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Simple Summary: Glioblastoma is the most common malignant primary brain tumor. Despite technological advancements and modern therapeutic agents used for treatment, the prognosis remains extremely poor. One unique characteristic of glioblastoma is its highly vascularized nature, enabling the tumors to grow and invade the surrounding brain tissue. This process is known as "angiogenesis" which is critical for growth of glioblastoma cells and has been a topic of interest for scientists. A critical protein that facilitates new blood vessel formation is vascular endothelial growth factor-A (VEGF-A), therefore, bevacizumab, a medication that specifically targets VEGF-A has been approved for treatment of recurrent glioblastoma. However, despite its theoretical potential, bevacizumab has failed to offer significant survival improvement. Furthermore, other agents with mechanisms of action comparable to that of bevacizumab have also not been able to demonstrate favorable results. Herein, we review the current state of anti-vascularization therapeutic agents, and the future of this therapeutic approach. Glioblastoma, a WHO grade IV astrocytoma, constitutes approximately half of malignant tumors of the central nervous system. Despite technological advancements and aggressive multimodal treatment, prognosis remains dismal. The highly vascularized nature of glioblastoma enables the tumor cells to grow and invade the surrounding tissue, and vascular endothelial growth factor-A (VEGF-A) is a critical mediator of this process. Therefore, over the past decade, angiogenesis, and more specifically, the VEGF signaling pathway, has emerged as a therapeutic target for glioblastoma therapy. This led to the FDA approval of bevacizumab, a monoclonal antibody designed against VEGF-A, for treatment of recurrent glioblastoma. Despite the promising preclinical data and its theoretical effectiveness, bevacizumab has failed to improve patients' overall survival. Furthermore, several other anti-angiogenic agents that target the VEGF signaling pathway have also not demonstrated survival improvement. This suggests the presence of other compensatory angiogenic signaling pathways that surpass the anti-angiogenic effects of these agents and facilitate vascularization despite ongoing VEGF signaling inhibition. Herein, we review the current state of anti-angiogenic agents, discuss potential mechanisms of anti-angiogenic resistance, and suggest potential avenues to increase the efficacy of this therapeutic approach. [ABSTRACT FROM AUTHOR]

Superior semicircular canal dehiscence (SSCD) is defined by a bony defect overlying the superior semicircular canal (SSC) in the middle cranial fossa floor, causing a myriad of vestibular and auditory symptoms. Patients with thin bone without full dehiscence overlying the SSC also present with similar symptoms. There are currently no guidelines for surgical management of patients with thin bone. The authors offer their experience with thin bone patients to characterize their symptomatology and explore whether these patients benefit from surgical intervention typically offered to SSCD patients. Two hundred fifty-six patients evaluated for SSCD from 2011 to 2019 were reviewed. High-resolution coronal computed tomography scans with 0.6-mm slice thickness of the temporal bones were assessed to determine whether the patient had a true dehiscence or a thin bone covering overlying the SSC. Bone that was ≤0.5 mm was considered to be "thin bone." Parameters of interest included patient demographics as well as preoperative and postoperative symptomatology. A P value < 0.05 was considered statistically significant. Forty-eight patients met inclusion criteria of having "thin bone." The mean age was 48.13 ± 12.03 years, and 65.5% of patients were female. Of the preoperative symptoms evaluated, the greatest postoperative symptomatic resolution was noted in hearing loss (92.3%), vertigo (94.4%), and oscillopsia (100%). Dizziness (56.5%) had the lowest symptomatic resolution rate. Surgical management of thin bone patients via middle fossa craniotomy, a similar technique to SSCD repair, provides significant symptomatic resolution. Therefore, surgery should be considered in thin bone patients with debilitating symptoms, albeit not having a true dehiscence. [ABSTRACT FROM AUTHOR]

The Hispanic community is the most rapidly growing minority group in the United States, making up 18.3% of the population, with 40% reporting limited English proficiency. To address this need, many health sciences institutions have implemented medical Spanish courses to increase Spanish proficiency among future health care providers. Although interactive courses have shown efficacy in teaching field-related terminology, barriers to medical Spanish curriculum implementation persist. Our non-randomized experimental pilot study aims to investigate the benefit of role-play in a medical Spanish course. Nineteen secondyear medical students were recruited to participate. Based on their placement test performance, students were assigned to a beginner or intermediate group, and met weekly for one-hour sessions over five consecutive weeks. Students assumed the roles of Spanish-speaking patient, English-speaking provider, and interpreter to practice various medical scenarios. Students completed pre- and post-course examinations to assess Spanish proficiency improvement. A p-value <0.05 was considered statistically significant. Seven students, all members of the intermediate group, completed the course. Class attendance among this group was 77.4%. When comparing examination scores, there was statistically significant improvement in oral translation of phrases from Spanish to English (p=0.03). Statistically significant improvement in oral translation of phrases from Spanish to English was accomplished through a minimal time requirement of one hour per week utilizing role-play. Given that limited time poses a barrier to implementing medical Spanish curricula, our findings highlight the potential benefit of this teaching methodology with a special emphasis on the under-utilized yet promising modality of role-play and call for its further evaluation. Furthermore, our study demonstrates the necessity of implementing medical Spanish course as an accredited class in medical schools to encourage student participation, which would provide legitimacy to the curriculum as the need for Spanish-speaking doctors increases with the rising Hispanic population in the US. [ABSTRACT FROM AUTHOR]

