Citations

Abstract Disclosure: M. Kakakhel: None. M. Hussein: None. S. Fatima: None. F. Arshad: None. D. Rizwan: None. A. Qadeer: None. M. Khawar: None. R. Haider: None. S. Batool: None. H. Jawad: None. N.U. saleem: None. H. Ahmad: None. F. Ahmed: None. R. Kirchoff: None. R. Kirchoff: None. Background: With a global prevalence of 586,000 cases of thyroid cancer, thyroid cancer is the 10th most common malignancy. Despite advancements in early detection and treatment, the incidence of thyroid cancer continues to increase in the United States. This study aims to assess disparities in mortality trends stratified by age, sex, race, geography, urbanization status, and location of death, to guide clinical decision making. Methodology: Mortality data on thyroid cancer were extracted from the CDC-WONDER database, from 1999 to 2020. Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000 were stratified by age, sex, race, geography, urbanization status, and place of death. Joinpoint regression software was used to determine annual percent change (APC) and average APC. Results: From 1999 to 2020, a total of 46,777 deaths attributed to thyroid cancer occurred in the United States, among individuals aged ≥ 25 years. The overall AAMRs showed a positive trend, increasing from 0.6 per 100,000 (95% CI: 0.5-0.6) in 1999, to 0.7 (95% CI: 0.7 - 0.7) in 2020. 56.63% of those deaths, or 26,493 deaths, occurred in women. When stratified by age group, the 85+ age group had the highest CMR of 9 (95% CI: 8.3-9.7). The racial group with the highest AAMRs were Whites, with an AAMR of 0.7 per 100,000. Mortalities in the South region accounted for 33.5% of total deaths. Moreover, metro areas also had higher mortality rates than non-metro areas. Information regarding place of death was only available for 8242 deaths, with 2763 of them occurring in medical settings. Conclusion: Mortality rates in all population groups increased from 1999 to 2020, with variations in mortality rates noted among them. Risk stratification of high-risk groups, such as older people and women, and targeted interventions are key for addressing disparities in mortality rates. Presentation: Saturday, July 12, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. M.H. Alsaadi: None. M. Ikram: None. W. Ftih: None. H. Jawad: None. M.U. Rehman: None. R. Akhtar: None. A. Qadeer: None. M. Khawar: None. A. Ullah: None. H. Ahmad: None. F. Ahmed: None. R. Alcaraz: None. Introduction: Conditions that disrupt the adrenal glands' typical function are known as adrenal gland ailments or diseases. This study examines the distribution of adrenal disorders across various demographic and geographic groups in the United States, including gender, census region, race, age groups, and urbanization levels. Our objective was to identify disparities and trends to inform targeted interventions and resource allocation. Methods: From 1999 to 2020, mortality statistics for adrenal diseases were extracted from the CDC-WONDER database. Age, sex, race, location, urbanization status, and place of death were used to stratify the age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000. We calculated the average annual percentage change (APC) using Joinpoint regression software. Results: A total of 31,028 fatalities were reported due to adrenal disorders from 1999-2020 (AAPC: 1.277; 95% CI, -0.032 to 2.6032, p=0.055916). An initial rising trend was observed from 1999-2003 (APC: 2.4799), followed by a declining trend from 2003-2013 (APC: -3.0094), then a modest rise from 2013-2018 (APC: -0.9188), and finally a sharp increase from 2018-2020 (APC: 2.9445). Males had a higher AAMR (6.8) than females (6.4). The West census region had the highest AAMR (7.2), followed by the Midwest (7.1), South (6.3), and Northeast (5.6). The highest crude mortality rate was observed in individuals aged 85+ years (52.2). Several disparities were noted when stratified by urbanization and race, including the highest AAMR in Non Core (Nonmetro) regions (7.9) and among American Indian or Alaska Native populations (8.2). The highest percentage of deaths occurred in medical facilities. Conclusions: The findings underscore the need for tailored public health strategies to address disparities in adrenal disorders among vulnerable populations. Specific attention should be directed towards the male gender, West census region, American Indian or Alaska Native populations, and the geriatric population. Future research should explore underlying causes and interventions to mitigate these disparities. Presentation: Monday, July 14, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. S. Fatima: None. R. Noor: None. H. Javaid: None. P.K. Singh: None. H. Jawad: None. R. Haider: