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Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate of just 13 %. Conventional therapies fail due to acquired chemoresistance. We previously identified MutY-Homolog (MYH), a protein that repairs oxidative DNA damage, as a therapeutic target that induces apoptosis in PDAC cells. However, we did not understand the mechanism driving these anti-PDAC effects, nor did we have a means to therapeutically inhibit MYH. In this study, we demonstrated that MYH inhibition induces DNA damage and checkpoint activation in PDAC cells. Using a clinically-relevant PDAC mouse model, we showed that therapeutic MYH-siRNA delivery using Star 3 nanoparticles increased intratumoural PDAC cell death, but did not inhibit tumour growth. Finally, we showed that MYH knockdown in PDAC cells sensitised them to the anti-proliferative and anti-clonogenic effects of oxaliplatin and olaparib. Our findings identify a potential novel therapeutic approach for PDAC that induces a therapeutically exploitable DNA repair vulnerability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Locally advanced or recurrent prostate cancer which invades adjacent pelvic organs, bone or other soft tissue structures is a rare situation. This study aimed to report the outcomes of ten consecutive patients who underwent total pelvic exenteration for prostate cancer at a high-volume specialist centre. Two patients had locally advanced primary tumours, while eight had locally recurrent prostate cancer. Median operating time, blood loss, ICU stay, and hospital stay was 12.2 h (range 9.6-13.8), 2500 ml (500-3000), 4.5 days (2-7) and 36 days (21-78), respectively. There was no inpatient, 30-day, or 90-day mortality. Six patients developed a Clavien-Dindo III complication. R0 resection was achieved in eight patients. Median follow up was 16 months (range 2-77). At last follow up, five patients were alive without disease. These findings suggest that pelvic exenteration for locally advanced and recurrent prostate cancer is safe and represents a potentially curative treatment option for highly selected patients., Competing Interests: Declaration of competing interest All the authors have made a significant contribution to this manuscript, have seen and approved the final manuscript, and have agreed to its submission to the EJSO. There are no conflicts of interest to declare., (© 2024 Published by Elsevier Ltd.)

Atherosclerosis is complex chronic disease characterized by intimal cholesterol accumulation and vascular inflammation. There is a well-established relationship of hypercholesterolemia and inflammation with atherosclerosis. However, the link between inflammation and cholesterol is not completely understood. Myeloid cells, in particular, monocytes, macrophages, and neutrophils play essential roles in the pathogenesis of atherosclerotic cardiovascular disease. It is well known that macrophages accumulate cholesterol, forming foam cells, which drive atherosclerosis-associated inflammation. However, the interaction between cholesterol and neutrophils remains poorly defined-an important gap in the literature given that neutrophils represent up to 70% of total circulating leukocytes in humans. Elevated levels of biomarkers of neutrophil activation (myeloperoxidase and neutrophil extracellular traps) and higher absolute neutrophil counts are both associated with increased rates of cardiovascular events. Neutrophils contain the necessary machinery to uptake, synthesize, efflux and esterify cholesterol; yet, the functional consequence of dysregulated cholesterol homeostasis on neutrophil activity remains poorly defined. Preclinical animal data suggest a direct link between cholesterol metabolism and hematopoiesis, although current evidence in humans has been unable to corroborate such findings. This review will explore the impact of impaired cholesterol homeostasis neutrophils and draw focus on the discordant data from animal models and atherosclerotic disease in humans.

Background: Early results have illustrated the multiportal robotic approach to be safe and oncologically efficacious in the treatment of thoracic malignancies. Industry leaders have improved upon the lessons learned during the early multiportal studies and have now come to establish the feasibility of the biportal, and subsequently the uniportal robotic-assisted approach, all in an effort to offer patients equivalent or better outcomes with less surgical trauma. No current, coherent body of evidence currently exists outlining the early-term outcomes of patients undergoing uniportal robotic-assisted thoracic surgery. This systematic review and meta-analysis sought to clarify the early-phase outcomes of these patients., Methods: An electronic search of four databases was performed to identify relevant studies outlining the immediate post-operative outcomes of patients undergoing uniportal robotic-assisted thoracic surgeries. The primary endpoint was defined as technical success (i.e., no conversion to secondary robotic, video-assisted thoracoscopic, or open approaches). Secondary endpoints of interest included post-operative outcomes and complication rates. A meta-analysis using a random effects model of proportions or means was applied, as appropriate., Results: The search strategy ultimately yielded 12 relevant studies for inclusion. A total of 240 patients (52% male) split across cohort studies and case reports were identified. The mean age of the two groups was 59.7±3.0 and 58.1±6.8 years, respectively. The mean operative time was 133.8±38.2 and 150.0±52.2 minutes, respectively. Length of hospital stay was 4.4±1.6 and 4.3±1.1 days, respectively. The mean blood loss was 80.0±25.1 mL The majority of identified procedures were lobectomies, segmentectomies, and wedge resections, though complex sleeve resections and anterior mediastinal mass resections were also completed. Cumulative technical success was 99.9%., Conclusions: The uniportal robotic-assisted approach, when completed in expert hands, has been illustrated to have exceedingly low rates of conversion to secondary procedures, along with short length of stay (LOS), minimal blood loss, and short procedural times (variable depending on operation type). Current evidence on the feasibility of this approach will be bolstered by upcoming multi-institutional series., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2023 Annals of Cardiothoracic Surgery. All rights reserved.)