Superior semicircular canal dehiscence (SSCD) is an abnormality of the otic capsule, which normally overlies the superior semicircular canal. Surgical management is indicated in patients with persistent and debilitating symptoms. Given the complexity of the disease, there are patients who experience less favorable surgical outcomes and require revision surgery. The purpose of this study was to report to the rate of postoperative symptomatic improvement in patients who required revision surgery. A retrospective analysis of patients undergoing SSCD surgical repair at a single institution was performed. Information on patient demographics, primary and secondary surgical approaches, surgical outcomes, and follow-up length was collected. Seventeen patients underwent 20 revision surgeries. There were eleven (65%) females and six (35%) males. Mean age of the cohorts was 50 years (range 30−68 years), and mean follow-up length was 6.8 months (range 0.1−31.1 months). Cerebrospinal fluid leak was noted in 67% of cases. The greatest postoperative symptomatic resolution was reported in oscillopsia (100%), headache (100%), and internal sound amplification (71%), while the least postoperative symptomatic resolution was reported in tinnitus (42%), aural fullness (40%), and dizziness (29%). Revision surgery can provide symptomatic improvement in select SSCD patients; however, patients should be cautioned about the possibility of less favorable outcomes than in index surgery. Revision surgeries are associated with a considerably higher rate of perioperative cerebrospinal fluid leak. [ABSTRACT FROM AUTHOR]

Superior semicircular canal dehiscence (SSCD) is the appearance of a third mobile window between the middle fossa and the superior semicircular canal. Surgical management is indicated in patients with persistent and debilitating symptoms. The purpose of this study was to evaluate the association between preoperative variables that may impact postoperative symptomatic resolution. A single-institution retrospective analysis was performed on patients who were surgically treated for SSCD. Patients were divided to different cohorts based on unilateral or bilateral nature of the disease. A P value <0.05 was considered statistically significant. A total of 229 surgical repairs were analyzed. Mean age was 51 years (± 7.8 years), and 55.9% of patients were female. All cohorts were similar with respect to baseline demographics. The most commonly reported preoperative symptoms were tinnitus, dizziness, and autophony. The greatest symptomatic resolution was seen in autophony, internal sound amplification, hyperacusis, and oscillopsia. The unilateral SSCD cohort had significantly higher improvement of autophony (P = 0.003), aural fullness (P = 0.05), tinnitus (P = 0.006), hearing loss (P = 0.02), dizziness (P = 0.006), and headache (P = 0.007), compared with the bilateral SSCD cohorts. Among patients with bilateral disease, those with unilateral surgery reported greater symptomatic resolution with respect to hyperacusis (P = 0.03), hearing loss (P = 0.02), dizziness (P = 0.03), and disequilibrium (P < 0.001), than those with bilateral operations. Surgical management of SSCD leads to high rates of postoperative symptomatic improvement. Patients with unilateral SSCD benefit greater symptomatic resolution compared to those with bilateral pathology. [ABSTRACT FROM AUTHOR]

Background: Atypical meningiomas (AMs) can have an aggressive clinical course, exhibiting a higher recurrence rate, and portending a worse prognosis than benign meningiomas (BMs). Currently, there remains controversy as to the optimal treatment course for AMs, including the utilization of post-operative radiotherapy. Moreover, the dependence of post-operative adjuvant radiotherapy (ART) dose and its impact on survival is unclear. Objective: In this meta-analysis, we investigate the effect of lower-dose (<55 Gy) vs. higher-dose (³55 Gy) ART following surgical resection on progression free survival (PFS), overall survival (OS), and treatment toxicity complications in AM patients. Methods: In accordance with PRISMA guidelines we queried PubMed, Web of Science, Cochrane, and Scopus databases for studies reporting PFS, OS, and treatment toxicity for intracranial, primary AMs treated with higheror lower-dose ART. Results: Mean 5-year PFS for patients with AM was 73.5% for higher-dose and 70.0% for lower-dose treatments, while 5-year OS was 84.9% and 71.4%, respectively. Only one study reported 5-year OS for a low-dose ART group. ART-induced toxicity incidence for grades III or higher ranged from 0.7% to 19.6% for all AM patients. Conclusion: Our analysis demonstrates no significant difference in 5-year PFS when comparing higher- to lower-dose ART in atypical meningiomas. Importantly, lower radiotherapy dosages may reduce radiation associated complications. Future studies examining surgery + ART should be conducted to more completely elucidate the ideal radiotherapy candidate, modality, and dosage. [ABSTRACT FROM AUTHOR]

