Citations

Background: Cochlear implantation (CI) is a transformative intervention for adolescents with severe-to-profound sensorineural hearing loss, offering benefits that extend beyond auditory rehabilitation to encompass psychosocial and functional outcomes. Despite growing global evidence, there is limited data on the impact of CIs on quality of life (QoL) in low- and middle-income settings, particularly from the adolescent’s perspective. Objective: To evaluate the quality of life of adolescents with unilateral cochlear implants and to assess the influence of demographic and contextual factors on perceived QoL outcomes in a Pakistani cohort. Methods: In this cross-sectional study, 110 adolescents aged 10–19 years with at least 12 months of unilateral CI use were recruited from four rehabilitation centers in Lahore, Pakistan. Participants completed the Glasgow Benefit Inventory (GBI) and a structured demographic questionnaire. Descriptive statistics and inferential analyses compared GBI scores across gender, implant side, and educational placement, with significance set at p < 0.05. Results: The mean GBI total score was 38.6 (SD 11.4), with significant improvements observed across general, social support, and physical health domains (all p < 0.001). No statistically significant differences were found in QoL outcomes by gender, side of implantation, or school type. Strong associations were observed between general well-being and social support. Conclusion: Unilateral cochlear implantation yields substantial, multidimensional quality-of-life benefits for adolescents, independent of demographic or educational context. Integration of psychosocial support and inclusive practices is essential for maximizing post-implant outcomes.

e16076 Background: Gastric cancer is the fourth leading cause of global cancer deaths. Despite declining incidence and mortality, it remains a significant contributor to the global disease burden. This study analyzes regional gastric cancer DALYs and mortality trends from 1990-2021 using the GBD database. Methods: The regional DALYs and mortality rates per 100,000 individuals aged 70+ from GBD 2021 were analyzed, with trends from 1990 to 2021 evaluated using AAPC, and statistical significance assessed by p-values. Results: In 2021, the greatest Age-standardized DALYs rates were recorded in Andean Latin America, with 3068.04 per 100,000; the lowest was found in High-income North America with 386.08 per 100,000. The most significant increase of DALYs rate from 1990 to 2021 was in Southern Sub-Saharan Africa, (AAPC = -0.3068%; 95% CI: -0.3852 to -0.2234; p < 0.000001), while in Western Europe, the largest decline was noted (AAPC = -2.9999%; 95% CI: -3.0164 to -2.9841; p < 0.000001). Andean Latin America was the region with the highest Age-standardized mortality rates (ASMRs) in 2021, at 207.58 per 100,000 while High-income North America had the lowest at 27.18 per 100,000. In Western Sub-Saharan Africa, the ASMRs were rising with an AAPC of -0.2601% (95% CI: -0.2872 to -0.2368; p < 0.000001), while Western Europe had the highest decline with an AAPC of -2.7658% (95% CI: -2.7895 to -2.7471; p < 0.000001). Conclusions: The global burden of diseases from 1990 to 2021 is regional in nature. In 2021, DALYs and mortality were predominantly high in Andean Latin America and East Asia and notably low in High-income North America. DALYs have risen across Southern Sub-Saharan Africa over three decades, and mortality increased over Western Sub-Saharan Africa, while both declined sharply in Western Europe. These trends underscore the importance of regionalized health solutions. DALY per 100,000. Metric Region 1990 2021 AAPC (1990-2021) HIGHEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PER 100,000 Andean Latin America 4469.23 3068.04 -1.14 East Asia 5507.72 2958.98 -1.99 High Income Asia Pacific 4849.23 2130.43 -2.71 LOWEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PER 100,000 High Income North America 758.59 386.09 -2.22 Australasia 1116.91 567.32 -2.16 South Asia 794.81 680.50 -0.46 HIGHEST MORTALITY RATE PER 100,000 Andean Latin America 293.65 207.58 -1.04 East Asia 324.60 188.92 -1.72 High Income Asia Pacific 316.44 161.94 -2.22 LOWEST MORTALITY RATE PER 100,000 High Income North America 51.24 27.19 -2.02 Australasia 74.36 41.81 -1.85 South Asia 47.50 41.95 -0.39

