Does Extended Reality Simulation Improve Surgical/Procedural Learning and Patient Outcomes When Compared With Standard Training Methods?: A Systematic Review.

INTRODUCTION: The use of extended reality (XR) technologies, including virtual, augmented, and mixed reality, has increased within surgical and procedural training programs. Few studies have assessed experiential learning- and patient-based outcomes using XR compared with standard training methods. METHODS: As a working group for the Society for Simulation in Healthcare, we used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a PICO strategy to perform a systematic review of 4238 articles to assess the effectiveness of XR technologies compared with standard training methods. Outcomes were grouped into knowledge, time-to-completion, technical proficiency, reactions, and patient outcomes. Because of study heterogeneity, a meta-analysis was not feasible. RESULTS: Thirty-two studies met eligibility criteria: 18 randomized controlled trials, 7 comparative studies, and 7 systematic reviews. Outcomes of most studies included Kirkpatrick levels of evidence I-III (reactions, knowledge, and behavior), while few reported level IV outcomes (patient). The overall risk of bias was low. With few exceptions, included studies showed XR technology to be more effective than standard training methods in improving objective skills and performance, shortening procedure time, and receiving more positive learner ratings. However, XR use did not show significant differences in gained knowledge. CONCLUSIONS: Surgical or procedural XR training may improve technical skill development among trainees and is generally favored over standard training methods. However, there should be an additional focus on how skill development translates to clinically relevant outcomes. We recommend longitudinal studies to examine retention and transfer of training to clinical settings, methods to improve timely, adaptive feedback for deliberate practice, and cost analyses.

Impact of metabolic syndrome on morbidity and mortality following transforaminal interbody fusion (TLIF).

Study design: Retrospective Multi-Institutional Database Study. Objective: Investigate the effect of metabolic syndrome (MetS) on the outcomes of Transforaminal Lumbar Interbody Fusion (TLIF). Summary of background data: TLIF procedures in lumbar spine pathology are common. MetS is a combination of conditions, including medication required hypertension, diabetes mellitus (DM), and body mass index (BMI) of 30 kg/m2s or more. The prevalence of MetS has increased drastically over the past two decades. Our study aimed to understand the effect of MetS on morbidity and mortality of TLIF postoperatively. Methods: Our study used American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) data from 2006 to 2019 to find all patients who underwent TLIF. Patients with MetS were compared to those without MetS. Fisher's test identified univariate relationships between MetS and preoperative/postoperative variables. Multivariable logistic regression models were utilized to analyze the association between MetS and postoperative morbidity and mortality. Results: 54,980 patients were identified who received TLIF. 10.7 % had MetS preoperatively. Patients with and without MetS showed statistically significant univariate differences in most preoperative and postoperative variables. After adjusting for preoperative comorbidities, patients with MetS had greater multivariate-adjusted odds of wound infections (aOR = 1.5889, CI 1.1952-2.112, p = 0.00144), pulmonary events (aOR = 1.5517, CI 1.1207-2.1485, p = 0.00813), renal events (aOR = 2.8685, CI 1.5511-5.3045, p = 0.00078), sepsis (aOR = 1.6773, CI 1.1647-2.4155, p = 5.44E-03), and return to OR (aOR = 1.4764, CI 1.2201-1.7866, p = 6.19E-05). Conclusions: Patients with MetS are at elevated risk for various morbidity and mortality markers after TLIF. Surgeons performing TLIFs on these patients should be aware of the increased potential for postoperative events that may complicate the patient's recovery. Level of evidence: Level III.

Impact of Obesity on Anterior Cervical Discectomy and Fusion (ACDF): Postoperative Morbidity and Mortality.

