Citations

Importance Clinical trials in cardiovascular medicine aim to deliver high-quality evidence with greater efficiency, including smaller sample sizes and shorter timelines. The selection of sensitive and reliable end points is central to this goal. Right ventricular (RV) structure and function play a critical role in many cardiovascular conditions; however, RV-specific parameters remain underused and inconsistently applied in interventional clinical trials. In this article, the current and emerging role of RV-focused imaging and hemodynamic parameters as end points in clinical trials are explored and a comprehensive framework for their development, validation, and broader implementation is proposed. Observations Across multiple disease domains, RV-focused parameters derived from echocardiography, cardiac magnetic resonance imaging, computed tomography, and right-sided heart catheterization demonstrate potential value in assessing the therapeutic effects of new medicines or devices across a wide range of conditions including heart failure, cardiomyopathies, valve diseases, pulmonary hypertension, and congenital heart conditions. However, their use is inconsistent, and feasibility challenges are common, particularly in multicenter clinical trial settings. Key limitations include variability in imaging acquisition, incomplete data capture, lack of standardized protocols, and insufficient validation linking short-term RV changes to long-term clinical outcomes. Emerging tools such as artificial intelligence may improve reproducibility and efficiency, while collaborative, multidisciplinary efforts are essential for advancing end-point development. Conclusions and Relevance RV-specific end points hold substantial promise for enhancing the sensitivity and mechanistic insight of clinical trials but remain inadequately integrated into current practice. Optimal end-point selection requires balancing clinical relevance, analytical validity, and operational feasibility, with consideration of disease-specific pathophysiology and trial design. Standardization of acquisition, validation of clinically meaningful changes, and centralized data analysis are important next steps. Broader adoption of robust RV metrics supported by technological innovation and cross-sector collaboration has the potential to improve trial efficiency, accelerate therapeutic development, and ultimately enhance patient outcomes.

Abstract Background: Digital Drug Assignment (DDA) is a computational reasoning model that scores cancer therapies based on the complete molecular profile of a tumor, and stratifies them by predicted efficacy (Petak et al., 2021). In a prior study of 111 lung cancer patients, DDA-derived high-score molecularly targeted agents (MTAs) were associated with improved clinical outcomes (Dirner et al., 2025). Here, we extend this analysis to the GENIE BPC NSCLC cohort to assess the broader clinical validity of DDA. Methods: From the GENIE BPC NSCLC cohort data available on Synapse, we included 1,078 patients with a single-sample genomic profile, available primary treatment data and survival outcomes (total 2,103 treatment lines, therapies included: afatinib, erlotinib, osimertinib, crizotinib, nivolumab, pembrolizumab, atezolizumab, bevacizumab+chemo, ramucirumab+chemo; and chemotherapy alone). DDA scores were generated for all cases, and the individual score of the administered MTAs (incl. immune checkpoint inhibitors) was used to stratify outcomes into low (<0), intermediate, and high DDA-score (≥1000) tiers. Progression-free survival (PFS, by imaging) and overall survival (OS) were analyzed using Kaplan-Meier statistics. Results: Median PFS and OS differed significantly across DDA score tiers, increasing with higher scores (see table). Intermediate-tier drugs had similar mPFS values as chemotherapies (3.9 vs 4.2 months). Six-month PFS and twelve-month OS rates increased with DDA-tiers and were all significantly different by χ2 test. DDA-high therapies provided greater benefit across treatment types than lower-score counterparts. Conclusions: Across a large, real-world NSCLC cohort, DDA effectively distinguished therapies with higher clinical efficacy based on the full molecular profile of each patient. These results reinforce the potential of DDA to enhance personalized treatment selection based on NGS diagnostics in precision oncology. Citation Format: Barbara Vodicska, Eniko Kispeter, Dora Lakatos, Gabor Gy Kalmar, Robert Doczi, Dora Gorog-Tihanyi, Anna Dirner, Reka Szalkai-Denes, William T. Beck, Arkadiusz Z. Dudek, Christophe Le Tourneau, Istvan Petak. Molecularly-informed prediction of treatment efficacy in the GENIE BPC NSCLC cohort using computational reasoning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7.

