We Tabulated and Organized American Board of Neurological Surgeons Primary Exam Keywords (2015-2023) so You Don't Have to.

Background Passing the American Board of Neurological Surgeons (ABNS) Primary Exam is required for residents in training. Both the program directors and residents are given keywords of the exam afterward in the hope to help program directors determine their relative strengths and weakness. We have organized and tabulated these keywords for neurosurgery residents' benefit. Methodology We collected and analyzed ABNS Primary Exam keywords (2015-2023) in each of the exam's main categories for trends and recurrences. We examined the overall passing rates among first-time credit test takers. The frequency of each subcategory was calculated as a percentage within its corresponding category. Recurrent keywords were grouped together with their corresponding years and categorized as once, twice, or thrice and greater occurrences; the last category was considered to be high-yield keywords. Results The number of questions in Neurosciences and Neurology has decreased over the years while Neurosurgery and Critical Care questions have increased. Similarly, there are fewer keyword repeats in Neurosciences and Neurology. The most repeated keywords are in Neuroimaging. The most common keywords are presented and listed along with the years of occurrences. Overall, the passing rate among first-time credit test takers is over 90%. Conclusions Neurosurgery residents can consider the common keywords as a guide in preparation for the ABNS Primary Exam.

Educational impact of early COVID-19 operating room restrictions on neurosurgery resident training in the United States: A multicenter study.

BACKGROUND: The coronavirus (COVID-19) pandemic has caused unprecedented suspensions of neurosurgical elective surgeries, a large proportion of which involve spine procedures. The goal of this study is to report granular data on the impact of early COVID-19 pandemic operating room restrictions upon neurosurgical case volume in academic institutions, with attention to its secondary impact upon neurosurgery resident training. This is the first multicenter quantitative study examining these early effects upon neurosurgery residents caseloads. METHODS: A retrospective review of neurosurgical caseloads among seven residency programs between March 2019 and April 2020 was conducted. Cases were grouped by ACGME Neurosurgery Case Categories, subspecialty, and urgency (elective vs. emergent). Residents caseloads were stratified into junior (PGY1-3) and senior (PGY4-7) levels. Descriptive statistics are reported for individual programs and pooled across institutions. RESULTS: When pooling across programs, the 2019 monthly mean (SD) case volume was 214 (123) cases compared to 217 (129) in January 2020, 210 (115) in February 2020, 157 (81), in March 2020 and 82 (39) cases April 2020. There was a 60% reduction in caseload between April 2019 (207 [101]) and April 2020 (82 [39]). Adult spine cases were impacted the most in the pooled analysis, with a 66% decrease in the mean number of cases between March 2020 and April 2020. Both junior and senior residents experienced a similar steady decrease in caseloads, with the largest decreases occurring between March and April 2020 (48% downtrend). CONCLUSIONS: Results from our multicenter study reveal considerable decreases in caseloads in the neurosurgical specialty with elective adult spine cases experiencing the most severe decline. Both junior and senior neurosurgical residents experienced dramatic decreases in case volumes during this period. With the steep decline in elective spine cases, it is possible that fellowship directors may see a disproportionate increase in spine fellowships in the coming years. In the face of the emerging Delta and Omicron variants, programs should pay attention toward identifying institution-specific deficiencies and developing plans to mitigate the negative educational effects secondary to such caseloads reduction.

[Retracted] Metabolic remodeling precedes mitochondrial outer membrane permeabilization in human glioma xenograft cells.

Following the publication of the above paper, we were contacted by the University of Illinois at Chicago, to request the retraction of the above article. Following a formal institutional investigation, the investigation panel concluded that the images in question had falsifying elements. Regarding the above study, the specific allegations that were investigated were that of falsifying elements of Fig. 6A, row 2, columns 2 and 3. Following a review of this paper conducted independently by the Editor of International Journal of Oncology, the Editor concurred with the conclusions of the investigation panel, and therefore the above paper has been retracted from the publication. We also tried to contact the authors, but did not receive a reply. The Editor apologizes to the readership for the inconvenience caused.[the original article was published in International Journal of Oncology 40: 509­518, 2012; DOI: 10.3892/ijo.2011.1255].

Vertebral body fracture after anterior cervical discectomy and fusion with zero-profile anchored cages in adjacent levels: a cautionary tale.