AIM: To investigate the impact of obesity on postoperative morbidity and mortality in patients who underwent anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS: The American College of Surgeons' National Surgical Quality Improvement Project (NSQIP) files from 2006 to 2019 were queried for all patients who underwent an ACDF. Fisher exact tests were used in analyzing univariate differences in preoperative comorbidities and postoperative morbidity and mortality between patients with and without obesity (BMI ?30 kg/ m < sup > 2 < /sup > ). Results with a p value < 0.05 were considered statistically significant. Multivariable logistic regression models were used in determining the independent impact of obesity on ACDF postoperative morbidity and mortality. A p value < 0.017 was required for multivariate statistical significance. RESULTS: There were 96,882 patients who underwent an ACDF from 2006 to 2019 found. 53.77% had non-obese BMI. Patients had statistically significant differences in most perioperative comorbidities and postoperative outcomes on univariate analysis. On multivariate analysis, patients with obesity has decreased adjusted odds of wound infections (aOR=0.7208, CI 0.574-0.9075, p=0.0053), pulmonary events (aOR=0.7939, CI 0.6903-0.9129, p=0.0012), sepsis (aOR=0.5670, CI 0.4359-0.7374, p=2.32E-05), transfusion requirements (aOR=0.5396, CI 0.4498-0.6473, p=3.04E-11), return to operating room (aOR=0.7537, CI 0.6727-0.8447, p=1.17E-06), and length of stay > 10 days (aOR=0.7061, CI 0.6438-0.7744, p=1.49E-13). CONCLUSION: Obesity is a protective factor toward ACDF postoperative complications. Obesity as a marker of patient selection criteria for ACDF procedures should not be used by spine surgeons.

Deciphering the water quality impacts of COVID-19 human mobility shifts in estuaries surrounding New York City.

The COVID-19 pandemic altered human mobility, particularly in large metropolitan areas. In New York City (NYC), stay-at-home orders and social distancing led to significant decreases in commuting, tourism, and a surge of outward migration. Such changes could result in decreased anthropogenic pressure on local environments. Several studies have linked COVID-19 shutdowns with improvements in water quality. However, the bulk of these studies primarily focused on short-term impacts during shutdown periods, without assessing longer-term impacts as restrictions eased. Here, we examine both concurrent lockdown and societal reopening impacts on water quality, using pre-pandemic baseline conditions, in two highly urbanized estuaries surrounding NYC, the New-York Harbor estuary and Long Island Sound (LIS). We compiled datasets from 2017 to 2021 of mass-transit ridership, work-from-home trends, and municipal wastewater effluent to assess changes in human mobility and anthropogenic pressure during multiple waves of the pandemic in 2020 and 2021. These were linked to changes in water quality assessed using high spatiotemporal ocean color remote sensing, which provides near-daily observations across the estuary study regions. To distinguish anthropogenic impacts from natural environmental variability, we examined meteorological/hydrological conditions, primarily precipitation and wind. Our results show that nitrogen loading into the New York Harbor declined significantly in the spring of 2020 and remained below pre-pandemic values through 2021. In contrast, nitrogen loading into LIS remained closer to the pre-pandemic average. In response, water clarity in New-York Harbor significantly improved, with less of a change in LIS. We further show that changes in nitrogen loading had higher impact on water quality than meteorological conditions. Our study demonstrates the value of remote sensing observations in assessing water quality changes when field-based monitoring is hindered and highlights the complex nature of urban estuaries and their heterogeneous response to changes in extreme events and human behavior.

Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.

Functional connectivity reveals different brain networks underlying the idiopathic foreign accent syndrome.

Foreign accent syndrome (FAS) is characterized by new onset speech that is perceived as foreign. Available data from acquired cases suggests focal brain damage in language and sensorimotor brain networks, but little remains known about abnormal functional connectivity in idiopathic cases of FAS without structural damage. Here, connectomic analyses were completed on three patients with idiopathic FAS to investigate unique functional connectivity abnormalities underlying accent change for the first time. Machine learning (ML)-based algorithms generated personalized brain connectomes based on a validated parcellation scheme from the Human Connectome Project (HCP). Diffusion tractography was performed on each patient to rule out structural fiber damage to the language system. Resting-state-fMRI was assessed with ML-based software to examine functional connectivity between individual parcellations within language and sensorimotor networks and subcortical structures. Functional connectivity matrices were created and compared against a dataset of 200 healthy subjects to identify abnormally connected parcellations. Three female patients (28-42 years) who presented with accent changes from Australian English to Irish (n = 2) or American English to British English (n = 1) demonstrated fully intact language system structural connectivity. All patients demonstrated functional connectivity anomalies within language and sensorimotor networks in numerous left frontal regions and between subcortical structures in one patient. Few commonalities in functional connectivity anomalies were identified between all three patients, specifically 3 internal-network parcellation pairs. No common inter-network functional connectivity anomalies were identified between all patients. The current study demonstrates specific language, and sensorimotor functional connectivity abnormalities can exist and be quantitatively shown in the absence of structural damage for future study.