Superior semicircular canal dehiscence (SSCD) is an osseous defect of the arcuate eminence of the petrosal temporal bone. Patients typically present with auditory and vestibular symptoms, such as hearing loss and disequilibrium. Using advanced imaging segmentation techniques, we evaluated whether the volume of SSCD correlated with preoperative symptoms and postoperative outcomes. Our laboratory previously described a novel method of quantifying the size of an SSCD via manual segmentation. High-resolution computed tomography images of the temporal bones were imported into a specialized segmentation software. The volume of the dehiscence was outlined on consecutive slices of the coronal and axial planes via a single-pixel-thick paintbrush tool and was then calculated according to the number of nonzero image voxels. This study included 111 patients (70 women and 41 men; mean age, 55.1 years; age range, 24–87 years) with a total of 164 SSCDs. Mean postoperative follow-up time was 5.2 months (range, 0.03–59.5 months). The most common preoperative and postoperative symptoms were tinnitus (n = 85) and dizziness (n = 45), respectively. Surgery resulted in improvement of symptoms in most patients. The average volume of 164 SSCDs was 1.3 mm3. SSCD volume was not significantly associated with either preoperative symptoms or postoperative outcomes. Advances in imaging techniques have allowed increased visualization of SSCD. Further research will be necessary to evaluate the potential correlation of volume of the dehiscence with clinical variables. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to identify baseline clinical and radiological characteristics of brain metastases (BMs) associated with a higher probability of lesion-specific progression-free survival (PFS-L) after laser interstitial thermal therapy (LITT)., Methods: A total of 47 lesions in 42 patients with BMs treated with LITT were retrospectively examined, including newly diagnosed BM, suspected recurrent BM, and suspected radiation necrosis. The association of baseline clinical and radiological features with PFS-L was assessed using survival analyses. Radiological features included lesion size measurements, diffusion and perfusion metrics, and sphericity, which is a radiomic feature ranging from 1 (perfect sphere) to 0., Results: The probability of PFS-L for the entire cohort was 88.0% at 3 months, 70.6% at 6 months, 67.4% at 1 and 2 years, and 62.2% at 3 years. For lesions progressing after LITT (n = 13), the median time to progression was 3.9 months, and most lesions (n = 11) progressed within 6 months after LITT. In lesions showing response to LITT (n = 17), the median time to response was 12.1 months. All 3 newly diagnosed BMs showed a long-term response. The mean (± SD) follow-up duration for all censored lesions (n = 34) was 20.7 ± 19.4 months (range 12 days to 6.1 years). The mean pretreatment enhancing volume was 2.68 cm3 and the mean sphericity was 0.70. Pretreatment small enhancing volume (p = 0.003) and high sphericity (p = 0.024) computed from lesion segmentation predicted a longer PFS-L after LITT. Lesions meeting optimal cutoffs of either enhancing volume < 2.5 cm3 (adjusted p = 0.004) or sphericity ≥ 0.705 (adjusted p = 0.019) had longer PFS-L, and their probability of PFS-L was 86.8% at 3 years. Lesions meeting both cutoffs showed a cumulative benefit (p < 0.0001), with a 100% probability of PFS-L at 3 years, which was unchanged at the end of follow-up (4.1 years). Manually computed estimates of lesion size (maximal axial diameter, p = 0.011) and sphericity (p = 0.043) were also predictors of PFS-L. Optimal cutoffs of diameter < 2 cm (adjusted p = 0.035) or manual sphericity ≥ 0.91 (adjusted p = 0.092) identified lesions with longer PFS-L, and lesions meeting both cutoffs showed a cumulative benefit (p = 0.0023). Baseline diffusion imaging did not predict PFS-L. A subset of lesions (n = 7) with highly perfused hotspots had worse PFS-L (adjusted p = 0.010), but perfusion signal contamination from vessels and cortex and underlying size differences were possible confounders., Conclusions: Small size and high sphericity are ideal baseline features for lesions considered for LITT treatment, with a cumulative PFS-L benefit when both features are present, that could aid patient selection.