e16456 Background: Gastric cancer is one of the significant contributors of mortality and morbidity, especially in older patients. Analyzing national trends in the Disability adjust life years (DALY) helps identify the evolving burden of this disease among patients older than 70 years and highlights the regions requiring particular interventions. Methods: Using Global burden of disease data from 2021, national DALY rates per 100,000 people aged 70 and over with gastric cancer were assessed. The Estimated Annual Percentage Change (EAPCs) with p value taken as a statistical measure of significance, was used to evaluate trends from 1990 to 2021. Results: The analysis displays considerable contrasts in the trends of gastric cancer burden across nations. From 1990 to 2021, a rising trend in DALY EAPC was seen in Egypt (1.01883; 95% CI: -0.1931- 1.958) followed by Honduras (0.3262; 95% CI: 0.0177- 0.7456) and Lesotho (0.2253; 95% CI:-0.1326- 0.6995). Conversely, Austria (-0.7368; 95% CI: -0.7646 to -0.7087), Republic of Korea (-0.7095; 95% CI: -0.7620 to -0.6442) and Singapore (-0.6923; 95% CI: -0.7286 to -0.6553) reported a prominent decline in DALY EAPCs, reflecting significant progress in reducing burden. The DALY rates in 2021 also varied dramatically among nations. Highest DALY rate was observed in Bolivia (4882.7; 95% CI:3782.9- 6349.7) underscoring highest impact on healthcare system. Conversely, Morocco (329.69; 95% CI: 234.64- 410.12) recorded lowest DALY rate indicating comparatively better disease control or lower incidence. Conclusions: While some nations demonstrate remarkable progress in mitigating the burden of gastric cancer, others still face significant challenges. Highest increase in EAPC in Egypt, Honduras and Lesotho whereas significant decline in Austria, Korea, and Singapore indicates areas of target public health efforts. Future research should focus on understanding the causes of these disparities and evaluating the impact of interventions across it. DALY and EPAC. Country 2021 DALY rate EAPC(1990-2021) EAPC, 95% CI Egypt 1272.146 1.018834(highest) -0.193 to 1.959 Honduras 2880.563 0.32617 0.018 to 0.746 Lesotho 1555.79 0.225384 -0.133 to 0.699 Singapore 806.6098 -0.692396 -0.729 to -0.655 Republic of Korea 1961.151 -0.709502 -0.762 to -0.644 Austria 662.5105 -0.736826(lowest) -0.765 to -0.709 Morocco 410.1227(lowest) -0.17817 -0.387 to 0.097 Bolivia 4882.718(highest) -0.32185 -0.473 to -0.103

e16419 Background: Pancreatic cancer remains one of the most lethal malignancies worldwide. While high-income regions have long faced higher rates, recent trends show that lower-income regions are also beginning to see an increase. This study explores how pancreatic cancer incidence and prevalence have changed over the past 30 years among adults aged 70 and older assessing regional differences. Methods: We analyzed data from the Global Burden of Disease (GBD) spanning three decades (1990–2021) to assess pancreatic cancer incidence and prevalence rates among adults aged 70+. Data focused on different regions worldwide, grouping them by income levels using the Socio-demographic Index (SDI) and annual changes in incidence and prevalence rates were calculated. Results: In 2021, High-income Asia Pacific had the highest incidence rate at 119.52 per 100,000, whereas Low SDI regions had the lowest at 12.01 per 100,000. High-income regions accounted for the majority of cases, with over 140,000 reported, compared to fewer than 3,000 in the lowest-income areas. Andean Latin America experienced significant APC fluctuations, with a sharp rise from 2015 to 2019 followed by a decline, while High-income North America saw a recent decrease in incidence. Overall, most regions exhibit a steady increase in pancreatic cancer prevalence, with higher AAPCs in Sub-Saharan Africa, North Africa, and parts of Asia, while high-income regions show more moderate increases. Trend analysis reveals significant trends in pancreatic cancer incidence and prevalence among individuals aged 70+. Western Sub-Saharan Africa has the highest Average Annual Percent Change (AAPC) at 2.3248%, indicating the most substantial increase in prevalence from 1990 to 2021, followed by North Africa and the Middle East at 1.9906%. Low-middle SDI regions also show a steady rise with an AAPC of 1.718%, while high-income regions like High-income Asia Pacific report a notable AAPC of 1.595%. Conclusions: Our findings show a concerning rise in pancreatic cancer among older adults, with the most dramatic increases in regions like Western Sub-Saharan Africa and North Africa. To tackle this growing challenge, we need focused efforts on prevention, early detection, and accessible care, especially in lower-resource settings. Incidence percent changes. Metric Region 1990 2021 AAPC (1990-2021) Highest incidence percent change Western Sub-Saharan Africa 7.62 15.38 2.31 North Africa and Middle East 20.97 37.23 1.91 Lowest incidence percent change Caribbean 41.51 41.36 -0.016 Southern Latin America 74.05 73.89 0.006 Highest prevalence percent change Western Sub-Saharan Africa 4.54 9.21 2.32 North Africa and Middle East 12.49 22.77 1.99 Lowest prevalence rate percent change Caribbean 25.02 25.38 0.02 Southern Latin America 44.78 45.45 0.06

