Ultrasound-guided nerve blocks in emergency medicine practice: 2022 updates.

OBJECTIVES: In the Emergency Department (ED), ultrasound-guided nerve blocks (UGNBs) have become a cornerstone of multimodal pain regimens. We investigated current national practices of UGNBs across academic medical center EDs, and how these trends have changed over time. METHODS: We conducted a cross-sectional electronic survey of academic EDs with ultrasound fellowships across the United States. Twenty-item questionnaires exploring UGNB practice patterns, training, and complications were distributed between November 2021-June 2022. Data was manually curated, and descriptive statistics were performed. The survey results were then compared to results from Amini et al. 2016 UGNB survey to identify trends. RESULTS: The response rate was 80.5% (87 of 108 programs). One hundred percent of responding programs perform UGNB at their institutions, with 29% (95% confidence interval (CI), 20%-39%) performing at least 5 blocks monthly. Forearm UGNB are most commonly performed (96% of programs (95% CI, 93%-100%)). Pain control for fractures is the most common indication (84%; 95% CI, 76%-91%). Eighty-five percent (95% CI, 77%-92%) of programs report at least 80% of UGNB performed are effective. Eighty-five percent (95% CI, 66%-85%) of programs have had no reported complications from UGNB performed by emergency providers at their institution. The remaining 15% (95% CI, 8%-23%) report an average of 1 complication annually. CONCLUSIONS: All programs participating in our study report performing UGNB in their ED, which is a 16% increase over the last 5 years. UGNB's are currently performed safely and effectively in the ED, however practice improvements can still be made. Creating multi-disciplinary committees at local and national levels can standardize guidelines and practice policies to optimize patient safety and outcomes.

PPRX-1701, a nanoparticle formulation of 6'-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models.

Derivatives of the Chinese traditional medicine indirubin have shown potential for the treatment of cancer through a range of mechanisms. This study investigates the impact of 6'-bromoindirubin-3'-acetoxime (BiA) on immunosuppressive mechanisms in glioblastoma (GBM) and evaluates the efficacy of a BiA nanoparticle formulation, PPRX-1701, in immunocompetent mouse GBM models. Transcriptomic studies reveal that BiA downregulates immune-related genes, including indoleamine 2,3-dioxygenase 1 (IDO1), a critical enzyme in the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) immunosuppressive pathway in tumor cells. BiA blocks interferon-γ (IFNγ)-induced IDO1 protein expression in vitro and enhances T cell-mediated tumor cell killing in GBM stem-like cell co-culture models. PPRX-1701 reaches intracranial murine GBM and significantly improves survival in immunocompetent GBM models in vivo. Our results indicate that BiA improves survival in murine GBM models via effects on important immunotherapeutic targets in GBM and that it can be delivered efficiently via PPRX-1701, a nanoparticle injectable formulation of BiA.

Cytomegalovirus infection of glioblastoma cells leads to NF-κB dependent upregulation of the c-MET oncogenic tyrosine kinase.

Cytomegalovirus (CMV) is widespread in humans and has been implicated in glioblastoma (GBM) and other tumors. However, the role of CMV in GBM remains poorly understood and the mechanisms involved are not well-defined. The goal of this study was to identify candidate pathways relevant to GBM that may be modulated by CMV. Analysis of RNAseq data after CMV infection of patient-derived GBM cells showed significant upregulation of GBM-associated transcripts including the MET oncogene, which is known to play a role in a subset of GBM patients. These findings were validated in vitro in both mouse and human GBM cells. Using immunostaining and RT-PCR in vivo, we confirmed c-MET upregulation in a mouse model of CMV-driven GBM progression and in human GBM. siRNA knockdown showed that MET upregulation was dependent on CMV-induced upregulation of NF-κB signaling. Finally, proneural GBM xenografts overexpressing c-MET grew much faster in vivo than controls, suggesting a mechanism by which CMV infection of tumor cells could induce a more aggressive mesenchymal phenotype. These studies implicate the CMV-induced upregulation of c-MET as a potential mechanism involved in the effects of CMV on GBM growth.