Citations

Abstract Disclosure: H. Ahmad: None. S. Fatima: None. M. Kakakhel: None. I. khan: None. A. Raza: None. Z. Khan: None. R. Haider: None. A. Qadeer: None. M. Khawar: None. F. Ullah: None. H. Jawad: None. J. Ikram: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Type 1 diabetes mellitus (T1DM) is an autoimmune condition, characterized by the destruction of pancreatic beta cells, resulting in lifelong dependency on insulin. It is a significant health burden in adolescents and young adults, with long-term complications affecting quality of life and survival. We aim to explore sex-stratified trends in mortality and disability-adjusted life years (DALYs) due to T1DM from 1990 to 2021. Methods: We obtained sex-stratified data for adolescents and young adults (15-39 years) with T1DM from the Global Burden of Disease (GBD) from 1990 to 2021. The mortality rates were age-standardized and expressed per 100,000 deaths. Trends were analyzed as annual percentage change (APC) and average APC (AAPC) using Joinpoint Regression. Results: From 1990 to 2021, deaths due to T1DM in adolescent and young adult males increased globally from 7,123 to 9,244 per annum, with age-standardized mortality rates (ASMRs) decreasing from 0.64 to 0.61 and standardized DALYs rising from 49.56 to 51. In females, deaths rose from 6,160 to 6,892, with ASMRs declining from 0.57 to 0.47 and DALYs declining from 47.12 to 43.11. Despite the apparent rise in deaths, ASMRs exhibited a significant decline in both sexes, with an AAPC of -0.16% (95% CI: -0.20 to -0.12) in males and -0.62% (-0.68 to -0.55) in females, four times that of in males. The DALYs showed a significant decline in females with an AAPC of -0.31% (-0.35 to -0.26) but a significant increase in males with an AAPC of 0.09% (0.04 to 0.12). Males showed the greatest APC increase in ASMRs of 1.34% from 1990 to 1994, while females showed the greatest APC increase of 0.45% from 1990 to 2000, three times less and over twice the period seen in males. This was followed by the greatest APC decline of -1.14% in females from 2001 to 2011, and a non-significant decline of -0.14% till 2021. Males experienced the greatest decline of -1.14% from 2000 to 2013. It then increased significantly from 2013 to 2018 (APC: 0.73%), followed by a significant decline of -0.62% till 2021, almost four times that in females. DALYs showed a similar trend in females with the greatest increase of 0.45% from 1990 to 2000, followed by the greatest decrease of -1.14% till 2011, and then a non-significant decline of -0.14 till 2021. Males showed the greatest increase of 1.24% from 1990 to 1994 and the greatest decrease of 0.63% from 2000 to 2013, followed by a much smaller decline. Conclusion: Although ASMRs declined, the recent decline in ASMRs in females is becoming less pronounced highlighting the importance of ongoing monitoring and improvement strategies. The disparity in DALYs between males and females also demands the need for targeted interventions addressing male-specific challenges to reduce the burden of T1DM. Presentation: Sunday, July 13, 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. 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: R. Haider: None. M. Waqas: None. S. Khan: None. A. Ullah: None. M. Khawar: None. A. Qadeer: None. M. Talha: None. A. Batool: None. A. Khan: None. M.Z. Haider: None. R.W. Kirchoff: None. Background: Hypothyroidism and heart failure (HF) contribute significantly to mortality among older adults. Understanding mortality trends, including demographic, geographic, and socio-economic disparities, is crucial to inform healthcare policies and resource allocation. Methods: This study analyzed age adjusted mortality rates (AAMRs) from 1999 to 2022 for adults aged 55-85+ years. Age adjusted mortality rates (AMRs) per 1,000,000 population were stratified by gender, race, geographic location, and urbanicity. Trends were evaluated using Average Annual Percentage Change (APC) with 95% confidence intervals (CI), examining periods of decline and increase. Results: Between 1999 and 2022, 105,008 deaths were recorded among older adults (55-85+ years) due to hypothyroidism and heart failure (HF). The age-adjusted mortality rate (AAMR) initially declined from 1999 to 2016, marked by a significant drop between 2005 and 2008 (APC = -6.0, 95% CI: -7.6 to -3.0). However, mortality trends reversed post-2016, with a sharp increase (APC = 6.7, 95% CI: 5.5 to 8.4). Age-specific trends revealed declining crude mortality rates (CMR) across all groups until 2016, followed by increases, particularly in the 65-74 and 75-84 age brackets, with APCs of 14.1 (95% CI: 7.8 to 27.8) and 8.9 (95% CI: 3.8 to 21.8), respectively. Gender disparities showed men and women had similar trends, with declines until 2015-2016 followed by surges, with APCs of 6.8 (95% CI: 5.2 to 9.1) and 6.6 (95% CI: 4.6 to 11.1), respectively. Racial disparities highlighted steady declines until 2016, followed by increases in non-Hispanic Whites (APC = 10.4, 95% CI: 5.2 to 23.2) and Hispanics (APC = 7.5, 95% CI: 6.0 to 10.1). Geographically, the Midwest exhibited the highest AAMR (71.1), while the Northeast showed the lowest (51.4). State-level disparities revealed North Dakota with the highest AAMR (129.5), contrasting with Nevada, which had the lowest (20.4). Urban-rural differences showed similar trends, with notable AAMR increases in both settings post-2016. These results underscore significant demographic and regional disparities in hypothyroidism and HF-related mortality. Conclusion: While mortality from hypothyroidism and HF among older adults declined until 2016, trends have since reversed across all demographic and geographic strata. Addressing these rising rates require targeted interventions focusing on high-risk groups and areas. 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 The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood. Here, we report a new regulatory link between HELLS and single-strand break (SSB) repair in cellular responses to DNA alkylation damage. We found that loss of HELLS impairs SSB repair and selectively sensitizes cells to DNA alkylating agents and PARP inhibitors (PARPi). Our data reveal non-epistatic interactions between HELLS and PARP1 and suggest that HELLS functionally compensates for PARP1 deficiency in promoting cell survival in response to DNA alkylation damage. Furthermore, we found that HELLS is co-expressed with PARP1 in cancer cells, and its loss is synthetic lethal with homologous recombination deficiency (HRD). This work unveils new functions of HELLS in modulating SSB repair and responses to clinically relevant DNA alkylation damage, thus offering new insights into the potential therapeutic value of targeting HELLS in cancer.

Introduction In moderate to high-risk surgical procedures, 15–25% of patients develop a postoperative surgical site infection. Intraoperative incisional wound irrigation has the potential to reduce surgical site infections, and additional randomised controlled trials are required to provide evidence of effectiveness. Methods and analysis This protocol describes a pragmatic, adaptive, participant and adjudicator-blinded trial at 13 sites in Canada in up to 2500 participants. Participants planned for surgery with an abdominal or groin incision, who are eligible and provide verbal consent through an integrated consent model, are randomised to receive intraoperative incisional wound irrigation with povidone-iodine, saline or no irrigation. The primary outcome is surgical site infection within 30 days postoperatively. Secondary outcomes include quality of life measured 30 days postoperatively and morbidity, mortality and healthcare utilisation within 90 days postoperatively. Ethics and dissemination This trial has been approved by the research ethics board at the participating centres and stopped enrolling participants on May 23, 2025. All participants will provide verbal consent. Results will be disseminated via presentation at conferences, publication and posted on clinicaltrials.gov. Trial registration number The study is registered with http://clinicaltrial.gov ( NCT04548661 ; 14 September 2020).