Citations

130 Background: The COVID-19 pandemic markedly affected the U.S. health care system and may have altered the diagnosis and management of pancreatic cancer. We examined national trends in pancreatic cancer diagnoses before and throughout the first two years after the onset of COVID-19 in the United States, using the latest data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We queried the SEER database for cases of pancreatic cancer diagnosed between 2019 and 2021 using ICD-O-3 codes C25.0-C25.9. Disease stage was categorised as localised, regional, distant, or unknown according to the SEER combined summary staging system. Case counts and incidence rates were compared across 2019, 2020, and 2021, with year-to-year differences assessed for statistical significance using χ² tests. Results: The overall number of cases of PDAC diagnosed in 2019, 2020, and 2021 (including year-to-year changes) were 13,457, 13,153 (-2.3%, p<0.05), and 13,998 (+6.4%, p<0.001). Among the known SEER summary staging for PDAC, 52.3% of cases were categorised as “distant” at the time of diagnosis in 2019, compared to 53.6% (+2.4%, p<0.05) in 2020, and 52.0% (-2.8%, p<0.05) in 2021. This reflected an overall change of -0.5% in “distant” PDAC diagnoses from 2019 to 2021 (p>0.05). Conclusions: Significantly fewer cases of PDAC were diagnosed in 2020 compared with 2019, followed by a significant increase in 2021 to above pre-pandemic levels. The proportion diagnosed as distant was significantly higher in 2020 than in 2019 but did not differ significantly between 2019 and 2021. These findings suggest a transient shift toward more advanced-stage PDAC diagnoses during the first year of the COVID-19 pandemic with likely delays in diagnosis, which returned to baseline in 2021.

129 Background: Pancreatic ductal adenocarcinoma (PDAC) presents with significant morbidity and mortality. Five-year survival at 13% consistently remains among the lowest of all cancers. We undertook a population-level risk analysis of sociodemographic risk factors (sex, age, ethnic, and geographic) that may inform closer monitoring of those with increased likelihood of developing PDAC. Methods: PDAC incidence data from 2000 to 2022 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, representing approximately 37% of the US population. Age-adjusted incidence rates (AAIRs) were calculated by race, sex, age group, and county-level rural–urban classification. Incidence is reported per 100,000 population. Temporal trends were assessed using annual percent change (APC) estimated via weighted least-squares regression. Results: Between 2000 and 2022, the overall AAIR of PDAC was 12.6. Incidence was highest among Black individuals (16.1), followed by White (12.7) and Hispanic (11.7) individuals, and was consistently higher in males (14.3) than in females (11.2). Temporal trends did not differ significantly by sex, with annual increases of +0.8% in males and +0.9% in females. Incidence increased progressively with age across all racial and ethnic groups in both sexes. While overall incidence was comparable between urban and rural counties, rural counties experienced a significantly faster rise in incidence (+1.3% vs. +0.8% APC; p<0.05). Conclusions: PDAC incidence has increased from 2000 to 2022 across both sexes at all ages and across all ethnicities. Those most at risk include males and Black individuals, with rates rising faster in rural counties. Better epidemiological understanding of developing trends of at-risk patients may inform screening strategies for patients at high risk of developing PDAC. Incidence rate (per 100,000 population) and annual change in PDAC (95% CI with Tiwari modification). Rate Trend Sex Male 14.3 (14.2-14.4) 0.8 (0.7-0.9) Female 11.2 (11.1-11.3) 0.9 (0.8-1.0) Age 40-44 years 2.7 (2.6-2.8) 1.3 (0.8-1.8) 45-49 years 5.6 (5.4-5.8) 0.8 (0.5-1.1) 50-54 years 10.9 (10.8-11.1) 0.6 (0.4-0.9) 55-59 years 19.2 (19.0-19.5) 1.0 (0.7-1.3) 60-64 years 30.8 (30.0-31.1) 0.8 (0.5-1.0) 65-69 years 45.9 (45.0-46.4) 0.9 (0.7-1.0) 70-74 years 62.2 (62.0-62.8) 0.8 (0.6-0.9) 75-79 years 79.7 (79.0-80.6) 1.0 (0.8-1.2) 80-84 years 94.7 (94.0-95.8) 0.9 (0.7-1.1) 85-89 years 104.6 (103-106.1) 0.8 (0.5-1.1) 90+ years 101.7 (100-103.6) 0.4 (0.1-0.8) Race White 12.7 (12.6-12.8) 1.1 (1.0-1.2) Black 16.1 (16-16.3) 0.3 (0.2-0.5) American Indian/Alaska Native 10.5 (10.0-11.1) 1.4 (0.4-2.4) Asian or Pacific Islander 10.2 (10.0-10.4) 0.6 (0.4-0.8) Hispanic 11.7 (11.5-11.8) 0.7 (0.4-0.9) Location Urban 12.6 (12.5-12.7) 0.8 (0.7-0.9) Rural 12.6 (12-12.7) 1.3 (1-1.5)

