Citations

BACKGROUND: Randomized trials comparing radial and femoral access report access site crossover rates of 3% to 9% for radial access and 1% to 3% for femoral access. However, contemporary real-world crossover rates are not well characterized. The aim was to evaluate contemporary trends and predictors of vascular access site crossover during percutaneous coronary intervention (PCI). METHODS: We analyzed index PCI procedures recorded in the National Cardiovascular Data Registry CathPCI Registry from 2018 to 2024. Access site crossover was identified using documented access data, with radial-to-femoral crossover inferred when the final successful access site was femoral. Temporal trends and clinical predictors of crossover were examined. Operator experience was assessed using cumulative total and radial PCI volumes from 2011 to 2024 as captured in CathPCI Registry versions 4 and 5. RESULTS: Among 3 861 790 index PCIs, 192 902 (5.0%) involved access site crossover, with a modest increase over time. Radial-to-femoral crossover accounted for 81.2% of crossover events. Factors independently associated with crossover included older age, female sex, higher body mass index, and peripheral vascular disease. Operators with the lowest total PCI volume and the lowest radial PCI volume experienced the highest crossover rates. Notably, operators with low radial PCI volume demonstrated a substantial decline in radial-to-femoral crossover over the study period. CONCLUSIONS: In contemporary clinical practice, access site crossover rates are consistent with those reported in randomized trials. Although crossover occurs more frequently among lower-volume operators, rates decline with increasing operator experience, supporting the presence of a radial access learning curve and improvement in procedural performance over time.

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

Myelodysplastic syndromes with isolated deletion of chromosome 5q [MDS-del(5q)] constitute a distinct biological entity traditionally associated with favorable outcomes, although up to one quarter of patients progress to acute myeloid leukemia (AML). Existing prognostic models, developed in heterogeneous MDS populations, may not adequately capture risk within this subgroup. We assembled an international cohort of 682 patients with MDS-del(5q) to evaluate the performance of the IPSS-R and IPSS-M, identify prognostic variables, and develop a disease-specific prognostic tool, the IPSS-del(5q). Most patients were classified as lower-risk by IPSS-R (94.4%) and IPSS-M (85.5%), yet both systems showed limited discriminatory ability (C-indices ≈0.5). Independent adverse prognostic factors included age ≥70 years, male sex, anemia (hemoglobin ≤10 g/dL), thrombocytopenia (platelets ≤100×10⁹/L), the presence of one additional chromosomal abnormality, ≥2 gene mutations, SF3B1 mutations, and high-risk TP53 status. Six variables were included in the IPSS-del(5q), stratifying patients into standard-risk (74.3%) and high-risk (25.7%) groups with significantly different LFS (69.2 vs. 32.0 months; p<0.01). Moreover, this model reclassified 19.1% of lower-risk IPSS-R and 14.6% of lower-risk IPSS-M patients into the high-risk IPSS-del(5q) group. However, its discriminative power remained modest, with a C-index of 0.60. Overall, this study provides the most comprehensive prognostic evaluation of MDS-del(5q) to date, demonstrates the limited discriminatory capacity of existing MDS scores in this entity, and underscores the need to develop refined disease-specific prognostic approaches for this MDS subtype.

