Signal transducer and activator of transcription 3 (STAT3) is a potent regulator of gliomagenesis through its induction of angiogenesis, host immunosuppression, and tumor invasion. Gain of function mutations result in constitutive activation of STAT3 in glioma cells, making STAT3 an attractive target for inhibition in cancer therapy. Nevertheless, some studies show that STAT3 also participates in terminal differentiation and apoptosis of various cell lines and in glioma with phosphatase and tensin homolog (PTEN)-deficient genetic backgrounds. In light of these findings, the utility of STAT3 as a prognostic indicator and as a target of drug therapies will be contingent on a more nuanced understanding of its pro- and anti-tumorigenic effects.

The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.

BACKGROUND AND OBJECTIVES: Nosocomial infections are the most common complication among critically ill patients and contribute to poor long-term outcomes. Patients with aneurysmal subarachnoid hemorrhage (aSAH) are highly susceptible to perioperative infections, yet it is unclear what factors influence infection onset and functional recovery. The objective was to investigate risk factors for perioperative infections after aSAH and relate causative pathogens to patient outcomes. METHODS: Clinical records were obtained for 194 adult patients with aSAH treated at our institution from 2016 to 2020. Demographics, clinical course, complications, microbiological reports, and outcomes were collected. χ², univariate, and multivariate logistic regression analyses were used to analyze risk factors. RESULTS: Nearly half of the patients developed nosocomial infections, most frequently pneumonia and urinary tract infection. Patients with infections had longer hospital stays, higher rates of delayed cerebral ischemia, and worse functional recovery up to 6 months after initial hemorrhage. Independent risk factors for pneumonia included male sex, comatose status at admission, mechanical ventilatory use, and longer admission, while those for urinary tract infection included older age and longer admission. Staphylococcus, Klebsiella, and Enterococcus spp. were associated with poor long-term outcome. Certain pathogenic organisms were associated with delayed cerebral ischemia. CONCLUSION: Perioperative infections are highly prevalent among patients with aSAH and are related to adverse outcomes. The risk profiles for nosocomial infections are distinct to each infection type and causative organism. Although strong infection control measures should be universally applied, patient management must be individualized in the context of specific infections.