e16418 Background: Pancreatic cancer remains one of the most fatal malignancies globally, posing a significant burden on older populations. Despite numerous reports on its prevalence, a detailed comparative analysis of national trends among adults aged 70 and older from 1990 to 2021 is scarce. This study seeks to bridge this gap by evaluating prevalence rates using data from the Global Burden of Disease (GBD) study. Methods: Prevalence data for pancreatic cancer in individuals aged 70 years and older were obtained from the GBD-2021 dataset, encompassing 204 countries and territories for the years 1990 and 2021. The Estimated Annual Percent Change (EAPC) and corresponding 95% confidence intervals (CI) were calculated to assess trends over the period from 1990 to 2021. Results: The prevalence of pancreatic cancer has shown a significant increase since 1990, reaching its highest levels in 2021. In 1990, the United States of America (USA) reported the highest prevalence, followed by Japan and China. However, by 2021, Japan ranked first in prevalence, followed by China and the USA. The analysis revealed that in 1990, the highest prevalence rates of pancreatic cancer were observed in Greenland (91.04 per 100,000), followed by Finland (82.57 per 100,000) and Japan (76.30 per 100,000). By 2021, Japan reported the highest prevalence (126.73 per 100,000), followed by Finland (119.20 per 100,000) and Canada (109.22 per 100,000). Despite the observed prevalence rates from 1990 to 2021, Turkmenistan exhibited the most significant increase (EAPC: 15.41, 95% CI: 10.91, 21.41), followed by the Republic of Cabo Verde (EAPC: 13.61, 95% CI: 8.67, 19.59) and Mongolia (EAPC: 4.81, 95% CI: 3.11, 7.20). In contrast, the most significant declines were recorded in the Republic of San Marino (EAPC: -0.308, 95% CI: -0.51, -0.03), followed by Guam (EAPC: -0.24, 95% CI: -0.37, -0.08) and Cuba (EAPC: -0.21, 95% CI: -0.33, -0.09). Conclusions: The prevalence of pancreatic cancer among adults aged 70 and older has increased significantly over the past three decades, with distinct regional patterns. Countries like Japan, China, and the USA continue to report the highest prevalence rates. These findings highlight the urgent need for targeted prevention, screening, and treatment strategies, particularly in high-burden regions, to mitigate the growing impact of pancreatic cancer in aging populations. Prevalence percent changes. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) Highest prevalence percent change Turkmenistan 0.62 10.16 15.41 (10.91, 21.41) Republic of Cabo Verde 3.23 47.18 13.61 (8.67, 19.59) Mongolia 5.25 30.53 4.81 (3.11, 7.20) Lowest prevalence percent change Republic of San Marino 52.61 36.36 -0.308 (-0.51, -0.03) Guam 16.96 12.87 -0.24 (-0.37, -0.08) Cuba 32.65 25.52 -0.21 (-0.33, -0.09)

