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Objectives: Rates of locoregional recurrence and distant metastases are high following curative-intent resection for patients with localized pancreatic adenocarcinoma. Adjuvant therapies have been investigated with the intent to reduce the risk of recurrence and improve OS. The objective of this study is to update and summarize the current evidence for adjuvant therapy following surgical resection for nonmetastatic PDAC with a focus on high-level evidence and randomized controlled trials is provided. Methods: This multispecialty-led committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and surgical oncology. Using the population, intervention, comparator, outcome, timing and study design framework, evidence regarding treatment outcomes was assessed using Cochrane and PRISMA methodology. Eligible studies included prospective and retrospective (n≥25) studies published between January 1, 2013 and February 13, 2026, from Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Review, and Scopus databases. Study type and quality were assessed. Well-established RAND/UCLA consensus methodology (modified Delphi) was used to rate the appropriateness of the treatment options. Results: Of the 74 references used as evidence, 74 are categorized as therapeutic references. Study type and quality for the references were assessed, and included 31 well-designed studies (phase II randomized and phase III), 14 moderately well-designed studies that account for most common biases (matched cohort and phase II studies), 28 studies with design limitations (retrospective reviews), and 1 reference meta-analysis. Conclusions: This systematic review and guidelines provide up-to-date recommendations focusing on recent advancements for adjuvant treatment of resected PDAC using modern systemic therapy regimens and selective use of radiotherapy using modern techniques.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

ABSTRACT Objective(s) Fetal pleural effusion is a rare condition that may significantly impact fetal and neonatal outcomes. Currently, no universal standardized approach exists for diagnosing and managing primary fetal pleural effusions. This study aimed to develop structured, expert‐based clinical guidelines for the diagnosis, monitoring, management, and follow‐up care of primary fetal pleural effusion. Methods A Delphi method was employed to achieve consensus among an international panel of experts in fetal medicine. Experts were selected based on their clinical expertise, affiliations, and relevant publications. A three‐round anonymous electronic survey was sent to the full panel. In the initial two rounds, participants rated each statement on a Likert scale (1–5) and provided suggestions for modifications. Statements with a median score of five and no suggested changes were accepted as consensus. Statements with a median score below four were rejected. Statements scoring a median of four were revised according to suggestions and reconsidered in the subsequent round. In the final round, participants indicated their agreement or disagreement with the remaining statements. Consensus was defined as agreement from more than 70% of participants with no suggestions for further changes. Results A total of 101 expert clinicians accepted the invitation and completed the first round with 73 (72%) completing all three rounds. Consensus statements were achieved on aspects of diagnosis, monitoring, intervention, post‐intervention management, and delivery. Key recommendations concerning the diagnosis of primary fetal pleural effusion include the use of ultrasound as the primary modality for identifying fetal pleural effusion and excluding secondary causes through detailed genetic, infectious, and metabolic evaluations. Management strategies emphasized thoracoamniotic shunting as the preferred intervention in hydropic fetuses with primary pleural effusion. Experts reached consensus that shunt placement could be offered as early as 16 weeks. No consensus was reached for isolated effusion without hydrops, as management was considered case‐dependent. The importance of ultrasonographic monitoring of fetal status at least weekly post‐intervention was strongly endorsed. Conclusion(s) The Delphi method facilitated the development of a consensus‐based protocol for diagnosing and managing primary fetal pleural effusion. These standardized guidelines are intended to enhance clinical practice across various settings, improve perinatal outcomes, and serve as a foundation for future research for this high‐risk fetal condition.

Objectives: To summarize the current evidence for radiation therapy (RT) in the prevention and treatment of heterotopic ossification (HO), including patient selection, optimal RT technique, and associated risks. Methods: This multispecialty-led committee includes radiation oncologists, rheumatologists, orthopedic surgeons, and physical medicine/rehabilitation physicians. Using the population, intervention, comparator, outcome, timing and study design (PICOTS) framework, evidence regarding treatment outcomes was assessed using Cochrane and PRISMA methodology. Eligible studies included prospective and retrospective studies published between January 1, 1980, and November 1, 2025, from Embase, Medline, and PubMed databases. Of the 197 articles identified using the search strategy, 83 were selected for inclusion as evidence, including 27 well-designed studies (phase II randomized and phase III), 16 moderately well-designed studies that account for most common biases (matched cohort and phase II studies), 31 studies with design limitations (retrospective reviews), 2 supplemental studies (not useful as primary evidence), and 7 meta-analyses. Additional studies were included to provide context and were not used to guide recommendations. Well-established RAND-UCLA consensus methodology (modified Delphi) was used to rate the appropriateness of the treatment options. Results: The results of this analysis demonstrate that in appropriately selected patients, RT is an effective and safe therapy for prophylaxis of HO formation. Conclusions: This systematic review provides consensus guidelines for the use of RT as prophylaxis of HO based on current peer-reviewed evidence in the literature.