None. A. Qadeer: None. M. Khawar: None. T. Ashraf: None. F. Naveed: None. H. Ahmad: None. F. Ahmed: None. R. Kirchoff: None. Introduction: The health of a nation is often a reflection of the equity within its systems. Yet, when we examine the United States, one of the most developed nations globally, a concerning picture emerges in the realm of public health significant racial and ethnic disparities in disease outcomes. Among these, endocrine- related mortality, which includes conditions like diabetes, thyroid disorders, and hormonal imbalances, stands as a silent yet significant contributor to health inequities. Using data from the CDC WONDER database, this study seeks to explore these trends in depth, not just to identify the gaps but to shed light on the lived experiences of marginalized communities who bear the brunt of these inequities to pave the way for more equitable healthcare interventions. Methods: This descriptive study analyzes Racial and Ethnic Disparities in Endocrine-Related Mortality in the United States from 1999-2022, utilizing data from CDC Wonder database. We searched the Center for Disease Control database from 1999 to 2022 for mortality statistics with an underlying cause of death. The age-adjusted mortality rate (AAMR) was calculated per 1,000,000 deaths. We evaluated the AAMR using demographic variables such as race/ethnicity, geographic density, gender, age (25 or above), place of death, and the US Census Region. Temporal trends were assessed using Joinpoint regression software. Mortality rates by age, demographics, and place of death were examined. Statistical analysis calculated endocrine-related mortality rates and trends, with findings deemed significant at P < 0. 05. Results: Between the years 1999 to 2022, 837203 deaths were recorded to be caused by endocrine-related disorders. An overall rising mortality trend from 1999-2022 among all races and ethnicities is noted, except in Asian or Pacific Islander, Black or African American, and Hispanic patients, which shows a rise till 2020 followed by fall in age-adjusted mortality rates (AAMR) in 2022. A significant dip in mortality rate was seen in 2017 in all racial and ethnic groups. American Indian or Alaska Natives showed highest AAMR (181.87, 95% CI 178.06-185.69) followed by Black or African Americans (149.78, 95% CI 148.9-150.64), Hispanic or Latinos (112.33, 95% CI 111.59-113.07), Whites (94.31, 95% CI 66.6-68.25), Asian or Pacific Islanders (67.45, 95% CI 66.6-68.25). American Indians or Alaska Natives exhibit the steepest rise over time (APC -0.32 TO 8.85) from 1999-2022. Conclusions: Mortality due to endocrine-related disorders has dramatically increased over time. Significant disparities have been noted among different races and ethnic groups, with the highest rate among Americans and the lowest among Asians. This underscores the need for targeted interventions for specific racial groups to reduce the mortality burden of endocrine-related diseases. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Kakakhel: None. R. Haider: None. S. Cheema: None. S.M. Irshad: None. M.U. Hussain: None. A. Ullah: None. A.Z. Khan: None. F. Naveed: None. H. Jawad: None. F. Naveed: None. M.F. Hemida: None. A. Qadeer: None. M. Khawar: None. H. Ahmad: None. F. Ahmed: None. R.W. Kirchoff: None. R. Alcaraz: None. Background: Hypertension has been a significant cause of morbidity and mortality for ages. Coupled with endocrine disorders, it poses a greater risk of indisposition to the U.S population. This CDC wonder analysis explores the trends and patterns of these disorders, stratified by states and rural/urban. Methods: To attain this objective, this retrospective study has utilized data from the Center for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database to assess endocrine disorder-related mortality rates in the pediatric population from 1999 to 2011. Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) were used to evaluate trends and produce age-adjusted mortality rates (AAMRs) per 100,000 people. Data was stratified by year, sex, race/ethnicity, state-wise and geographical regions. Statistical significance and confidence intervals were used to assess the reliability of the observed trends. Results: Between 1999 and 2020, 2383332 deaths in the United States were attributed to endocrine-related mortality with underlying hypertension. The Overall AAMR initially rose steeply from 10.7 in 1999 to 24.9 in 2001 (APC: 34.3; 95% CI: 9.5 to 56.7), followed by a period of further steady increase in AAMR till 36.5 in 2018 (APC: 1.6; 95% CI: 0.6 to 2.1). This progressive increase in AAMR then sharply spiked from 2018 onwards, reaching 51.7 in 2020 (APC: 18.1*; 95% CI: 9.3 to 23.5). Notable