Citations

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)

e16481 Background: Gastric cancer is a malignant disease characterized by the uncontrolled growth of cells in the stomach lining. It is a global health concern with regional variation in incidence and prevalence. This study investigates the regional incidence and prevalence of gastric cancer among adults aged 70 and older from 1990 to 2021, utilizing data from 26 global regions. Methods: Global Burden of Disease (GBD) data for 2021 were analyzed to assess regional incidence and prevalence of gastric cancer among adults aged ≥ 70. The Annual Average Percentage Change (AAPC) was calculated to evaluate trends from 1990 to 2021, with statistical significance determined using p-values. Results: In 2021, East Asia has the highest incidence (273403) followed by Middle SDI (189383) and High-middle SDI (176691). Highest Prevalence numbers were recorded for East Asia (398,000) followed by High SDI (337,000) and High-middle SDI (250,000). With regards to rates per 100,000, Oceania has the lowest incidence (257) as well as prevalence (252) followed by Central Sub-Saharan Africa (I:1142 , P: 1081) and Southern Sub-Saharan Africa (I:1295, P: 1227). The largest increase in AAPC of incidence was exhibited by Western Sub Saharan Africa (-0.24, CI: -0.27 to -0.23), Southern Sub Saharan Africa (-0.29, CI: 0.37 to -0.22), and South Asia (-0.306, CI: -0.422 to -0.158) regions, while South Asia (-0.087, CI: -0.1748 to 0.0308), East Asia (-0.0952, CI: 0.0284 to 0.1606), and Andean Latin America (-0.1696, CI: -0.3498 to -0.0381) showed largest increase in AAPC of prevalence. Western Europe region had the greatest decline in AAPC of incidence (-2.3995, CI: -2.4374 to -2.3691) followed by Central Europe (-2.2010, CI: -2.3007 to -2.1445) and Eastern Europe (-2.1554, CI: -2.212 to -2.0925 ) regions while Central Asia had the greatest decline in AAPC of prevalence (-1.9281, CI: -2.0109 to -1.8522) followed by High Income Asia Pacific (-1.8268, CI: -1.8926 to -1.7913) and Eastern Europe (-1.8103, CI: -1.8631 to -1.7623). All AAPC values were statistically significant (p < 0.000001). Conclusions: The East Asia region exhibited the highest incidence and prevalence, highlighting the vulnerability of these populations, while Central Sub-Saharan Africa bore the least burden. Notably, several regions, particularly in Asia, experienced substantial increases in both incidence and prevalence, emphasizing the need for targeted interventions. Conversely, some regions, such as Europe, showed encouraging declines in prevalence, suggesting that effective prevention and control strategies can be implemented. These findings underscore the importance of tailored approaches to address the evolving burden of Gastric Cancer.

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)