Postoperative Morbidity and Mortality in Lumbar Spine Surgery Patients With Chronic Kidney Disease and Chronic Steroid Use.

BACKGROUND: Perioperative steroids have traditionally been administered during lumbar spine surgery in order to decrease local inflammation and prevent scar tissue formation, which can otherwise contribute to significant, long-lasting postoperative pain due to the formation of epidural fibrosis around lumbar nerve roots. However, the use of steroids in lumbar spine patients has raised concerns of postoperative wound complications caused by corticosteroid-induced immunomodulatory effects and changes in collagen synthesis. Patients with chronic kidney disease (CKD) undergoing spine surgery are at a particularly elevated risk of various complications due to chronic CKD-related systemic inflammation and endothelial dysfunction. It is currently uncertain whether chronic steroid use in CKD patients exerts a protective effect postoperatively due to decreased systemic inflammation or instead is correlated with increased rates of wound complications. RESULTS: Using adjusted odds ratios to control for CKD-related comorbidities, our study of lumbar spine fusion patients who were chronic steroid users vs nonusers found no significant differences in rates of postoperative wound infections in later stage CKD patients. However, we also did not observe statistically significant reductions in hospital length of stay or rates of 30-day mortality, sepsis, or cardiac, pulmonary, and renal events. CONCLUSIONS: Our results indicate chronic steroid use neither contributes significantly to rates of wound infections nor exerts a protective effect against postoperative inflammatory complications in lumbar spine patients with CKD. CLINICAL RELEVANCE: Our findings do not support the practice of holding steroids in chronic users prior to lumbar spine surgery. Perioperative steroids do not appear to increase the risk of postoperative complications, but neither do they improve lumbar spine patient outcomes.

Optical classification of an urbanized estuary using hyperspectral remote sensing reflectance.

Optical water classification based on remote sensing reflectance (Rrs(λ)) data can provide insight into water components driving optical variability and inform the development and application of bio-optical algorithms in complex aquatic systems. In this study, we use an in situ dataset consisting of hyperspectral Rrs(λ) and other biogeochemical and optical parameters collected over nearly five years across a heavily urbanized estuary, the Long Island Sound (LIS), east of New York City, USA, to optically classify LIS waters based on Rrs(λ) spectral shape. We investigate the similarities and differences of discrete groupings (k-means clustering) and continuous spectral indexing using the Apparent Visible Wavelength (AVW) in relation to system biogeochemistry and water properties. Our Rrs(λ) dataset in LIS was best described by three spectral clusters, the first two accounting for the majority (89%) of Rrs(λ) observations and primarily driven by phytoplankton dynamics, with the third confined to measurements in river and river plume waters. We found AVW effective at tracking subtle changes in Rrs(λ) spectral shape and fine-scale water quality features along river-to-ocean gradients. The recently developed Quality Water Index Polynomial (QWIP) was applied to evaluate three different atmospheric correction approaches for satellite-derived Rrs(λ) from the Sentinel-3 Ocean and Land Colour Instrument (OLCI) sensor in LIS, finding Polymer to be the preferred approach. Our results suggest that integrative, continuous indices such as AVW can be effective indicators to assess nearshore biogeochemical variability and evaluate the quality of both in situ and satellite bio-optical datasets, as needed for improved ecosystem and water resource management in LIS and similar regions.

A consensus definition of supratotal resection for anatomically distinct primary glioblastoma: an AANS/CNS Section on Tumors survey of neurosurgical oncologists.

