated. Autoregressive integrated moving average (ARIMA) models were used to project mortality trends through 2035. Results From 1999 to 2023, there were 172,511 VHD and Afib-related deaths in adults ≥ 45. AAMRs increased until 2021, followed by a slight decline to 8.86. The overall AAPC for VHD with AF was 4.01%. AAMR increase was consistent across all age groups, highest seen in 65 + individuals. Males had consistently higher AAMRs than females. AAPC for males was 4.44% and for females 3.52%. Non- Hispanic White had the highest AAMR (10.56 in 2021), followed by Hispanics (4.19). Regionally, the West had the highest AAMR (11.27), followed by Mid-West (9.94). Non-metropolitan areas had higher AAMR 8.96 compared to metropolitan areas (AAMR: 7.59). Most VHD related deaths were reported in inpatient settings (n = 396,451) and 12% involved co-diagnosed AF. Conclusion Mortality associated with VHD and AF in the U.S population aged ≥ 45 has shown a concerning increase. Predictive models indicate this trend may persist, highlighting the need for early detection, equitable healthcare access and public health interventions tailored to high-risk populations.

ABSTRACT Background Lung cancer (LC) and respiratory failure (RF) are leading causes of adult mortality worldwide. Analyzing long‐term mortality trends across demographic, racial, geographic, and socioeconomic groups is essential to address disparities and enhance outcomes. This study investigates US national mortality patterns for LC and RF from 1999 to 2023, focusing on changes in age‐adjusted mortality rates (AAMRs) and key disparities. Methods Mortality data from the CDC WONDER database (1999–2023) for adults aged 25+ with LC (ICD‐10: C34) or RF (ICD‐10: J96) were analyzed. AAMRs per 100,000 were calculated, stratified by gender, race/ethnicity, region, state, and urban–rural status. Temporal trends were assessed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs), with significance at p < 0.05. Results Over 1999–2023, 456,325 deaths from LC and RF were recorded. AAMRs declined from 1999 to 2010 (APC = −1.2, 95% CI: −1.6 to −0.9) but rose from 2010 to 2023 (APC = 1.4, 95% CI: 1.1–1.7). Men's AAMRs steadily decreased, whereas women's dropped initially, then increased from 2011 to 2023 (APC = 2.0, 95% CI: 1.7 to 2.5). Non‐Hispanic Whites saw a sharp AAMR rise from 2014 to 2017 (APC = 2.7, 95% CI: 0.9 to 3.3), with other racial/ethnic groups showing mixed trends. Regionally, the Northeast had the highest AAMRs (8.6, 95% CI: 8.5 to 8.7), and the Midwest the lowest (7.1, 95% CI: 7.0 to 7.1). Metropolitan areas saw increases post‐2006, whereas nonmetropolitan areas rose after 2009 (APC = 2.3, 95% CI: 1.8–3.1). Mississippi had the highest state AAMR (14.0, 95% CI: 13.7–14.4), Wisconsin the lowest (3.7, 95% CI: 3.5–3.8). Conclusion LC and RF mortality declined until 2010, then increased, revealing significant disparities. Targeted interventions are critical to address these trends and reduce inequities.

Abstract Medulloblastoma (MB) is one of the most prevalent malignant brain tumors in children, with tremendous cognitive and neuroendocrine disability among survivors. Group 3 (G3) MBs have poor overall survival at &lt;50%, higher frequency of metastasis, and no targeted therapies. Amplification of MYC and activation of TGFβ signaling are frequent in G3MB. Remarkably, some tumors have no reported mutations, suggesting roles for chromatin-driven mechanisms in this disease. We have generated novel humanized models for G3MB by transducing neuroepithelial stem cells (NESC) derived from human induced pluripotent stem cells with TGFβ effectors alone and/or in combination with MYC, prioritizing combinations observed in patients. We determined that both MYC and TGFβ effectors drove tumor formation in vivo with the combination driving more aggressive tumors and higher frequency of metastasis. Importantly, NESC-derived tumors clustered with human G3MB, indicating our models recapitulated human disease. To decipher mechanisms of resistance, we integrated CUT&RUN for MYC genomic localization and histone PTMs with RNA-sequencing and discovered MYC-bound neural developmental genes repressed in MYC and TGFβR1-driven lines. These gene signatures were associated with the Polycomb Repressive Complex (PRC) and demarcated with H3K27me3; the histone mark directly regulated by PRC. Further interrogation identified JARID1B, a MYC binding partner and H3K4me3 demethylase, as a regulator of these repressed neural genes. This is further reinforced by the observation of higher H3K27me3 levels concurrent with increased JARID1B expression in human G3MB patient samples, compared to other subtypes. We postulate that deregulation of MYC and context-specific targeting to the chromatin template culminates in transcriptional alterations that promote aggressive G3MB. These studies support a critical role of MYC in repressing target genes to drive tumor formation and JARID1B as a new target for therapy. Collectively, we present a critical framework for understanding mechanisms of resistance and the chromatin landscape of MYC- and TGFβ-driven G3MB.