The Virtual Vision of Neurosurgery: How Augmented Reality and Virtual Reality are Transforming the Neurosurgical Operating Room.

BACKGROUND: In this era of imagination and technological innovation, mixed reality systems such as virtual reality (VR) and augmented reality (AR) are contributing to a wide array of neurosurgical care, from the betterment of surgical planning and surgical comfort to even novel treatments and improved resident education. These systems can augment procedures that require high-level dexterity such as minimally invasive surgery, tumor excisions, as well as peripheral and neurovascular surgery. Herein, the authors will define and compare the technological features, indications, and characterized outcomes of VR and AR systems in the context of neurosurgery through a review of the literature to date. Moreover, this review will discuss the limitations of VR and AR while including an overview of the cost effectiveness of each of these systems. METHODS: An extensive review of published literature on augmented reality and virtual reality was performed utilizing PubMed, OVID Medline, and EMBASE journals from January 1, 2006 to April 2, 2022. Terms used for the search included augmented reality, spinal surgery, virtual reality, and neurosurgery. RESULTS: The search yielded full text English language-related articles regarding virtual and augmented reality application, limitations, and functional outcomes in neurosurgery. An initial set of 121 studies were screened and reviewed for content. There were 13 studies included that involved 162 patients, 550 screw placements, 58 phantom spines, and learning points from simulation training of 276 involved residents. CONCLUSION: This literature review examines recent research into virtual and augmented reality applications in neurosurgical care. The literature establishes there are technological features, indications, outcomes, limitations, and cost effectiveness differences between these systems. Based on ongoing and evolving applications of the VR and AR systems, their innovative potential they make available to the future of neurosurgical patient care makes clear the need for further studies to understand the nuances between their differing technological advances

XBP1-KLF9 Axis Acts as a Molecular Rheostat to Control the Transition from Adaptive to Cytotoxic Unfolded Protein Response

Summary: Transcription factor XBP1s, activated by endoplasmic reticulum (ER) stress in a dose-dependent manner, plays a central role in adaptive unfolded protein response (UPR) via direct activation of multiple genes controlling protein refolding. Here, we report that elevation of ER stress above a critical threshold causes accumulation of XBP1s protein sufficient for binding to the promoter and activation of a gene encoding a transcription factor KLF9. In comparison to other XBP1s targets, KLF9 promoter contains an evolutionary conserved lower-affinity binding site that requires higher amounts of XBP1s for activation. In turn, KLF9 induces expression of two regulators of ER calcium storage, TMEM38B and ITPR1, facilitating additional calcium release from ER, exacerbation of ER stress, and cell death. Accordingly, Klf9 deficiency attenuates tunicamycin-induced ER stress in mouse liver. These data reveal a role for XBP1s in cytotoxic UPR and provide insights into mechanisms of life-or-death decisions in cells under ER stress. : The transcription factor XBP1s plays a central role in suppression of endoplasmic reticulum (ER) stress through direct activation of multiple genes controlling protein refolding. Fink et al. report that elevation of ER stress above a certain threshold triggers an XBP1s-dependent transcriptional program, leading to exacerbation of ER stress and cell death. Keywords: endoplasmic reticulum stress, XBP1s, KLF9, TMEM38B, ITPR1, calcium channel, UP

A Purine Nucleotide Biosynthesis Enzyme Guanosine Monophosphate Reductase Is a Suppressor of Melanoma Invasion

Melanoma is one of the most aggressive types of human cancers, and the mechanisms underlying melanoma invasive phenotype are not completely understood. Here, we report that expression of guanosine monophosphate reductase (GMPR), an enzyme involved in de novo biosynthesis of purine nucleotides, was downregulated in the invasive stages of human melanoma. Loss- and gain-of-function experiments revealed that GMPR downregulates the amounts of several GTP-bound (active) Rho-GTPases and suppresses the ability of melanoma cells to form invadopodia, degrade extracellular matrix, invade in vitro, and grow as tumor xenografts in vivo. Mechanistically, we demonstrated that GMPR partially depletes intracellular GTP pools. Pharmacological inhibition of de novo GTP biosynthesis suppressed whereas addition of exogenous guanosine increased invasion of melanoma cells as well as cells from other cancer types. Our data identify GMPR as a melanoma invasion suppressor and establish a link between guanosine metabolism and Rho-GTPase-dependent melanoma cell invasion

Oral rivaroxaban for the treatment of symptomatic pulmonary embolism.

BACKGROUND: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism. METHODS: In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. RESULTS: Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups. CONCLUSIONS: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.)