INTRODUCTION: Supratotal resection (SpTR) of glioblastoma may be associated with improved survival, but published results have varied in part from lack of consensus on the definition and appropriate use of SpTR. A previous small survey of neurosurgical oncologists with expertise performing SpTR found resection 1-2 cm beyond contrast enhancement was an acceptable definition and glioblastoma involving the right frontal and bilateral anterior temporal lobes were considered most amenable to SpTR. The general neurosurgical oncology community has not yet confirmed the practicality of this definition. METHODS: Seventy-six neurosurgical oncology members of the AANS/CNS Tumor Section were surveyed, representing 34.0% of the 223 members who were administered the survey. Participants were presented with 11 definitions of SpTR and rated each definition's appropriateness. Participants additionally reviewed magnetic resonance imaging for 10 anatomically distinct glioblastomas and assessed the tumor location's eloquence, perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans. RESULTS: Most neurosurgeons surveyed agree that gross total plus resection of some non-contrast enhancement (n = 57, 80.3%) or resection 1-2 cm beyond contrast enhancement (n = 52, 73.2%) are appropriate definitions for SpTR. Cases were divided into three anatomically distinct groups by perceived equipoise between gross total and SpTR. The best clinical trial candidates were thought to be right anterior temporal (n = 58, 76.3%) and right frontal (n = 55, 73.3%) glioblastomas. CONCLUSION: Support exists among neurosurgical oncologists with varying familiarity performing SpTR to adopt the proposed consensus definition of SpTR of glioblastoma and to potentially investigate the utility of SpTR to treat right anterior temporal and right frontal glioblastomas in a clinical trial. A smaller proportion of general neurosurgical oncologists than SpTR experts would personally treat a left anterior temporal glioblastoma with SpTR.

Theranostic Potential of Adaptive Cold Atmospheric Plasma with Temozolomide to Checkmate Glioblastoma: An In Vitro Study.

Cold atmospheric plasma (CAP) has been used for the treatment of various cancers. The anti-cancer properties of CAP are mainly due to the reactive species generated from it. Here, we analyze the efficacy of CAP in combination with temozolomide (TMZ) in two different human glioblastoma cell lines, T98G and A172, in vitro using various conditions. We also establish an optimized dose of the co-treatment to study potential sensitization in TMZ-resistant cells. The removal of cell culture media after CAP treatment did not affect the sensitivity of CAP to cancer cells. However, keeping the CAP-treated media for a shorter time helped in the slight proliferation of T98G cells, while keeping the same media for longer durations resulted in a decrease in its survivability. This could be a potential reason for the sensitization of the cells in combination treatment. Co-treatment effectively increased the lactate dehydrogenase (LDH) activity, indicating cytotoxicity. Furthermore, apoptosis and caspase-3 activity also significantly increased in both cell lines, implying the anticancer nature of the combination. The microscopic analysis of the cells post-treatment indicated nuclear fragmentation, and caspase activity demonstrated apoptosis. Therefore, a combination treatment of CAP and TMZ may be a potent therapeutic modality to treat glioblastoma. This could also indicate that a pre-treatment with CAP causes the cells to be more sensitive to chemotherapy treatment.

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of cytoreductive surgery in the management of progressive glioblastoma in adults.

QUESTION: In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions? TARGET POPULATION: These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection. RECOMMENDATION: Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival.

Cold Plasma Discharge Tube Enhances Antitumoral Efficacy of Temozolomide.

Glioblastoma (GBM) is a fatal human brain tumor with a low survival rate. Temozolomide (TMZ) has been widely used in GBM therapy with noticeable side effects. Cold plasma is an ionized gas that is generated near room temperature. Here, we demonstrated the enhancement therapeutic efficacy of TMZ via using a cold plasma source based on nonequilibrium plasma in a sealed glass tube, named a radial cold plasma discharge tube (PDT). The PDT affected glioblastoma cells' function just by its electromagnetic (EM) emission rather than any chemical factors in the plasma. The PDT selectively increased the cytotoxicity of TMZ on two typical glioblastoma cell lines, U87MG and A172, compared with normal astrocyte cell line hTERT/E6/E7 to some extent. Furthermore, on the basis of a patient-derived xenograft model, our preliminary in vivo studies demonstrated the drastically improved mean survival days of the tumor-barrier mice by more than 100% compared to control. The PDT is not only independent of continuous helium supply but is also capable of resisting the interference of environmental changes. Thus, the PDT was a stable and low-cost cold atmospheric plasma source. In short, this study is the first to demonstrate the promising application of PDTs in GBM therapy as a noninvasive and portable modality.

