RESUMO
INTRODUCTION: Perioperative bleeding increases morbidity and mortality in sarcoma patients. Tranexamic acid (TXA), an antifibrinolytic, is widely utilized in non-sarcoma orthopaedic surgeries, but its adoption in sarcoma surgery is hindered by concerns about thrombotic events. METHODS: Searches in Ovid MEDLINE, EMBASE, and CENTRAL were performed without date restrictions. Inclusion criteria encompassed sarcoma patients undergoing surgery with TXA intervention. Two authors independently screened studies, resolved conflicts, and assessed biases. RESULTS: Eight studies met inclusion criteria, comprising 2142 patients. TXA administration varied in dose and timing across studies. Meta-analysis revealed significantly reduced mean blood loss with TXA of -462.5 mL ([95% confidence interval [CI: -596.7, -328.31], p < 0.001) but no difference in transfusion rates (odds ratio [OR] = 0.51 [95% CI: 0.14-1.89]) or venous thromboembolism events (OR = 0.93 [95% CI: 0.40, 2.16]). Study biases were predominantly moderate to high due to retrospective designs and lack of control for confounders. Quality of reporting varied, with limitations identified in outcome reporting and effect size estimation. CONCLUSIONS: Despite evidence of reduced blood loss, the absence of prospective studies limits conclusive recommendations on TXA use in sarcoma surgery. Further research is warranted to determine optimal TXA regimens and assess safety concerns regarding thrombotic events in this patient population.
RESUMO
Programmed cell death protein 1 (PD-1), a receptor on T cells, and its ligand, PD-L1, have been a topic of much interest in cancer research. Both tumour and virus-infected cells can upregulate PD-L1 to suppress cytotoxic T-cell killing. Research on the PD-1/PD-L1 axis has led to the development of anti-PD-1/PD-L1 immune checkpoint blockades (ICBs) as promising cancer therapies. Although effective in some cancer patients, for many, this form of treatment is ineffective due to a lack of immunogenicity in the tumour microenvironment (TME). Despite the development of therapies targeting the PD-1/PD-L1 axis, the mechanisms and pathways through which these proteins are regulated are not completely understood. In this review, we discuss the latest research on molecules of inflammation and innate immunity that regulate PD-L1 expression, how its expression is regulated during viral infection, and how it is modulated by different cancer therapies. We also highlight existing research on the development of different combination therapies with anti-PD-1/PD-L1 antibodies. This information can be used to develop better cancer immunotherapies that take into consideration the pathways involved in the PD-1/PD-L1 axis, so these molecules do not reduce their efficacy, which is currently seen with some cancer therapies. This review will also assist in understanding how the TME changes during treatment, which will provide further rationale for combination therapies.