Objective Data on cardiac index (CI) in patients undergoing coronary angiography (CAG) can enhance decision-making and improve clinical outcomes. However, this necessitates an additional invasive procedure, and therefore, it is frequently omitted. This study explores the novel application of convolutional neural networks (CNNs) to predict CI from routine CAGs. Methods and analysis Patients who underwent CAG and simultaneous right heart catheterisation at Mayo Clinic between 2002 and 2023 were included. A three-dimensional (3D)-CNN model (X3D architecture) was developed to predict binary CI categories (normal: CI≥2.2 vs abnormal: CI<2.2 L/min/m²) from CAG videos. CAGs were randomly split into training (70%), validation (15%) and test (15%) sets. All available videos from each study were entered into the model. The model’s performance was evaluated using the area under the curve (AUC), sensitivity, specificity and F1 score. Results A total of 15 297 CAG studies were considered. After applying a quality-check algorithm to exclude low-quality or irrelevant CAGs, 11 475 studies from 9103 patients were included. CI was abnormal in 25.2% of studies. The model achieved an AUC of 0.83 (95% CI 0.81 to 0.85), sensitivity of 0.72 (95% CI 0.68 to 0.77), specificity of 0.78 (95% CI 0.75 to 0.80) and F1 score of 0.62 (95% CI 0.58 to 0.65) on the test dataset. Limiting the input to 4, 3 or 2 prespecified CAG videos representing standard views did not significantly affect the model’s performance, supporting its applicability in varied clinical workflows. Conclusions This study demonstrates the feasibility of leveraging deep learning models to predict CI from CAG videos. The proposed 3D-CNN model shows promise as a tool for providing physicians with real-time data to aid decision-making during CAG procedures.

Abstract Myelodysplastic syndromes (MDS) are clinically and biologically diverse disorders, emphasizing the need for personalized treatment approaches. The International Working Group for Prognostication of MDS (IWG_PM) recently introduced a molecular classification, referred to as the MDS taxonomy, that categorizes patients into 16 subgroups based on 21 gene mutations, 6 cytogenetic abnormalities, and loss of heterozygosity (LOH) at TP53 and TET2 loci. This study sought to validate and enhance the clinical relevance of the MDS taxonomy by analyzing a large retrospective cohort ( n = 5136) and transcriptomic data from a prospective cohort ( n = 477). The taxonomy successfully identified subgroups with distinct clinical characteristics and disease progression patterns. However, incorporating gene interactions from taxonomy subgroups did not improve the prognostic performance of the Molecular International Prognostic Scoring System (IPSS‐M). We further assessed whether the taxonomy could guide management in patients receiving disease‐modifying therapies. Except for the “ TP53 ‐complex” subgroup, taxonomy classifications were not predictive of hypomethylating agent response or transplant outcomes. Nonetheless, they correlated with overall survival, suggesting that while both IPSS‐M and the taxonomy capture disease biology, other non‐genetic factors may influence treatment response. RNA sequencing confirmed the biological distinctiveness of the taxonomy groups. Transcriptomic profiling of CD34+ bone marrow cells revealed unique, homogeneous gene expression patterns, particularly within the AML‐like, bi TET2 , SF3B1 , and TP53 ‐complex subgroups. Further integration of multi‐omics data may refine MDS classification, improving clinical decision‐making and guiding the development of targeted therapies.