Malignant Pineal Parenchymal Tumors in Adults: A National Cancer Database Analysis.

BACKGROUND: Limited retrospective data exist on malignant pineal parenchymal tumors (PPTs) in adults, and there are no large previous studies that review clinical outcomes across the 3 treatment arms of surgery, radiotherapy, and chemotherapy. As a result, optimal disease management has yet to be defined. OBJECTIVE: To evaluate treatment trends and perform survival analysis in adult PPT. METHODS: The National Cancer Database was queried for histologically confirmed PPT diagnosed from 2007 to 2016. Univariate and multivariate Cox regressions were used to evaluate the prognostic impact of covariates. Kaplan-Meier survival curves were generated for comparative subanalyses. RESULTS: Of the 251 patients who met inclusion criteria, 172 had PPTs of intermediate differentiation (PPTID) and 79 had pineoblastoma. A plurality of patients with pineoblastoma were treated with trimodal therapy (39.1%), whereas patients with PPTID were commonly treated with either surgery alone or surgery and radiation (33.7% each). Factors independently associated with improved overall survival include younger patient age, female sex, lower comorbidity score, lower tumor grade, and treatment with surgery or radiation (each P < .05). Subanalyses confirm the effect of radiation on survival in patients with grade III PPTID with subtotal resection; however, no survival benefit of adjuvant radiation is demonstrated in patients with grade II PPTID with subtotal resection. CONCLUSION: Although radiotherapy and surgery were found to increase survival in all patients with PPT, there was no demonstrable survival benefit of adjuvant radiation in surgically treated patients with grade II PPTID. This suggests that adjuvant radiotherapy may not add significant survival benefit in many adult patients with grade II PPTID.

5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study.

OBJECTIVE: Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS: This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS: Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS: PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

Racial Disparities Affecting Postoperative Outcomes After Brain Tumor Resection.

OBJECTIVE: To investigate racial disparities in 30-day postoperative outcomes of craniotomy for glioma resection. METHODS: 2006-2019 American College of Surgeons' National Surgical Quality Improvement Program files were queried for all patients who underwent a craniotomy for a supratentorial glioma resection. Racial disparities in preoperative variables were studied between the demographic cohorts of Asian, African Americans, Hispanics, and Caucasian. Fisher exact tests were used to examine association of preoperative variables with race. Multivariable logistic regression models, adjusted for all preoperative variables associated with race, were used to determine the odds ratios of postoperative outcomes for each demographic cohort in comparison with Caucasian patients. RESULTS: A total of 12,544 patients were identified: 4% Asian, 5% African American, 7% Hispanic, and 85% Caucasian. African American patients had significantly higher adjusted odds than Caucasian patients of major adverse cardiovascular events (adjusted odds ratio [aOR]: 1.827, 95% confidence interval [CI]: 1.155-2.891, P = 0.01), pulmonary events (aOR: 1.683, 95% CI: 1.145-2.473, P = 0.008), and urinary tract infection (aOR: 2.016, 95% CI: 1.221-3.327, P = 0.006). Asian patients had significantly higher odds than Caucasian patients of requiring a transfusion (aOR: 2.094, 95% CI: 1.343-3.266, P = 0.001). All demographic cohorts had higher odds of having an extended length of stay than Caucasian patients. CONCLUSIONS: African American patients who undergo a craniotomy for glioma resection have almost twice the odds of Caucasian patients of having a postoperative major cardiovascular complication, pulmonary complication, or urinary tract infection. All minority groups have higher odds of an extended length of stay as compared with Caucasian patients.

Multi-Modal Biological Destruction by Cold Atmospheric Plasma: Capability and Mechanism.