Large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4) predominantly affects children and young adults (CAYA) and presents as localized disease with excellent prognosis. Although most tumors harbor IRF4 rearrangements (IRF4-R), the existence of cryptic rearrangements has been suggested. Whether IRF4-R LBCL in adults represents the same biological entity remains unclear. To address this question, 35 CAYA patients diagnosed with LBCL-IRF4 and 7 adult (>40-year-old) LBCL with IRF4-R were investigated by an integrative molecular approach. Targeted sequencing structural variant analysis (SV-NGS) confirmed the IRF4-R in 84% of investigated cases. In CAYA, an enrichment (55% vs 29% in adults) of translocations involving IGH, with a breakpoint cluster 3' to IRF4 (EXOC2) was observed, including a cryptic insertion of IGHM-IGHJ5 into IRF4 locus. Novel translocations, IRF4::MIR142 in two CAYA (7%) and IRF4::BATF in one adult, were discovered. Whole-exome sequencing analysis identified unreported mutations in LBCL-IRF4 as YY1 and ZC3H12A (11% each). The high incidence of mutations affecting the B-cell receptor/NF-KB pathways in LBCL-IRF4 was confirmed in cases with diffuse component only. None of the CAYA tumors were classified by LymphGen tool. Adult IRF4-R LBCL showed higher levels of genetic complexity and a distinct mutational profile with mutations on KMT2D and DTX1 (43% each), and MYD88-L265P (29%), and were predicted as EZB or MCD (29% each). These differential genetic features were in line with different clinical presentations (extranodal involvement and advanced stage). In conclusion, IRF4-R architecture and mutational profile differ according to age, supporting that not all cases should be classified as LBCL-IRF4.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Background: Increased posterior tibial slope (PTS) and anterior tibial translation (ATT) result in a higher risk of anterior cruciate ligament reconstruction failure. Accurate measurement of PTS and ATT is essential to guide surgical planning in these patients. Full-length weightbearing lateral tibial radiographs yield the most accurate measurement of PTS and ATT compared with short-film tibial radiographs, computed tomography scans, and magnetic resonance imaging. Indications: We aim to demonstrate a validated, reproducible technique in a stepwise fashion to accurately measure PTS and ATT using full-length weightbearing lateral tibial radiographs. This presentation adds to the field by offering a precise measurement technique for surgical planning purposes. Technique Description: To precisely measure PTS using a full-length weightbearing lateral tibial radiograph, first, perpendicular lines are drawn 5 cm proximal to the ankle joint and 5 cm distal to the knee joint. A line is then extended proximally from the center of the perpendicular line near the ankle through the center of the perpendicular line near the knee, and then extended up to the tibial articular surface. Next, a line is drawn along the medial tibial plateau. The angle measured between these 2 lines is subtracted from 90° to yield the PTS. To precisely measure ATT, a line is drawn along the diaphysis of the tibia and approximated to the posterior aspect of the proximal tibia. Then, another parallel line is drawn and approximated to the posterior aspect of the distal femur. The distance between these lines is measured to yield anterior tibial translation. Results: We measured a PTS of 14.2° and an ATT of 12.6 mm using the technique described in this presentation. Discussion/Conclusion: This technique demonstrates an accurate and reproducible method to precisely measure PTS and ATT using full-length weightbearing lateral tibial radiographs. This technique yields greater accuracy in PTS and ATT than other imaging modalities. As a result, there is a direct benefit for surgical planning when using this technique. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Abstract Background Quality assurance (QA) in radiation therapy is a critical component of ensuring accurate and consistent patient treatments, but many tasks are time consuming and rely on human visual acuity, which limits their accuracy. Purpose We aimed to automate monthly mechanical QA tests, improve measurement accuracy and precision, and decrease inter‐user variability using a computer vision‐based quality assurance (CVQA) system. Methods A custom marker board incorporating four ArUco markers was created along with a custom camera holder that mounted onto the gantry head. OpenCV was utilized to automate tests for couch translation, collimator and table angles, collimator and table walkout, optical distance indicator (ODI), and field size detection. A GUI was created to guide users through the tests, determine passing status of measurements based on MPPG8.b criteria, and display image captures to allow users to troubleshoot if needed. Reproducibility tests were taken across four days. The system was tested against manual measurements by graph paper or digital level for each test. Field sizes and ODI were read by 12 different physicists to determine human variability and comparisons for CVQA. Results The CVQA system took 5 min to set up and 7 min to perform all tests. All field sizes, collimator/table angles, collimator/table walkout, and table translations were reproducible within 0.5 mm and 0.5°. ODI measurements were reproducible within 1 mm. Table travel, ODI, and walkout measurements agreed with manual measurements within 0.5 mm and 0.4°, except for vertical table motions that agreed within 0.9 mm due to the lens focus being optimized for the 100 cm SSD plane. The standard deviation between physicists for almost all symmetric and asymmetric jaws was larger than the reproducibility of CVQA. CVQA has been utilized for five years and has demonstrated ability to identify mechanical machine issues. Conclusions CVQA successfully automates mechanical QA tasks, providing an efficient and precise system. CVQA is open source and freely available for academic institutions. Its adoption can improve workflow efficiency and consistency in clinical environments.

Cancer therapy has dramatically changed over the past many decades, not only in efficacy but also complexity, with targeted therapeutics that have novel mechanisms of action. As a direct result of these remarkable treatments that have extended the lives of many patients, the increased recognition of cancer therapy-related cardiac dysfunction as well as the broader description of cancer therapy-related cardiovascular toxicity (CTR-CVT) has become obvious. The discipline of cardio-oncology has accepted the challenge to provide excellent cardiovascular (CV) protection for our patients being treated for cancer in order to achieve the best overall outcomes. The successful application of optimal CV protection by cardio-oncology needs to incorporate basic principles to realise these improved overall outcomes. Critical paradigm principles include: (1) using effective CV therapy; (2) targeting the likely mechanisms of action responsible for CTR-CVT; and (3) documenting cancers and cancer therapies associated with high CTR-CVT. Such a CV protection paradigm is likely to have the biggest impact and confirm an improved overall outcome. In addition, it is important to emphasise that knowing those cancers with high CTR-CVT risk requires careful comparative study of CV endpoints during exploratory cancer trials. Furthermore, astute clinical observations of specific CTR-CVT should be routinely reported to allow the development of strategies that minimise the negative impact of CTR-CVT. Lastly, coordinated efforts that allow realistic goals of cancer treatment while minimising the impact of CTR-CVT are the end goal in order to eliminate CV disease as a barrier to effective cancer treatment.

ABSTRACT Background Implementation of remote robotic‐assisted surgery (rRAS) has the potential to significantly improve access to high‐quality surgical care for patients worldwide. Advances in robotic systems and telecommunications now enable highly reliable, low latency, and cybersecure connectivity. These technological developments, together with the broader adoption of telemedicine, have driven an increasing interest in the implementation of rRAS. Methods The Clinical Robotic Surgery Association (CRSA) convened a conference to develop international clinical recommendations for rRAS using the Danish Model of Consensus. The society identified five key issue categories and invited a panel of experts to address specific questions for each. Panel members and a jury of 10 unbiased, non‐expert in rRAS professionals participated in a day‐long conference on November 19, 2025 (Los Angeles, USA). During the conference, participants presented, discussed, and reached consensus on specific guidelines relevant to each category. Immediately after the conference, the jury reviewed and approved the recommended guidelines. Results Multiple recommendations were approved for each of the following categories: Operating Models, Roles and Responsibilities (2 recommendations), Clinical Pathway (2 recommendations), Emergency Management (8 recommendations), Technical Considerations (5 recommendations), and Medico‐legal and Ethical Considerations (4 recommendations). Conclusions There was consensus that with recent advances in telecommunication and robotic technologies, rRAS can be offered safely and effectively if the identified safeguards are realized. Adoption of rRAS is expected to continue advancing rapidly.