BACKGROUND CONTEXT: Zero-profile (also called self-locking, anchored or stand-alone cages) have been recently proposed as an interesting alternative for anterior cervical discectomy and fusion (ACDF), as they are supposed to reduce the rates of post-operative cage extrusion without necessarily incurring in the additional surgical time and increased rates of dysphagia associated with plating. Nevertheless, the exact indications of zero-profile anchored cages have not yet been established in the literature. PURPOSE: To report the first case of a vertebral body fracture between the blades of zero-profile anchored cages after ACDFs in adjacent levels and to review the available literature on hardware-related complications after multi-level ACDFs with zero-profile anchored cages. STUDY DESIGN: Case report and systematic literature review. METHODS: The authors report the first case of a vertebral body fracture between the blades of zero-profile anchored cages after ACDFs in adjacent levels. The patient presented with refractory mechanical neck pain at the 1-month post-operative follow-up, ultimately requiring a posterior instrumented fusion. A comprehensive systematic literature review on the available data regarding the safety, complications as well as radiological and clinical outcomes of zero-profile anchored cages is also performed. RESULTS: In the reported case, the use of zero-profile anchored cages in adjacent levels on the cervical spine led to a fracture of the vertebral body between the cages at the 1-month follow-up, with anterior avulsion of the part of the vertebral body where the blades from the two cages converged. According to the systematic literature review which included 409 patients from 10 different clinical series (with a total cumulative follow-up of approximately 535 patients-year), there were only two reported hardware-related complications after ACDF with zero-profile anchored cages, none of them involving fracture at the level of convergence of blades or screws. CONCLUSIONS: Although hardware-related complications after the use of zero-profile anchored cages seem to be rare events, future biomechanical and clinical studies are warranted in order to evaluate the safety of employing such devices for the treatment of multilevel degenerative disc disease in the cervical spine.

Five-year Results of a Randomized Controlled Trial for Lumbar Artificial Discs in Single-level Degenerative Disc Disease.

STUDY DESIGN: A prospective, multicenter, randomized, controlled, investigational device exemption (IDE) noninferiority trial. OBJECTIVE: The aim of this study was to compare the 5-year safety and effectiveness of the activL Artificial Disc with Control Total Disc Replacement (TDR) systems (ProDisc-L or Charité) in the treatment of patients with symptomatic single-level lumbar degenerative disc disease (DDD). SUMMARY OF BACKGROUND DATA: The activL Artificial Disc received Food and Drug Administration approval in 2015 based on 2-year follow-up data. METHODS: Eligible patients presented with symptomatic, single-level, lumbar DDD who failed ≥6 months of nonsurgical management. At entry, 324 patients were randomly allocated (2 : 1) to treatment with activL (n = 218) or Control (n = 106, including n = 65 ProDisc-L and n = 41 Charité) TDR. At 5-year follow up, a total of 261 patients (176 activL patients and 85 Control patients) were available for analysis. RESULTS: The primary composite endpoint at 5 years for activL patients was noninferior to Control TDR. Relative to baseline, reductions in back pain severity and improvements in Oswestry Disability Index (ODI) were maintained for both the activL and Control TDR groups through 5 years. The activL group showed significantly better range of motion for flexion-extension rotation, flexion-extension translation, and disc angle, compared with Control TDR. Freedom from a serious adverse event through 5 years was 64% in activL patients, 47% in Control patients (log-rank P = 0.0068). Freedom from index-level and adjacent-level reoperation was high for TDR patients, ranging between 94% and 99%, respectively. CONCLUSION: Long-term evidence supports lumbar total disc replacement as safe. The next-generation activL Artificial Disc is more effective at preserving range of motion than first-generation lumbar TDRs (ProDisc-L and Charité) and offers a higher safety profile. Other primary and secondary outcomes are similar between disc designs. LEVEL OF EVIDENCE: 2.

The 'Lumbar Fusion Outcome Score' (LUFOS): a new practical and surgically oriented grading system for preoperative prediction of surgical outcomes after lumbar spinal fusion in patients with degenerative disc disease and refractory chronic axial low back pain.

In order to evaluate the predictive effect of non-invasive preoperative imaging methods on surgical outcomes of lumbar fusion for patients with degenerative disc disease (DDD) and refractory chronic axial low back pain (LBP), the authors conducted a retrospective review of 45 patients with DDD and refractory LBP submitted to anterior lumbar interbody fusion (ALIF) at a single center from 2007 to 2010. Surgical outcomes - as measured by Visual Analog Scale (VAS/back pain) and Oswestry Disability Index (ODI) - were evaluated pre-operatively and at 6 weeks, 3 months, 6 months, and 1 year post-operatively. Linear mixed-effects models were generated in order to identify possible preoperative imaging characteristics (including bone scan/99mTc scintigraphy increased endplate uptake, Modic endplate changes, and disc degeneration graded according to Pfirrmann classification) which may be predictive of long-term surgical outcomes . After controlling for confounders, a combined score, the Lumbar Fusion Outcome Score (LUFOS), was developed. The LUFOS grading system was able to stratify patients in two general groups (Non-surgical: LUFOS 0 and 1; Surgical: LUFOS 2 and 3) that presented significantly different surgical outcomes in terms of estimated marginal means of VAS/back pain (p = 0.001) and ODI (p = 0.006) beginning at 3 months and continuing up to 1 year of follow-up. In conclusion,  LUFOS has been devised as a new practical and surgically oriented grading system based on simple key parameters from non-invasive preoperative imaging exams (magnetic resonance imaging/MRI and bone scan/99mTc scintigraphy) which has been shown to be highly predictive of surgical outcomes of patients undergoing lumbar fusion for treatment for refractory chronic axial LBP.