Abstract This literature‐based systematic review and associated guidelines provide evidence‐based paradigms for the management of locoregionally recurrent rectal cancer (LRRC). This multispecialty committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and colorectal surgery. As is the standard, the previously described American Radium Society Appropriate Use Criteria methodology for this project was followed rigorously, with the Population, Intervention, Comparator, Outcome, Timing, and Study Design framework and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses methodology to assess the evidence. RAND/University of California Los Angeles consensus methodology (modified Delphi) was used to rate the appropriateness of treatment options. Published between January 1, 2013, and July 16, 2025, 116 peer‐reviewed trials provided the evidence: 10 were well‐designed randomized phase 2/3 trials, 29 were moderately well designed trials that accounted for most common biases (matched cohort and phase 2), 76 trials had design limitations (retrospective), and one was a meta‐analysis. Clinical cases were created as examples to illustrate current acceptable management of LRRC. Treatment and prognosis are influenced by prior therapy and the site(s) and extent of LRRC. The ability to achieve a margin‐negative surgical resection is the ultimate determinant of survival and local control. Preoperative systemic therapy, radiation therapy, or a combination of the two can facilitate tumor downsizing and improve the likelihood of a margin‐negative resection. An individualized multidisciplinary approach is required to ensure the best outcome. Although this review does not suggest a major alteration of current practice, it provides reassuring evidence of the importance of combined‐modality therapy.

BACKGROUND: The EARLY TAVR trial (Evaluation of TAVR Compared to Surveillance for Patients with Asymptomatic Severe Aortic Stenosis) demonstrated that early transcatheter aortic valve replacement (TAVR) was superior to clinical surveillance (CS) in asymptomatic severe aortic stenosis. The relative impact of early TAVR versus CS strategy by age is unknown. METHODS: The study population of the EARLY TAVR trial was stratified into 4 age groups: 65 to 69 years (n=141), 70 to 74 years (n=263), 75 to 79 years (n=250), and ≥80 years (n=247). Associations between age and the trial primary end point of death, stroke, or unplanned cardiovascular hospitalization; the composite end point of death, stroke, or heart failure hospitalization; and its individual components were examined. Interaction tests evaluated whether the treatment effect of early TAVR versus CS differed by age. RESULTS: No interaction was detected between age and the treatment effect of early TAVR versus CS for the composites or individual outcomes. We observed lower stroke rates with early TAVR compared with CS in the youngest (65–69 years, absolute risk reduction, 13%; P =0.008) and oldest (≥80 years; absolute risk reduction, 12.3%; P =0.029) age groups. The absolute difference in heart failure hospitalization rates between the early TAVR and CS arms at 2 years was greatest in the oldest patients (≥80 years, 9.1%; 75–79 years, 5.9%; 70–74 years, 5.1%; 65–69 years, 4.4%). In the CS group, time to conversion to AVR was similar across all age groups (median, 11 months; P =0.73). Approximately one-third of younger patients (65–69 years) in the CS arm presented with acute valve syndrome at the time of conversion, the frequency of which tended to increase with age ( P =0.06). CONCLUSIONS: In the EARLY TAVR trial, the relative benefit of early TAVR over CS was consistent among all age groups. The greatest absolute reduction in stroke rate with early TAVR compared with CS appeared in the youngest and oldest groups, whereas reduction in heart failure hospitalization was most pronounced in the oldest patients. These data suggest that early TAVR should be considered in all age groups above 65 years. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03042104.

e19094 Background: WM/LPL is an indolent B-cell Non-Hodgkin Lymphoma with prolonged survival and predisposition to secondary malignancies (SM) influencing clinical outcomes and survivorship care. We evaluated the incidence, demography, treatment utilization, and outcomes of SM in patients with WM/LPL using population-based data. Methods: SEER-22 database was used to identify patients with LPL/WM diagnosed between 2000–2022 and stratified by SM. Overall survival (OS) was analyzed using Kaplan–Meier survival analysis and propensity score matched Cox regression was used to assess mortality risk. Hazard ratios were reported, with p<0.05 deemed significant. Results: 22,170 patients with WM/LPL were identified, with a median age of 71 years (IQR 16); the cohort was predominantly male (59.0%), White (84.0%), had a median household income of $50,000–$75,000 (48.9%), and resided primarily in urban areas (89.5%). Among all WM/LPL patients, 20.8% (n=4,615) developed a SM. Patients who developed SM were older than those without (median age 75 vs 70 years, p<0.0001) with 45.2% alive at predefined follow-up. The most common solid organ SM were gastrointestinal adenocarcinoma (16%), prostate cancer (14%), and lung adenocarcinoma (9%), while the leading hematologic SM were plasma cell myeloma (6%), diffuse large B-cell lymphoma (5%), and myelodysplastic syndrome (2%). 35.3% of the cohort received chemotherapy, while 0.1% received cancer-related surgery or radiation. On multivariable analysis, older age (OR 0.82, 95% CI 0.81–0.83), male sex (OR 0.59, 95% CI 0.44–0.80), urban residence (OR 1.99, 95% CI 1.24–3.18), and higher income (OR 2.16, 95% CI 1.13–4.15) were significantly associated with SM diagnosis. Kaplan–Meier analysis demonstrated inferior survival among patients with SM (54.8% vs 45.2%, p<0.0001), with shorter median OS (9 vs 14 years, log-rank p<0.001). Similarly, Propensity-matched analysis revealed worse OS in patients with SM (HR 1.15, 95% CI 1.09–1.22, p<0.001). Median OS varied substantially by SM site (see Table). Conclusions: Our study demonstrates a substantial burden of SMs among patients with WM/LPL and are associated with substantially inferior survival despite the indolent nature of the disease. The marked heterogeneity in SM types and outcomes highlights the need for risk-adapted surveillance, survivorship-focused care, and equitable strategies to address disparities and improve long-term outcomes in this population. SM Site Median OS (years) IQR p-value Hepatopancreatobiliary 1 0 <0.05 CNS 3.5 9 <0.05 Breast 3 6 <0.05 Colorectal 4 3.5 <0.05 Lymph Node 5 8 <0.05 Blood 6 7 <0.05 Lung 7 9 <0.05 Head & Neck 6.5 8.5 <0.05 Melanoma 9 10 <0.05 Urogenital 10.5 7 <0.05