Abstract Background and Aims Intestinal ultrasound (IUS) is increasingly used to monitor treatment efficacy in inflammatory bowel disease (IBD) trials. However, standardized definitions for response, remission, and optimal assessment timing remain undefined. An international expert consensus meeting was held to establish IUS endpoints for clinical trials. Methods A panel of 35 international gastroenterologists and radiologists participated in a modified Delphi process, reviewing the literature and developing consensus statements. Agreement was defined as at least 75% consensus. Results Consensus was reached on 150 statements across four domains: general IBD (30 statements), luminal Crohn’s disease (CD) (43), perianal CD (51), and ulcerative colitis (UC) (26). For luminal CD and UC, ultrasound response was defined by: (1) a ≥25% reduction in bowel wall thickness (BWT) from baseline, or (2) multifactorial improvement, combining BWT reduction with ≥1 grade decrease in color Doppler signal (CDS) or another IUS parameter. Assessments were set at weeks 4-8 for the colon and week 12 for the terminal ileum. Ultrasound remission in luminal CD was defined as: (1) BWT normalization (≤3 mm) or (2) normalization of multiple parameters, including BWT, CDS, and all other IUS parameters. Similar remission criteria were proposed for UC, but the sigmoid BWT normal range (3-4 mm) remained uncertain. The bowel ultrasound score (BUSS) for CD and the Milan ultrasound criteria (MUC) for UC were supported as standardized scoring systems for trials. Conclusion This consensus provides standardized IUS definitions to enhance consistency in IBD trials, supporting the integration of IUS in future research.

Abstract During the 20th century, inflammatory bowel disease (IBD) was considered a disease of early-industrialized regions in North America, Europe, and Oceania. At the turn of the 21st century, incidence of IBD increased in newly-industrialized and emerging regions in Africa, Asia, and Latin America, while prevalence in early-industrialized regions started to grow steadily. Changes in incidence and prevalence denote evolution of IBD across four epidemiologic stages: Stage 1 (Emergence), characterized by low incidence and prevalence; stage 2 (Acceleration in Incidence), characterized by rapidly rising incidence and low prevalence; and stage 3 (Compounding Prevalence), characterized by decelerating, plateauing, or declining incidence and steadily rising prevalence. A fourth stage (Prevalence Equilibrium) has been proposed where the slope of prevalence plateaus due to shifting demographics of an aging IBD population, but it has not yet been evidenced. To date, these stages have been theoretical without specific incidence/prevalence indicators defining transition points. Using real-world data from 490 population-based studies comprising 80 global regions and spanning over a century (1920–2023), we show spatiotemporal transitions across stages 1–3 and model transition towards stage 4. Understanding the evolution of IBD across epidemiologic stages allows healthcare systems to better prepare for the future worldwide burden of IBD.

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel diseases (IBD), affect approximately seven million people globally. The continuous rise in IBD prevalence and the aging of populations will inevitably lead to an increasing use of health care resources. In parallel with these trends, continuing innovations in IBD therapeutics, diagnostics, and preventatives are creating more options for IBD patients seeking to reduce their disease burden. These trends pose an imminent burden on health care systems and require that we identify modifiable cost drivers in IBD care and develop strategies for delivering equitable and affordable care for all patients. Methods This Lancet Gastroenterology & Hepatology Commission, consisting of a diverse faculty of health care professionals with expertise in the field of IBD and health economists, was formed to deliver an extensive summary of the literature and discuss key topics on the costs and cost-effectiveness of treating IBD in the present, and how this is likely to look in the future. Furthermore, it offers suggestions for how to deliver affordable IBD care in the coming years. The report’s focus was on high-income countries in Europe, North America, Australia and New Zealand, and Asia. Results The Commission drew together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, as well as how to deliver affordable care for IBD in the future. The key conclusions are that (i) increases in health care costs must be evaluated against improved disease control and reductions in indirect costs, and (ii) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and cost-effectiveness of care. International collaborations should be sought in order to evaluate novel models of care (such as value-based health care, including integrated health care and participatory health care models), as well as to improve the education and training of clinicians, patients, and policymakers. Measures to reduce the costs of IBD care are summarised in Table 1. Conclusion Increases in health care costs must be evaluated against improved disease control and reductions in indirect costs. Evaluations should be systematically aligned between countries and regions. Detailed analysis of the current epidemiology and the likely effects of changing IBD management on disease course and socioeconomic outcomes is essential; and will become even more imperative in the era of precision medicine, where complex biotechnologies will require expensive analyses, highly skilled personnel, and drug development for what may sometimes be relatively small patient groups.