e22572 Background: Pancreatic cancer is a highly lethal malignancy that disproportionately impacts older populations, contributing significantly to global disease burden. Disability-adjusted life years (DALY) serve as a comprehensive metric to quantify the combined impact of mortality and morbidity. This analysis of the Global Burden of Disease Study-2021 (GBD-2021) aims to characterize trends in DALY rates attributable to pancreatic cancer among individuals aged 70 years and older across 204 nations. Methods: Data on DALY associated with pancreatic cancer for individuals aged 70+ were extracted for 204 nations from the GBD-2021 study for the years 1990 and 2021. Estimated annual percent change (EAPC) with 95% confidence intervals (CI) were calculated from 1990 to 2021. Results: The DALY rates were accessed among individuals aged 75 and older diagnosed with pancreatic cancer. In 1990, Greenland exhibited the highest DALY rate globally (2825.65), but by 2021, this position was surpassed by the United Arab Emirates (2775.52), with Greenland declining to the second-highest rate (2082.43). On the other hand, Turkmenistan had the lowest DALY rates in 1990, but by 2021, Mozambique had taken this position, with Turkmenistan ranking 170th. Despite the observed DALY rates from 1990 to 2021, Turkmenistan experienced the highest change (EAPC: 15.23, 95% CI: 10.88–21.18), followed by the Republic of Cabo Verde (EAPC: 12.88, 95% CI: 8.14–18.75) and Mongolia (EAPC: 4.53, 95% CI: 2.90–6.88). A decrease in DALY was observed in over 24 nations, with the Republic of San Marino recording the largest decline (EAPC: -0.37, 95% CI: -0.55, -0.12), followed by Bermuda (EAPC: -0.26, 95% CI: -0.43, 0.03) and Greenland (EAPC: -0.26, 95% CI: -0.45, -0.009). Conclusions: From 1990 to 2021, DALY rates related to pancreatic cancer among individuals aged 70 and older rose worldwide, particularly in Turkmenistan, the Republic of Cabo Verde, and Mongolia. There is a pressing need for global adoption of screening programs to enable early detection and treatment of these cases. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) HIGHEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PERCENT CHANGE Turkmenistan 19.66 319.09 15.22 (10.88–21.18) Republic of Cabo Verde 98.12 1361.76 12.88 (8.14–18.75) Mongolia 172.14 952.05 4.53 (2.90–6.88) LOWEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PERCENT CHANGE Republic of San Marino 1323.96 834.01 -0.37 (-0.55, -0.12) Bermuda 1696.97 1249.11 -0.26 (-0.43, 0.03) Greenland 2825.66 2082.43 -0.26 (-0.45, -0.009)

Abstract Background While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown. Methods Aptamer-based proteomics was performed on 147 CSF samples from 74 patients; 71 of whom had grade 2–4 astrocytomas or grade 2–3 oligodendrogliomas. This included pre- versus post-resection intracranial CSF samples obtained at early (1–16 days; n = 20 patients) or delayed (86–153 days; n = 11 patients) time points for patients with glioma. Paired lumbar versus intracranial glioma CSF samples were also obtained (n = 14 patients). Results Significant differences were identified in the CSF proteome between lumbar, subarachnoid, and ventricular CSF in patients with gliomas. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome, with distinct sets of proteins present at different time points since resection. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, such as bevacizumab and immunotherapies. Conclusions The intracranial glioma CSF proteome serves as a rich and dynamic reservoir of potential biomarkers that can be used to evaluate the effects of resection and other therapies over time. All data within this study, including detailed individual clinical annotations, are shared as a resource for the neuro-oncology community to collectively address these unanswered questions and further understand glioma biology through CSF proteomics.