e22570 Background: Aging into the seventh decade of life marks a pivotal shift in cancer susceptibility, with pancreatic cancer (PC) emerging as one of the most relentless threats to global health. This study utilizes three decades of Global Burden of Disease (GBD) data to unravel unprecedented insights into the prevalence and incidence of PC among adults aged 70 and older. Methods: We analyzed data from the GBD study to assess the temporal trends in the incidence and prevalence of PC from 1990 to 2021. The Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC), along with 95% confidence intervals (CI), were utilized to assess the overall trends, with statistical significance evaluated using p-values. Results: Over the past three decades, the global burden of PC has surged significantly. In 1990, the global incidence of PC stood at 45.12 per 100,000, escalating to 54.47 per 100,000 by 2021. Likewise, global prevalence increased from 30.33 per 100,000 in 1990 to 40.60 per 100,000 in 2021, with incidence rates consistently exceeding prevalence, suggesting an accelerating number of new cases of PC worldwide. The AAPC analysis revealed a significant upward trajectory in both global incidence (AAPC: 0.6085, 95% CI: 0.5801, 0.6273 p < 0.000001) and prevalence (AAPC: 0.9467, 95% CI: 0.9188, 0.9659 p < 0.000001) of PC. Following the APC analysis, several notable trends emerged. The global incidence of PC experienced its most substantial increase between 2003 and 2010 (APC: 1.0806, 95% CI: 0.9817, 1.3206 p < 0.000001), while the slowest growth in incidence occurred from 1990 to 2003 (APC: 95% CI: 0.9817, 1.3206 p = 0.000400). Conversely, the global prevalence of pancreatic cancer saw its most pronounced rise between 1998 and 2001 (APC: 2.0389, 95% CI: 1.2005, 2.1962 p < 0.000001), with the slowest increase occurring from 1994 to 1998 (APC: 0.4632, 95% CI: 0.2544, 1.9767 p = 0.001200). Conclusions: The persistent rise in both incidence and prevalence of PC over the past three decades underscores a critical global health challenge, with a marked acceleration in recent years. These findings highlight the urgent need for targeted interventions and a deeper understanding of the factors driving this expanding burden, particularly as the incidence consistently outpaces prevalence. Metric Overall 1990 2021 AAPC with 95% CI (1990-2021) INCIDENCE RATES PER 100,000 Global Incidence 45.12 54.47 0.61 (0.58, 0.63) PREVALENCE RATES PER 100,000 Global Prevalence 30.33 40.60 0.95 (0.92, 0.97)

Abstract Colony stimulating factor-1 receptor (CSF1R) encodes for a tyrosine kinase receptor expressed on microglia. CSF1R related disorder is a devastating autosomal dominant leukoencephalopathy caused by CSF1R with variable penetrance in adults. It remains significantly underdiagnosed or misdiagnosed. We report a case of a 43-year-old woman with an insidious onset of neurocognitive decline, alien limb phenomenon, and personality changes over 1 year. In this report we will discuss the clinical approach, differential diagnosis, investigation, and available treatment options for CSF1R related disorder.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Despite ongoing efforts to employ structure-based methods to discover targeted protein degraders (TPD), the prevailing strategy remains synthesizing a focused set of heterobifunctional compounds and screening them for target protein degradation.

AbstractObjectiveTo describe the phenotypes, oncological associations, biomarker profiles, and outcomes across different age groups in patients with ANNA1 (anti‐Hu) autoimmunity.MethodsA retrospective review of patients with ANNA1‐IgG in serum/CSF between January 1, 2001, and December 31,2019 was performed. Patients were classified into three groups based on the age of symptom onset. Phage immunoprecipitation sequencing (PhIP‐Seq) and neurofilament light chain (NfL) measurements were done in patient sera/CSF with archived samples.ResultsOf 122 patients, 81 (66%), 20 (16%), and 21 (17%) patients belonged to older adults, young adults, and pediatric groups, respectively. Lung cancer and neuromuscular presentations were more common in older adults (p < 0.001), while limbic encephalitis and neuroblastoma were more common in pediatric patients (p < 0.005). Most young adults (75%) did not have cancer identified. Proportions of patients with a favorable response to immunotherapy were 20%, 30%, and 52% among older adults, young adults, and pediatric groups, respectively. PhIP‐Seq demonstrated significant enrichment for ELAVL4 peptides especially for amino acids 240–289, in the majority of samples evaluated (36/67, 54%). ZIC and SOX2 peptides were significantly enriched in those with central nervous system presentations. Serum NfL levels were elevated in patients with cancer and those with poor long‐term outcomes.InterpretationYoung adults with ANNA1 autoimmunity phenotypically resembled older adults but rarely had an underlying cancer. Pediatric patients frequently presented with limbic encephalitis and neuroblastoma and often responded favorably to immunotherapy. Distinct antigenic signatures may underlie differences in clinical presentations. Serum NfL levels may be a biomarker of poor long‐term outcomes in ANNA1 autoimmunity.