University Health Network

Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) lower LDL cholesterol and may influence cancer through immunomodulatory pathways. However, their effect on human cancer incidence remains unknown. We conducted a retrospective, propensity score-matched study (Clalit Health Services, Israel, 2010-2023) comparing PCSK9 mAbs to ezetimibe. Adults prescribed PCSK9 mAbs for 6 months or more were matched 1:3 to ezetimibe-treated patients without prior cancer, applying a 1-year latency. The cohort included 9,876 patients (2,469 PCSK9 mAb; 7,407 ezetimibe; mean age 65). During a median 4.6-year follow-up, cancer occurred in 12% of PCSK9 mAb users and 11% of ezetimibe users (HR 1.09 [95% CI, 0.95-1.25]). In sex-stratified analysis, men on PCSK9 mAbs had a higher cancer incidence (12.5% vs. 10.3%, P = 0.03); no difference was observed in women. All-cause mortality was significantly lower in the PCSK9 mAb group (3% vs. 5%; HR 0.65 [95% CI, 0.54-0.80]). Post-cancer-diagnosis mortality did not differ. In this large cohort, PCSK9 mAb therapy appeared safe regarding overall cancer risk and was associated with a significant reduction in all-cause mortality; the slightly higher cancer incidence in men may likely be attributed to a higher prevalence of baseline risk factors.

Nanoparticles have become an essential platform for next-generation drug delivery and therapeutic development, yet clinical translation remains limited by an incomplete understanding of their interactions within human biological systems. Organ-on-a-chip technology offers a powerful approach to evaluate efficacy and safety of nanomedicine under physiologically relevant conditions in human cells by recreating fluid flow, mechanical stress, barrier function, immune interactions and inter-organ communications. These advanced in vitro systems allow quantitative assessments of nanoparticle transport, distribution, and safety with improved human relevance compared to conventional cell culture and animal models. The integration of sensors within organ-on-a-chip platforms enables real-time monitoring of tissue responses and nanoparticle kinetics. Advances in automation and robotic liquid handling support scalable and reproducible testing across multiple tissue models. Artificial intelligence and active learning tools facilitate automated data analysis and experimental optimization, paving the way towards self-driving nanomedicine evaluation platforms that accelerate discovery and clinical translation.

To provide recommendations for the most appropriate endovascular intervention of femoropopliteal (FP) arterial disease based on plaque characterization. A panel of 22 physicians from multiple disciplines participated in a modified Delphi consensus, leveraging the RAND/UCLA Appropriateness Method. Panelists engaged in 2 rounds of voting, following a literature review, with an in-person discussion prior to the second round of voting. A rigorous statistical approach was used to analyze the points of agreement and disagreement. Consensus-based recommendations on the most appropriate endovascular approaches for treating patients with FP lesions, stratified by lesion morphology, were generated. Overall, 490 individual items were included in the voting, 458 (93%) of which achieved consensus and 32 (7%) were nonconsensus items, based on a priori criteria under the following categories: (a) recommendations on method for determining plaque morphology, (b) preferred endovascular devices for vessel preparation and definitive treatment stratified by (i) plaque morphology and (ii) Tosaka classification of in-stent restenosis, and (c) vessel preparation device safety-related considerations. This international, multidisciplinary consensus provides evidence- and expert-informed recommendations for vessel preparation and definitive treatment of FP arterial disease, tailored to plaque morphology. These consensus recommendations aim to support clinical decision making and promote best interventional practices by serving as an expert opinion supplement to existing guideline-based care pathways.