Lumbar Total Disc Replacement for Discogenic Low Back Pain: Two-year Outcomes of the activL Multicenter Randomized Controlled IDE Clinical Trial.

STUDY DESIGN: A prospective, multicenter, randomized, controlled, investigational device exemption (IDE) noninferiority trial. OBJECTIVE: The aim of this study was to evaluate the comparative safety and effectiveness of lumbar total disc replacement (TDR) in the treatment of patients with symptomatic degenerative disc disease (DDD) who are unresponsive to nonsurgical therapy. SUMMARY OF BACKGROUND DATA: Lumbar TDR has been used to alleviate discogenic pain and dysfunction while preserving segmental range of motion and restoring stability. There is a paucity of data available regarding the comparative performance of lumbar TDR. METHODS: Patients presenting with symptomatic single-level lumbar DDD who failed at least 6 months of nonsurgical management were randomly allocated (2:1) to treatment with an investigational TDR device (activL, n = 218) or FDA-approved control TDR devices (ProDisc-L or Charité, n = 106). The hypothesis of this study was that a composite effectiveness outcome at 2 years in patients treated with activL would be noninferior (15% delta) to that in controls. RESULTS: The primary composite endpoint of this study was met, which demonstrated that the activL TDR was noninferior to control TDR (P < 0.001). A protocol-defined analysis of the primary composite endpoint also confirmed that activL was superior to controls (P = 0.02). Radiographic success was higher with activL versus controls (59% vs. 43%; P < 0.01). Mean back pain severity improved by 74% with activL and 68% with controls. Oswestry Disability Index scores decreased by 67% and 61% with activL and controls, respectively. Patient satisfaction with treatment was over 90% in both groups at 2 years. Return to work was approximately 1 month shorter (P = 0.08) with activL versus controls. The rate of device-related serious adverse events was lower in patients treated with activL versus controls (12% vs. 19%; P = 0.13). Surgical reintervention rates at the index level were comparable (activL 2.3%, control 1.9%). CONCLUSION: The single-level activL TDR is safe and effective for the treatment of symptomatic lumbar DDD through 2 years. LEVEL OF EVIDENCE: 2.

Acute Spinal Subdural Hematoma after Vertebroplasty: A Case Report Emphasizing the Possible Etiologic Role of Venous Congestion.

Study Design Case report and literature review. Objective Spinal subdural hematomas are rare events that often progress with severe neurologic deficits. Although there have been several case reports in the literature of spontaneous spinal subdural hematomas in the setting of anticoagulation, antiplatelet therapy, or coagulation disorders, the exact pathophysiology of such phenomena remains obscure. Methods We present the first report of a subdural hematoma after a percutaneous vertebroplasty and provide a comprehensive review on the anatomy of venous drainage of the vertebral bodies with emphasis on the possible effects of venous congestion caused by cement obstruction. Results Because the subdural hematoma occurred in the absence of major cement extravasation to the spinal canal and two levels above the site of the vertebroplasty, we discuss the possible role of venous congestion as the main etiologic factor leading to rupture of the fragile, valveless radiculomedullary veins into the subdural space. Conclusions The reported case supports a possible new pathophysiological scheme for the development of spinal subdural hematoma in which venous congestion plays a pivotal etiologic role. The reported findings suggests that future anatomical and histologic studies investigating the response of the radiculomedullary veins to congestive venous hypertension may shed new light into the pathophysiology of spinal subdural hematomas.

Transdifferentiation of differentiated stem cells contributes to remyelination.

Evidence suggests that transdifferentiation of mesenchymal stem cells (MSCs) into various neuronal cells contributes to functional recovery after experimental spinal cord injury. Qiu et al. have recently published an exciting article in Stem Cell Research & Therapy demonstrating the transdifferentiation of already differentiated MSCs that contributes to remyelination of injured/regenerating axons, and thereby to functional recovery of spinal cord injured animals. The authors highlight the importance of interaction between neurotrophin-3 and tropomyosin receptor kinase C for the observed effects. This study provided important evidence that manipulation of rat bone marrow-derived MSCs before transplantation could enhance the therapeutic benefit of cell-based treatment.