discrepancies were observed in urbanization. Non-metropolitan areas showed a higher AAMR (35.5) than metropolitan (31.5). State-level analysis revealed substantial heterogeneity, including Mississippi as the state of the highest AAMR (58.6). Conclusion: The concerning rise of AAMR in non-metropolitan areas and Mississippi calls for more targeted health-care policies. These findings underscore the need for geographically tailored public health interventions to address disparities in endocrine disorder-related mortality in these groups. Presentation: Monday, July 14, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. M. Filal: None. A. Ullah: None. M.U. Hussain: None. M.A. Sadiq: None. T. Asghar: None. F. Arshad: None. N.K. Binashikhbubkr: None. H. Jawad: None. A. Abdullah: None. M. Qadri: None. A. Qadeer: None. M. Khawar: None. H. Ahmad: None. F. Ahmed: None. R. Alcaraz: None. Background: Hypertension is a major global health issue, affecting nearly half of U.S. adults. It is a leading risk factor for cardiovascular diseases like stroke, heart attack, and heart failure. Additionally, it is often linked to endocrine disorders, which can result in secondary hypertension. Endocrine disorders contributed to a concerning 2,383,332 deaths in the United States between 1999 and 2020, with many of these individuals having underlying hypertension. Methods: Death certificate data for adults aged 25 and older were obtained from the CDC-WONDER database. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMRs) per 100,000 individuals were computed. Temporal trends were analyzed by calculating the annual percent change (APC) and the average annual percent change (AAPC) in the rates using Joinpoint regression analysis. Results: The age-adjusted mortality rate (AAMR) rose sharply from 10.7 (95% CI:10.6-10.9) in 1999 to 24.9 (95% CI: 9.5 to 56.7) in 2001, then continued to increase steadily to 36.5 (95% CI: 0.6 to 2.1) by 2018. From 2018 onwards, the rate spiked significantly, reaching 51.7 (95% CI: 9.3 to 23.5) in 2020, which coincided with the COVID-19 pandemic. Men had higher overall AAMR i.e. 36.6 as compared to women 28.4 during the span of this study. Stratifying by race, Non-Hispanic Blacks or African Americans had the highest overall age-adjusted mortality rate at 64.4 vs non-Hispanic whites, who had the lowest rate at 27.6. Southern states exhibited the highest mortality rates among the census region followed by the Western, Midwestern, and Northeastern regions. In contrast, the Annual Mortality Rates (AAMRs) displayed similar patterns across all regions. Regarding age, people aged 85 and above had the highest mortality rate among all the age groups while ages 25-34 had the lowest. Conclusion: Endocrine disorders associated with underlying hypertension showed an increasing trend throughout the study period, peaking during the COVID-19 pandemic. These findings account for immediate targeted interventions directed at the most vulnerable demographic and geographical groups Presentation: Monday, July 14, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. F. Saleem: None. A. Ullah: None. M. Shah: None. A. Qadeer: None. M. Khawar: None. H. Jawad: None. H. Ahmad: None. F. Ahmed: None. S. N.l.: None. R. Alcaraz: None. Background: Diabetes mellitus (DM) is a global health burden, contributing significantly to mortality and comorbidities, including chronic kidney disease (CKD), which remains a leading cause of morbidity and mortality, especially in type 1 and type 2 diabetes. Methods: This retrospective cohort study examined mortality data from the United States from the CDC WONDER database, which gathers data from death certificates. Particularly, deaths from renal problems (ICD-10 codes E10.2-E14.2) linked to diabetes were the emphasis. Sex, age, race/ethnicity, and geographic location were among the important demographic factors that were used to stratify the data for the analysis. Temporal trends were examined using linear regression, while geographic disparities were assessed through chi-square tests and regression analysis. A significance level of p<0.05 was used for all tests. Results: According to the data, the death rate from diabetes increased significantly between 1999 and 2020. Between 1999 and 2020, the number of deaths from diabetes rose from 2,325 to 74,296. From 13.12 per 100,000 in 1999 to 276.92 per 100,000 in 2020, the age-adjusted death rate increased significantly, indicating a fivefold rise in mortality rates over the 21 years. After 2010, the pace of increase became especially steep, with notable yearly increases, especially in the years after 2013. In the Hispanic population alone, the number of deaths from diabetes more than quadrupled between 