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Immunotherapy has changed the treatment paradigm for many types of cancer, but immune checkpoint inhibitors (ICIs) have not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to the immunosuppressive prostate tumor microenvironment (TME) and is associated with poor response to ICIs. The primary source of inflammatory cytokine production is the inflammasome. Here, we identify PIM kinases as important regulators of inflammasome activation in tumor associated macrophages (TAMs). Analysis of clinical data from a cohort of treatment naïve, hormone responsive PCa patients revealed that tumors from patients with high PIM1/2/3 display an immunosuppressive TME characterized by high inflammation (IL-1β and TNFα) and a high density of repressive immune cells, most notably TAMs. Strikingly, macrophage-specific knockout of PIM reduced tumor growth in syngeneic models of prostate cancer. Transcriptional analyses indicate that eliminating PIM from macrophages enhanced the adaptive immune response and increased cytotoxic immune cells. Combined treatment with PIM inhibitors and ICIs synergistically reduced tumor growth. Immune profiling revealed that PIM inhibitors sensitized PCa tumors to ICIs by increasing tumor suppressive TAMs and increasing the activation of cytotoxic T cells. Collectively, our data implicate macrophage PIM as a driver of inflammation that limits the potency of ICIs and provides preclinical evidence that PIM inhibitors are an effective strategy to improve the efficacy of immunotherapy in prostate cancer.

Introduction: Laparoscopy has demonstrated improved outcomes in abdominal surgery; however, its use in trauma has been less compelling. In this study, we hypothesize that laparoscopy may be observed to have lower costs and complications with similar operative times compared to open exploration in appropriately selected patients., Methods: We retrospectively reviewed adult patients undergoing abdominal exploration after blunt and penetrating trauma at our level 1 center from 2008 to 2020. Data included mechanism, operative time, length of stay (LOS), hospital charges, and complications. Patients were grouped as follows: therapeutic and nontherapeutic diagnostic laparoscopy and celiotomy. Therapeutic procedures included suture repair of hollow viscus organs or diaphragm, evacuation of hematoma, and hemorrhage control of solid organ or mesenteric injury. Unstable patients, repair of major vascular injuries or resection of an organ or bowel were excluded., Results: Two hundred ninety-six patients were included with comparable demographics. Diagnostic laparoscopy had shorter operative times, LOS, and lower hospital charges compared to diagnostic celiotomy controls. Similarly, therapeutic laparoscopy had shorter LOS and lower hospital costs compared to therapeutic celiotomy. The operative time was not statistically different in this comparison. Patients in the celiotomy groups had more postoperative complications. The differences in operative time, LOS and hospital charges were not statistically significant in the diagnostic laparoscopy compared to diagnostic laparoscopy converted to diagnostic celiotomy group, nor in the therapeutic laparoscopy compared to the diagnostic laparoscopy converted to therapeutic laparoscopy group., Conclusions: Laparoscopy can be used safely in penetrating and blunt abdominal trauma. In this cohort, laparoscopy was observed to have shorter operative times and LOS with lower hospital charges and fewer complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)

While most friction burns are adequately managed in an outpatient setting, many may require hospital admission, operative excision, and extended care. To this day, there is a wide variance in friction burn management. Our goal is to review the etiology, management, and outcomes of such burns warranting hospitalization. We conducted a retrospective review of all friction burns admitted to a single, American Burn Association-verified burn center from January 1, 2016 to December 31, 2020. A total of 28 (34%) patients required surgery for their friction burns and 15 (18%) ultimately required a split-thickness skin graft. The mean number of operations was 2.4 (95% CI 1.6-3.1). Overall, the operative group was younger (29.9 vs 38.3 years, P = .026), more likely to have a concomitant traumatic brain injury (25% vs 7%, P = .027), and had a longer hospital length of stay (17.5 vs 3.9 days, P < .001). Both groups had a similar overall TBSA (8.5% vs 10.0%, P = .35), but the operative group had a larger surface area comprised of third-degree burns (3.05% vs 0.2%, P < .001). Overall, friction burns resulting in hospital admission are associated with high-energy traumatic mechanisms and concomitant injuries. Patients who need operative intervention for their burns typically require multiple procedures often culminating in a split-thickness skin graft. While non-operative management of friction burns with topical agents has been found to be successful, patients with higher injury severity scores should be monitored very closely as they may require surgical excision., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Most diseases that affect human beings across the world are now treated with drugs of organic origin. However, some of these are associated with side effects, toxicity, and resistance phenomena. For the treatment of many illnesses, the development of new molecules with pharmacological potential is now an urgent matter. The biological activities of metal complexes have been reported to have antitumor, antimicrobial, anti-inflammatory, anti-infective and antiparasitic effects, amongst others. Metal complexes are effective because they possess unique properties. For example, the complex entity possesses the effective biological activity, then the formation of coordination bonds between the metal ions and ligands is controlled, metal ions provide it with extraordinary mechanisms of action because of characteristics such as d-orbitals, oxidation states, and specific orientations; metal complexes also exhibit good stability and good physicochemical properties such as water solubility. Platinum is a transition metal widely used in the design of drugs with antineoplastic activities; however, platinum is associated with side effects which have made it necessary to search for, and design, novel complexes based on other metals. Copper is a biometal which is found in living systems; it is now used in the design of metal complexes with biological activities that have demonstrated antitumoral, antimicrobial and anti-inflammatory effects, amongst others. In this review, we consider the open horizons of Cu(II)- and Pt(II)-based complexes, new trends in their design, their synthesis, their biological activities and their targets of action.

Lipid droplets (LDs) are dynamic organelles with a neutral lipid core surrounded by a phospholipid monolayer. Solid tumors exhibit LD accumulation, and it is believed that LDs promote cell survival by providing an energy source during energy deprivation. However, the precise mechanisms controlling LD accumulation and utilization in prostate cancer are not well known. Here, we show peroxisome proliferator-activated receptor α (PPARα) acts downstream of PIM1 kinase to accelerate LD accumulation and promote cell proliferation in prostate cancer. Mechanistically, PIM1 inactivates glycogen synthase kinase 3 beta (GSK3β) via serine 9 phosphorylation. GSK3β inhibition stabilizes PPARα and enhances the transcription of genes linked to peroxisomal biogenesis (PEX3 and PEX5) and LD growth (Tip47). The effects of PIM1 on LD accumulation are abrogated with GW6471, a specific inhibitor for PPARα. Notably, LD accumulation downstream of PIM1 provides a significant survival advantage for prostate cancer cells during nutrient stress, such as glucose depletion. Inhibiting PIM reduces LD accumulation in vivo alongside slow tumor growth and proliferation. Furthermore, TKO mice, lacking PIM isoforms, exhibit suppression in circulating triglycerides. Overall, our findings establish PIM1 as an important regulator of LD accumulation through GSK3β-PPARα signaling axis to promote cell proliferation and survival during nutrient stress., (© 2023. The Author(s).)