e14111 Background: Primary CNSL (PCNSL) is a rare, aggressive B-cell non-Hodgkin lymphoma limited to the CNS, while secondary CNSL (SCNSL) represents CNS involvement from systemic lymphoma. Previous observations focused on CNSL have limited data clinically comparing PSNSL and SCNSL. We aimed to evaluate overall survival and associated factors in patients with PCNSL vs SCNSL using a large population database. Methods: We conducted a retrospective cohort study using the SEER-22 database to identify patients diagnosed with CNSL between 2020-2022. Group comparisons used t-tests or ANOVA for continuous variables, chi-square tests for categorical variables, and Kaplan–Meier survival analysis, with all analyses performed in RStudio 4.1.1 and significance deemed as p<0.05. Results: 14,964 patients with CNS lymphoma were identified, with 84.6% PCNSL and 15.4% SCNSL cases. The overall median age was 65 years (IQR 20), with 52% male, 66% White patients, residing in urban areas (90%) and median household income of $50,000–$75,000 (52%). Compared with PCNSL, patients with SCNSL were significantly older (72 vs 64 years, p<0.0001). SCNSL more frequently involved the cerebrum (39% vs 34%) and cerebellum (5.5% vs 4.5%), but less commonly affected the nerves (12.0% vs 12.5%) and spinal cord (4.2% vs 5.1%) (p<0.05). Disease was predominantly unilateral (95.8%) in both groups. Chemotherapy (55% vs 56%) and radiotherapy (19% vs 18%) utilization did not differ significantly, with external beam radiation comprising 94.3% of radiated cases. PCNSL patients were more likely to undergo surgical intervention than SCNSL patients (31.8% vs 28.7%; p=0.0027). Diffuse large B-cell lymphoma was the most common histologic subtype in both PCNSL (70.1%) and SCNSL (74.3%). Median overall survival was shorter in SCNSL (1.64 years) than PCNSL (1.99 years). Survival improved significantly across diagnostic eras (2000–2005 to 2016–2020; log-rank p<0.001), while lower income (<$50,000) and rural residence were associated with inferior outcomes (p=0.028 and p=0.033). Conclusions: Survival in CNS lymphoma remains poor, with SCNSL associated with worse outcomes compared with PCNSL. Greater understanding of treatment variation and disease differences is needed to optimize therapy and improve patient outcomes. Characteristic PCNSL SCNSL Total p-Value N 12667 2297 14964 Population Distribution 0.033 Urban 11426 2038 13464 Rural 1241 259 1500 Surgery 0.0027 Yes 3630 730 4360 No 9037 1567 10604 Months from Diagnosis to Rx(Mean, SD) 0.31 (0.86) 0.27 (0.65) 0.30 (0.83) 0.0077 Death Status <0.0001 Dead 8603 1772 10375 Alive 4064 525 4589 Overall Survival (in years, Mean, SD) 1.99 (2.85) 1.64 (2.31) 1.93 (2.77) <0.0001