Introduction The use of magnetoencephalography (MEG) in localizing epileptic foci and directing surgical treatment of medically refractory epilepsy is well established in clinical practice; however, it has not yet been incorporated into the routine planning of stereo-electroencephalography (EEG) (SEEG) depth electrode trajectories during invasive intracranial evaluation for epileptic foci localization. In this study, we assess the impact of MEG-directed SEEG on seizure outcomes in a pediatric cohort. Methods A retrospective analysis was performed on a single-institution cohort of pediatric patients with medically refractory epilepsy who underwent epilepsy surgery. The primary endpoint was the reduction in seizure burden as determined by dichotomized Engel scores (favorable outcome: Engel scores I and II; poor outcome: Engel scores III and IV). Results Thirty-seven patients met the inclusion criteria (24 males and 13 females). The median age at seizure onset was three years, the median age at surgery was 14.1 years, and the median follow-up length was 30.8 months. Concordance was noted in 7/10 (70%) patients who received MEG-directed SEEG. Good clinical outcomes were achieved in 70% of MEG-directed SEEG patients, compared to 59.4% in their counterparts; however, this difference was not statistically significant (p=0.72). We noted no statistically significant association between sex, disease laterality, or age at surgery and good clinical outcomes. Conclusions Patients who underwent MEG-directed SEEG had favorable clinical outcomes, which demonstrated the practicability of this technique for determining SEEG electrode placement. Although no significant difference in clinical outcomes was obtained between the two groups, this may have been due to low statistical power. Future prospective, multi-institutional investigations to assess the benefit of MEG-directed SEEG are warranted., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Mozaffari et al.)

Aim: To compare the perioperative outcomes between single-day combined or separate-day staged surgeries for cervical spinal stenosis., Material and Methods: A retrospective cohort analysis was conducted on consecutive patients admitted at a single institution between July 2015 and April 2019, who underwent either single-day combined or separate-day staged surgeries during the same hospitalization period. Demographics, comorbidities, hospital length of stay, and perioperative complications were compared between the patient groups., Results: Eighty patients (combined surgery: n=68, staged surgery: n=12) were included. Dysphagia was the most commonly reported postoperative complication in 44/80 patients (55%). There were no significant differences in the baseline demographics between the two groups. The staged surgery group had significantly longer total time in the operating room (7.2 vs. 8.5 hours, p=0.002), longer duration of general anesthesia (6.7 vs. 7.6 hours, p=0.006), and higher incidence of postoperative delirium (12.1% vs. 50% p=0.005) than the combined surgery group. The mean hospital length of stay was similar in the two groups (combined surgery: 7.5 days vs. staged surgery: 15.1 days, p=0.09)., Conclusion: Staged anterior and posterior cervical decompressions, stabilizations, and fusions are associated with longer total time in the operating room, longer duration of general anesthesia, and higher incidence of postoperative delirium than combined surgeries.

Traumatic brain injury (TBI) is responsible for the majority of trauma-related deaths and is a leading cause of disability. It is characterized by an inflammatory process involved in the progression of secondary brain injury. TBI is measured by the Glasgow Coma Scale (GCS) with scores ranging from 15-3, demonstrating mild to severe brain injury. Apart from this clinical assessment of TBI, compendiums of literature have been published on TBI-related serum markers.Herein we create a comprehensive appraisal of the most prominent serum biomarkers used in the assessment and care of TBI.The PubMed, Scopus, Cochrane, and Web of Science databases were queried with the terms "biomarker" and "traumatic brain injury" as search terms with only full-text, English articles within the past 10 years selected. Non-human studies were excluded, and only adult patients fell within the purview of this analysis. A total of 528 articles were analyzed in the initial search with 289 selected for screening. A further 152 were excluded for primary screening. Of the remaining 137, 54 were included in the final analysis. Serum biomarkers were listed into the following broad categories for ease of discussion: immune markers and markers of inflammation, hormones as biomarkers, coagulation and vasculature, genetic polymorphisms, antioxidants and oxidative stress, apoptosis and degradation pathways, and protein markers. Glial fibrillary acidic protein(GFAP), S100, and neurons specific enolase (NSE) were the most prominent and frequently cited markers. Amongst these three, no single serum biomarker demonstrated neither superior sensitivity nor specificity compared to the other two, therefore noninvasive panels should incorporate these three serum biomarkers to retain sensitivity and maximize specificity for TBI., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2021, Mozaffari et al.)