2013 and 2020, rising from 5,378 in 2013 to 10,395 in 2020. Male mortality rates were consistently greater than female death rates, indicating gender-based inequities as well. By 2020, there were 41,225 male deaths from diabetes (AAMR: 351.07). Notably, the death rate for men was almost 60% greater than that for women in 2020, with rates rising more sharply for men, particularly from 2010 onward. Significant differences in diabetes-related mortality were also observed by geography. Florida, Texas, and California had the largest mortality burdens; in California alone, 73,185 deaths, or 13.8% of all deaths, occurred. Lastly, more deaths were found to occur in medical facilities, especially inpatient settings, as well as at home or in hospice care, indicating a change in the place of death. Conclusions: The study shows a significant rise in diabetes-related mortality in the US over the past two decades, with males experiencing a higher mortality rate. Geographic disparities are also evident, with Southern states and large states like California, Texas, and Florida contributing disproportionately. The shift in death places suggests increased reliance on medical facilities, home care, and hospice care. The study calls for targeted public health interventions to address the growing burden of diabetes-related mortality, particularly in high-risk regions. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. F. Saleem: None. M.H. Alsaadi: None. H. Jawad: None. A.Z. Khan: None. A. Qadeer: None. M. Khawar: None. A. Ullah: None. M.F. Hemida: None. H. Ahmad: None. F. Ahmed: None. R. Alcaraz: None. Background: Globally, pediatric endocrine anomalies are a significant cause of early mortality. This study examines the discrepancies of paediatric endocrine abnormalities across various demographic and geographic groups in the United States, including gender, census region, race, age groups, and urbanization levels. Our objective was to identify disparities and trends to inform targeted interventions for the vulnerable demographics. Methods: Adhering to STROBES criteria, we extracted the mortality statistics due to endocrine disorders in the paediatric population from 1999-2020 from the Centre for Disease Control and Prevention-Wide Ranging Online Data for Epidemiologic research (CDC-WONDER). We calculated Age-Adjusted mortality rates (AAMRs) per 100,000 individuals. We calculated the Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC) to assess trends stratified by age, gender, urbanization, race, census region, and states. Joinpoint regression model was used for analysis. Results: Between 1999 and 2020, 5161 deaths among children less than 1 year to 14 years of age in the United States were related to endocrine-related disorders. Most occurred due to thyroid disorders, diabetes mellitus, and other miscellaneous disorders related to glucose regulation and pancreatic internal secretion. The overall AAPC for endocrine-related mortality in the pediatric population increased from 1.4866 in 2008 to 2.4982 in 2020, with an AAPC of 0.1346 (95% CI: -3.1216 to -3.5003, p > 0.000001). The male population had higher AAPCs than the female population (women: -0.9938; men: 0.7223). There were notable racial differences: The Hispanic or Latino population had the highest AAPC (0.15), followed by the Black population (-0.195) and then the White population with the lowest AAPC (-0.166). According to the age group stratification, the age group with the highest AAPC was the 5-14 age group (2.03) and the lowest the less than 1 year age group, with AAPC (-2.007). There was a significant decrease in deaths in the less than 1 year age group from 1999 to 2020 (p value < 0.05) with APC (-2.0) (95% CI: -3.0191 to -0.9861) and for the 5-14 age group from 2010 to 2020 with APC (10.8861) (95% CI: 3.4843 to 18.8). Depending on the urban-rural categorization, metro areas had a higher AAPC (0.1508) compared to the non-metro areas with an AAPC (-0.4467). Conclusion: The overall decline in endocrine-related deaths in the pediatric population from 1999 to 2020 hails an improvement in efforts made to manage these disorders. However, the recent uptick in the Hispanic-Latino population emphasizes the necessity for targeted efforts to tackle these disparities and improve the health outcomes of affected communities as well as in children 1-4 years of age, depicting the increased vulnerability and need for added care in this age group. Presentation: Saturday, July 12, 2025