Cold atmospheric plasma (CAP) is a near-room-temperature, partially ionized gas composed of reactive neutral and charged species. CAP also generates physical factors, including ultraviolet (UV) radiation and thermal and electromagnetic (EM) effects. Studies over the past decade demonstrated that CAP could effectively induce death in a wide range of cell types, from mammalian to bacterial cells. Viruses can also be inactivated by a CAP treatment. The CAP-triggered cell-death types mainly include apoptosis, necrosis, and autophagy-associated cell death. Cell death and virus inactivation triggered by CAP are the foundation of the emerging medical applications of CAP, including cancer therapy, sterilization, and wound healing. Here, we systematically analyze the entire picture of multi-modal biological destruction by CAP treatment and their underlying mechanisms based on the latest discoveries particularly the physical effects on cancer cells.

In Vitro and In Vivo Enhancement of Temozolomide Effect in Human Glioblastoma by Non-Invasive Application of Cold Atmospheric Plasma.

Glioblastoma (GBM) is one of the most aggressive forms of adult brain cancers and is highly resistant to treatment, with a median survival of 12-18 months after diagnosis. The poor survival is due to its infiltrative pattern of invasion into the normal brain parenchyma, the diffuse nature of its growth, and its ability to quickly grow, spread, and relapse. Temozolomide is a well-known FDA-approved alkylating chemotherapy agent used for the treatment of high-grade malignant gliomas, and it has been shown to improve overall survival. However, in most cases, the tumor relapses. In recent years, CAP has been used as an emerging technology for cancer therapy. The purpose of this study was to implement a combination therapy of CAP and TMZ to enhance the effect of TMZ and apparently sensitize GBMs. In vitro evaluations in TMZ-sensitive and resistant GBM cell lines established a CAP chemotherapy enhancement and potential sensitization effect across various ranges of CAP jet application. This was further supported with in vivo findings demonstrating that a single CAP jet applied non-invasively through the skull potentially sensitizes GBM to subsequent treatment with TMZ. Gene functional enrichment analysis further demonstrated that co-treatment with CAP and TMZ resulted in a downregulation of cell cycle pathway genes. These observations indicate that CAP can be potentially useful in sensitizing GBM to chemotherapy and for the treatment of glioblastoma as a non-invasive translational therapy.

Nanoparticles as a Tool in Neuro-Oncology Theranostics.

The rapid growth of nanotechnology and the development of novel nanomaterials with unique physicochemical characteristics provides potential for the utility of nanomaterials in theranostics, including neuroimaging, for identifying neurodegenerative changes or central nervous system malignancy. Here we present a systematic and thorough review of the current evidence pertaining to the imaging characteristics of various nanomaterials, their associated toxicity profiles, and mechanisms for enhancing tropism in an effort to demonstrate the utility of nanoparticles as an imaging tool in neuro-oncology. Particular attention is given to carbon-based and metal oxide nanoparticles and their theranostic utility in MRI, CT, photoacoustic imaging, PET imaging, fluorescent and NIR fluorescent imaging, and SPECT imaging.

Virtual Reality During Brain Mapping for Awake-Patient Brain Tumor Surgery: Proposed Tasks and Domains to Test.

BACKGROUND: Virtual reality (VR) use in health care has increased over the past few decades, with its utility expanding from a teaching tool to a highly reliable neuro-technology adjunct in multiple fields including neurosurgery. Generally, brain tumor surgery with the patient awake has only been performed for mapping of language and motor areas. With the rise of VR and advancing surgical techniques, neurosurgical teams are developing an increased understanding of patients' anatomo-functional connectivity. Consequently, more specific cognitive tasks are being required for the mapping and preservation of deeper layers of cognition. METHODS: An extensive literature review was conducted with the inclusion criteria of manuscripts that described the use of VR during awake neurosurgery mapping. RESULTS: We identified 3 recent articles that met our inclusion criteria, yet none of them addressed the specific use of VR for cognition mapping. Consequently, a cognitive task phase was performed to search and craft the tasks and domains that better filled the spotted niche of this need inside the operating room. A proposed protocol was developed with 5 potential uses of VR for brain mapping during awake neurosurgery, each of them with a specific proposed example of use. CONCLUSIONS: The authors advocate for the use of a VR protocol as a feasible functional tool in awake-patient brain tumor surgery by using it as a complement during cognitive screening in addition to language testing.