INTRODUCTION: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS: The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS: The overall median hospitalization rate was 42.4 with an interquartile range of 29.7–60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = −3.9%; 95% CI: −4.4, −3.3) and morality rates (AAPC = −4.7%; 95% CI: −5.6, −3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021. DISCUSSION: PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.

Abstract Introduction Cardiopulmonary exercise testing (CPET) is an important diagnostic method to evaluate athletes and non-athletes, however we do not have widely accepted normal values for correct evaluation and interpretation in the young. Goals Our aim was to compare CPET parameters of young athletes and non-athletes and determine reference values. Methods Exercise tests were performed in young non-athletes, aged <18 years between 2011 to 2016 at Mayo Clinic. Athletes underwent detailed sports cardiology screening including CPET at Semmelweis University Heart and Vascular Center between 2016 and 2018. Individuals with cardiovascular disease were excluded. We created 2 subgroups in both sexes: 12–14 years (Group 1), 15–17 years (Group 2). Statistical analysis was performed using SAS with analysis of variance under the general linear model adjusting for age, body mass index and test effort based on peak respiratory exchange ratio (RER). Results A total of 212 athletes (92% male, 15.5±0.6ys) and 207 non-athletes (68% male, 15.0±0.7ys) were included in the analysis. In Group 1 boys, athletes have higher peak HR (200.0±9.2 vs 188.5±16.8 bpm, p<0.0001), HR reserve (117.1±14.5 vs 108.9±19.8 bpm p<0.05), VO2 max (53.7±6.6 vs 44.7±9.1 mL/kg/min p<0.0001), ventilation (VE) (120.3±25.0 vs 70.7±21.6 L/min p<0.0001) and RER (1.12±0.0 vs 1.07±0.08, p <.001) compared to controls. In Group 2 boys, there was no difference in peak HR and HR reserve, but athletes have higher VO2 max (57.2±4.7 vs 45.3±9.3 mL/kg/min, p<0.0001) and VE (150.7±23.7 vs 104.1±25.9 L/min, p<0.0001), similarly as Group 2 girls: VO2 max (46.3±3.6 vs 34.9±8.5 mL/kg/min p<0.0001), VE (118.7±12.5 vs 68.4±20.6 L/min, p<0.0001). In male athletes, peak HR (200.6±9.2 vs 196.5±7.4 bpm p<0.05) and HR recovery (34.2±9.8 vs 29.8±11.1 bpm p<0.05) decreases with age, while VO2 max (53.7±6.6 vs 57.2±4.7 mL/kg/min, p<0.001) and VE (120.3±24.9 vs 150.7±23.7 L/min, p<0.0001) increases. Lower cut-off values were determined in each group (Figure). Lower-cut off values Conclusion We created a unique Mayo-Semmelweis database of young athletes and non-athletes. As a result of intensive training, athletes show higher levels of CPET variables vs non-athletes. Our study provides CPET reference values in the pediatric age group, applying them could contribute to correct evaluation and interpretation of CPET, increasing its diagnostic potential.

The initial description of Carney complex (CNC) in 1985 included myxomas, spotty skin pigmentation, and endocrine overactivity (of the adrenal, the pituitary, and the testis). In 1997, thyroid neoplasms were found in 3 patients with CNC and involvement of the gland in the syndrome was apparent. Herein, we describe the clinical, pathologic, and follow-up findings in 26 patients with CNC and a disorder of the thyroid gland. The patients were predominantly middle-aged women with an asymptomatic thyroid mass. Four patients had hyperthyroidism, which was caused by follicular hyperplasia in 2 patients and by toxic adenoma in 2 others. Pathologic findings included benign lesions (follicular hyperplasia, nodular hyperplasia, and follicular adenoma) in 16 patients and carcinomas (follicular or papillary) in 10 patients. The follicular carcinomas had unusual features, multifocality, bilaterality, and lymph node metastasis. The tumor was fatal in 3 of 4 patients with a tumor ≥3 cm in diameter. One patient had an unusual multifocal microscopic follicular hyperplasia. Detection and treatment of the thyroid neoplasms in patients with CNC requires long-term follow-up of patients with the syndrome.