Abstract Disclosure: M. Kakakhel: None. F. Saleem: None. A. Ullah: None. K. Abdul Rehman: None. M.H. Alsaadi: None. H. Ahmad: None. A. Qadeer: None. R. Haider: None. M. Khawar: None. H. Jawad: None. J. Ikram: None. M. Filal: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Thyroid disorders are common endocrine disorders including thyrotoxicosis, thyroiditis, hypothyroidism, and autoimmune thyroid diseases. Although it affects an estimated 200 million people globally, the epidemiology of this condition remains underexplored. Here we aimed to investigate mortality trends attributable to thyroid disorders in the US stratified by year, sex, race, and region. Methods: Using data from the CDC WONDER database, we calculated the crude and age-adjusted mortality rates (AAMRs) per 1,000,000 individuals (≥25 years) and used Joinpoint regression to determine annual and average annual percent change (AAPC) in the mortality trends. Results: Between 1999 and 2020, 561,089 deaths were recorded among patients with thyroid disorders in the United States, with an overall increasing trend in mortality (AAPC = 0.78). The age-adjusted mortality rate (AAMR) declined gradually from 1999 to 2018 (APC = -0.43, 95% CI: -0.65 to -0.22) before rising sharply from 2018 to 2020 (APC = 13.05, 95% CI: 6.39 to 20.12). Females had a higher AAMR (139.75) than males (81.99). Among racial and ethnic groups, Whites exhibited the highest AAMR (124.09), followed by American Indian or Alaskan Natives (121.36), Hispanics (89.13), Black or African Americans (88.44), and Asian or Pacific Islanders (59.36). Regional disparities showed the highest AAMR in the Midwest (130.45) and the lowest in the South (109.40). West Virginia (199.93) and North Dakota (198.82) reported the highest state-level AAMRs, while Nevada (60.18) and Florida (65.49) had the lowest. Non-metropolitan areas experienced higher mortality rates (141.04) than metropolitan areas (112.21), underscoring significant geographical and demographic variations in thyroid disorder-related mortality. Conclusion: Adults in the US have shown a rising trend in Thyroid-related deaths, with the highest mortality rates seen in females, Whites, and people living in the Midwest and Non-metropolitan areas. Our study also highlights the disparities across different demographics. Policy makers should focus on equitable access to healthcare to control this increasing mortality. Presentation: Monday, July 14, 2025

Abstract Background One in five adults aged 40 will develop heart failure (HF) during their lifetime. Risk factors (e.g., hypertension, diabetes mellitus, coronary artery disease, etc.) lead to structural and functional changes in cardiomyocytes, resulting in HF. At the cellular level, these changes consist of mis/over‐expression of genes that regulate cardiac identity (e.g., CamK2δ, PKC, Stat3, etc.). The current paradigm for treating HF is pharmacological or device‐based intervention; however, with few exceptions, the condition worsens with time. We are proposing to implement a change in HF treatment, shifting from a drug‐centric system to a cardiac target‐specific molecular approach that would reverse hypertrophy and adverse remodelling of affected cardiomyocytes. Methods A cardiomyocyte targeting peptide (CTP) was reversibly linked to miRNA106a for delivery to a mouse model of HF. Reversal of morphological, signalling, and physiological HF parameters was measured. Additionally, CTP‐miRNA106a was introduced into a human cardiomyocyte cell line to identify mechanism(s) at play for reversing HF characteristics (e.g., hypertrophy). Results Bio‐distribution studies showed that intravenously injected CTP‐miRNA106 delivered its cargo specifically to the heart within 30 min, followed by clearance of CTP from the heart to the kidneys, and to a lesser extent, the liver by 35 h with persistence of miRNA106a in cardiomyocytes until day 7 (the latest tested time‐point). CTP‐miRNA106a reversed angiotensin2/isoproterenol‐induced hypertrophy in 90% of the treated mice. We also identified two potential HF intracellular signalling pathways/mechanisms (PLCβ1/PKC/IP3 and NF‐κB) targeted by CTP‐miRNA106a that could benefit many pathophysiologies underlying HF, including inflammation. Conclusions CTP‐miRNA106a, a first‐of‐a‐kind cardiac‐specific drug, downregulates genes involved in cardiac hypertrophy and inflammation through the PLCβ1 and CamKIIδ kinase pathways. CTP delivery of miRNA106a cargo is specific to cardiomyocytes both in vitro and in vivo, and once delivered, many HF parameters, including hypertrophy, are reversed. Key points Cardiac Targeting Peptide (CTP) delivers, specifically to the heart, reversibly linked miRNA106a. MiRNA106a targets genes in various pathways known to cause heart failure when they are over/hyper activated returning their expression to normal levels. In vivo analyses using a mouse heart failure model resulted in reversal of heart failure parameters in 19/20 mice.