Background: Transthyretin cardiac amyloidosis (ATTR-CA) carries an elevated risk of developing ventricular arrhythmias (VA) but there remains limited evidence supporting the role of catheter ablation in this population. Purpose: To assess the safety and efficacy of catheter ablation for VA in ATTR-CA. Methods: An electronic database was used to identify all patients suspected of having ATTR-CA who underwent catheter ablation for VA at our institution between January 2010 and December 2023. Patients who did not meet the diagnosis of ATTR-CA and had a negative workup who underwent catheter ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) were used to form a control group matched for age, sex and left ventricular ejection fraction at a ratio of 2:1. Results: 20 controls and 10 cases of ATTR-CA were identified. Examining the two groups at baseline (Table 1), the mean age at index ablation was 67.7±7.0 and 68.6±8.1 years (p=0.359), mean follow-up time was 4.1±3.1 and 4.2±2.6 years (p=0.494), and the proportion of males was 100% and 90% respectively. The ATTR-CA group had a significantly higher proportion of chronic kidney disease (90% vs. 50%, p=0.032) and prior stroke or thrombotic events compared to the control group (50% vs. 10%, p=0.026) with similar CHA 2 DS 2 VASc scores (4.2±1.6 vs. 3.8±1.3, p=0.233). Both groups had comparable left ventricular ejection fraction (41.4%±14% vs. 46.9%±15.2%, p=0.173), VT/PVCs at presentation (40%/60% vs. 25%/75%, p=0.77), use of antiarrhythmics (70% vs. 60%, p=0.592), and high proportion of atrial fibrillation/flutter (70% vs. 90%, p=0.168). Procedural (261.2±101.2 vs. 265.7±125.6 mins, p=0.449) and total energy delivery time (1442.9±1509.1 vs. 1744.6±956.2 secs, p=0.296) was not significantly different in the two groups. Both groups had a significant decrease in PVC burden postablation with a reduction from 26.8% to 3.8% (p=0.024) and from 27.1% to 13.6% (p=0.028) in the ATTR-CA and control group respectively. A downward trend was seen in antitachycardia pacing events for VT postablation in the ATTR-CA (14.7±9.8 vs. 5.3±6.7, p =0.184) and control (193±387.6 vs. 0.67±1.2. p=0.139) groups. No major complications occurred after ablation (Table 2). Mean time to recurrence post-index ablation was similar between both groups (1620.4±483.8 vs. 1498.8±291.4 days, p=0.987, Figure 1). Conclusions: Catheter ablation appears to be safe and effective for VT and PVCs in patients with ATTR-CA.

Abstract Aims Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT. Methods and results A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0–2), intermediate (3–5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome. Conclusion Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE.

e23536 Background: Circulating tumor DNA (ctDNA) has gained prominence as a potential indirect marker for minimal residual disease (MRD) in various cancers, including soft tissue sarcomas (STS). Previous studies have suggested that indirect hematologic ratios – such as Neutrophil-Lymphocyte Ratio (NLR), Monocyte-Lymphocyte Ratio (MLR), Platelet-Lymphocyte Ratio (PLR), and Eosinophil-Lymphocyte Ratio (ELR) may correlate with worse outcomes. We sought to evaluate the correlation of NLR, MLR, PLR and ELR in a real world cohort of Non-Hispanic Whites (NHW) and Hispanics (H) with advanced STS. Methods: We performed a retrospective chart review at Dignity Health Cancer institute using our Electronic Medical Records (EMR) and Signatera™ assay to obtain our data points. Inclusion criteria were STS patients of all ages and stages of disease with complete records. We reviewed 33 patient charts, 14 NHW and 19 H patients. Of the NHW population, 11 were male (M) and 3 females (F). For the H population, 14 were M, and 5 were F. We utilized Spearman's rank correlation coefficient to assess monotonic relationships between ct-DNA levels and the hematologic ratios. ct-DNA was quantified through standardized assays per Protocol, with the resultant values treated as continuous variables in our statistical analyses. Power considerations, based on expected effect sizes and type I error rate adjustments were performed. Results: The Spearman’s correlation coefficients and p-values indicated varied associations across ethnic groups. For NHW, the correlations were generally weak and non-significant (NLR: r = 0.18, p = 0.54; MLR: r = -0.04, p = 0.89; PLR: r = 0.35, p = 0.21; ELR: r = 0.001, p = 1.00). Conversely, in the Hispanic cohort, stronger and statistically significant correlations were observed, particularly with NLR (r = 0.78, p < 0.0001) and MLR (r = 0.70, p < 0.001). Overall, the correlations across the entire study population did not reach statistical significance. Conclusions: This study revealed notable racial variations, particularly in the H population, in the relationship between ctDNA levels and hematologic ratios. The noteworthy associations found with NLR (r = 0.78, p < 0.0001) and MLR (r = 0.70, p < 0.001) highlight the possible usefulness of these ctDNA and these indirect biomarkers in assessing disease status in STS. These findings suggest the possibility of using hematologic ratios, particularly in the Hispanic population, as markers of disease progression similar as ctDNA. Hematologic ratios are more easily accessible to the general population compared to ctDNA in many underserved countries and communities. Future studies with larger cohorts are need to further analyze its validity.