Background Primary aldosteronism (PA), a renin-independent state of aldosterone excess, is associated with excess risk of stroke, myocardial infarction, atrial fibrillation, heart failure, and chronic kidney disease compared with essential hypertension. Emerging evidence suggests that renin-independent aldosterone excess exists on a continuum rather than as a dichotomous disease state, including subclinical primary aldosteronism (sPA), even in normotensive individuals. Whether sPA is associated with major adverse cardiovascular events (MACE) prior to overt hypertension remains incompletely characterized. Objective To synthesize available evidence linking renin suppression and mild aldosterone excess to cardiovascular outcomes. Methods A narrative review of the literature was conducted using PubMed/MEDLINE, the Cochrane Library, and Web of Science from inception through May 2025, to identify cohort studies evaluating renin phenotype, aldosterone levels, and cardiovascular outcomes. Results Suppressed renin and higher aldosterone levels, even within conventionally normal ranges, are associated with incident hypertension, left ventricular hypertrophy (LVH), atrial fibrillation, and cardiovascular events. In overt PA, significantly higher rates of cardiovascular diseases have been observed compared with blood pressure-matched essential hypertension. Emerging population-based data suggest a graded cardiovascular risk extending below traditional diagnostic thresholds. Conclusion Biochemical phenotypes consistent with sPA may represent an early cardiometabolic state associated with elevated risk of MACE, even before overt PA criteria are met. The absence of standardized diagnostic thresholds and randomized interventional data currently limits clinical translation. Prospective trials evaluating renin-guided screening and early mineralocorticoid receptor antagonism are needed to determine whether intervention at the subclinical stage reduces long-term cardiovascular harm.

Abstract Background Inflammatory bowel disease (IBD) can lead to a hypercoagulable state, particularly at initial diagnosis. Consequently, venous thromboembolism (VTE) represents a serious complication associated with IBD. For children, the risk of VTE near the time of IBD diagnosis has not yet been quantified, and guidance for VTE prophylaxis remains unclear. Methods This multisite matched case-control study examined pediatric patients with a new diagnosis of IBD from 2019-2024. Cases were those who developed VTE ≤30 days prior or ≤90 days post IBD diagnosis. Controls were newly diagnosed IBD patients without VTE. Each case was matched to 2-6 controls based on IBD subtype and age at IBD diagnosis. Demographics, laboratory values, prothrombotic risk factors and treatments were compared between matched cases and controls using conditional logistic regression stratified, by case sets. Results Study subjects included 15 cases and 52 controls, resulting in 70 matched pairs. Factors associated with early VTE included lower hemoglobin (P = .003), lower albumin (P = .002), corticosteroids use (P = .01), central line (P = .002), and any surgery ≤90 days post IBD diagnosis (P = .001). No association with VTE was detected for platelets, C-reactive protein, fecal calprotectin, family history of IBD or body mass index. Conclusions Albumin, hemoglobin, steroid use, central line, and any surgery ≤90 days post IBD diagnosis were associated with early VTE. These risk factors may be used in a future prediction model to stratify newly diagnosed pediatric IBD patients by their risk for early VTE development.

ABSTRACT Pregnancy-associated acute kidney injury (PrAKI) remains a major contributor to maternal and foetal morbidity worldwide, with an estimated incidence of 40–100 per 10 000 pregnancies. PrAKI is substantially more prevalent in low- and middle-income countries. Unlike acute kidney injury episodes unrelated to pregnancy, PrAKI arises in a unique physiological context characterized by haemodynamic adaptation, immune tolerance, hormonal modulation, and the presence of the foetal–placental unit. These pregnancy-specific factors alter renal reserve, endothelial stability, and inflammatory responsiveness. The pathogenesis of PrAKI is multifactorial. Haemodynamic vasodilation and increased glomerular filtration rates during pregnancy reduce renal functional reserve, rendering the kidney vulnerable to hypovolemia and sepsis. Placental ischaemia drives the release of antiangiogenic factors, particularly soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, causing systemic endothelial dysfunction and glomerular endotheliosis. Disruption of immune tolerance and complement regulation further contributes to microangiopathy and autoimmune-mediated renal injury. Structural urinary tract changes, metabolic stressors, and maternal comorbidities amplify susceptibility. Beyond the index event, PrAKI has lasting consequences. Maladaptive renal repair promotes chronic kidney disease and long-term cardiovascular risk, while foetal exposure to uremic toxins and placental dysfunction contribute to intrauterine growth restriction, prematurity, and reduced nephron mass with lifelong cardio-renal implications. Understanding the pathophysiology of PrAKI, particularly endothelial, immunologic, and placental interactions, has direct diagnostic and therapeutic implications, including the use of angiogenic biomarkers and targeted haemodynamic strategies. Future research must prioritize molecular predictors, global registries, and mechanistic studies to reduce intergenerational kidney and cardiovascular disease.

Abstract Patients with atypical variants of Alzheimer's disease (AD) often present at a younger age with predominantly non‐amnestic impairments and a more aggressive disease course. Historically, individuals with atypical presentations have not been included in large‐scale clinical trials, which typically focus on late‐onset, sporadic amnestic‐predominant AD. Consequently, treatment options and research efforts specific to atypical AD remain limited. The emergence of amyloid‐targeting therapies that slow disease progression underscores these challenges, as evidence supporting their efficacy in early‐onset amnestic and non‐amnestic AD variants is scarce. This perspective article argues that atypical AD represents an excellent disease model for clinical trials and proposes strategies to address critical gaps in clinical trial design for this population. Key considerations include optimizing participant selection approaches, establishing syndrome‐specific or surrogate biological and clinical endpoints, and fostering advocacy to enhance early and accurate diagnosis, equitable representation, and outcomes for these populations.