Mesenchymal stem cells in the treatment of spinal cord injuries: A review.

With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. Recent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.

Radiation-induced hypomethylation triggers urokinase plasminogen activator transcription in meningioma cells.

Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H(2)O(2) or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers uPA expression in meningioma cells.

Cathepsin B and uPAR regulate self-renewal of glioma-initiating cells through GLI-regulated Sox2 and Bmi1 expression.

Cancer-initiating cells comprise a heterogeneous population of undifferentiated cells with the capacity for self-renewal and high proliferative potential. We investigated the role of uPAR and cathepsin B in the maintenance of stem cell nature in glioma-initiating cells (GICs). Simultaneous knockdown of uPAR and cathepsin B significantly reduced the expression of CD133, Nestin, Sox2 and Bmi1 at the protein level and GLI1 and GLI2 at the messenger RNA level. Also, knockdown of uPAR and cathepsin B resulted in a reduction in the number of GICs as well as sphere size. These changes are mediated by Sox2 and Bmi1, downstream of hedgehog signaling. Addition of cyclopamine reduced the expression of Sox2 and Bmi1 along with GLI1 and GLI2 expression, induced differentiation and reduced subsphere formation of GICs thereby indicating that hedgehog signaling acts upstream of Sox2 and Bmi1. Further confirmation was obtained from increased luciferase expression under the control of a GLI-bound Sox2 and Bmi1 luciferase promoter. Simultaneous knockdown of uPAR and cathepsin B also reduced the expression of Nestin Sox2 and Bmi1 in vivo. Thus, our study highlights the importance of uPAR and cathepsin B in the regulation of malignant stem cell self-renewal through hedgehog components, Bmi1 and Sox2.

Apoptosis induced by knockdown of uPAR and MMP-9 is mediated by inactivation of EGFR/STAT3 signaling in medulloblastoma.

BACKGROUND: Medulloblastoma is a highly invasive cancer of central nervous system diagnosed mainly in children. Matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator receptor (uPAR) are over expressed in several cancers and well established for their roles in tumor progression. The present study is aimed to determine the consequences of targeting these molecules on medulloblastoma progression. METHODOLOGY/PRINCIPAL FINDINGS: Radiation is one of the foremost methods applied for treating cancer and considerable evidence showed that radiation elevated uPAR and MMP-9 expression in medulloblastoma cell. Therefore efforts are made to target these molecules in non-irradiated and irradiated medulloblastoma cells. Our results showed that siRNA-mediated knockdown of uPAR and MMP-9, either alone or in combination with radiation modulated a series of events leading to apoptosis. Down regulation of uPAR and MMP-9 inhibited the expression of anti-apoptotic molecules like Bcl-2, Bcl-xL, survivin, XIAP and cIAPI; activated BID cleavage, enhanced the expression of Bak and translocated cyctochrome C to cytosol. Capsase-3 and -9 activities were also increased in uPAR- and MMP-9-downregulated cells. The apoptosis induced by targeting MMP-9 and uPAR was initiated by inhibiting epidermal growth factor receptor (EGFR) mediated activation of STAT3 and NF-κB related signaling molecules. Silencing uPAR and MMP-9 inhibited DNA binding activity of STAT3 and also reduced the recruitment of STAT3 protein at the promoter region of Bcl-2 and survivin genes. Our results suggest that inhibiting uPAR and MMP-9 reduced the expression of anti-apoptotic molecules by inactivating the transcriptional activity of STAT3. In addition, treating pre-established medulloblastoma with siRNAs against uPAR and MMP-9 both alone or in combination with radiation suppressed uPAR, MMP-9, EGFR, STAT3 expression and induced Bak activation leading to apoptosis. CONCLUSION/SIGNIFICANCE: Taken together, our results illustrated that RNAi mediated targeting of uPAR and MMP-9 might have therapeutic potential against medulloblastoma.

Blockade of SOX4 mediated DNA repair by SPARC enhances radioresponse in medulloblastoma.

SPARC is a matricellular glycoprotein and a putative radioresistance-reversal-gene. We therefore explored the possibility of SPARC expression on medulloblastoma radiosensitivity in vitro and in vivo. The combined treatment of the SPARC and irradiation resulted in increased cell death when compared to cells treated with irradiation alone in vitro and in vivo. SPARC expression prior to irradiation suppressed checkpoints-1,-2 and p53 phosphorylation and DNA repair gene XRCC1. We also demonstrate that SPARC expression suppressed irradiation induced SOX-4 mediated DNA repair. These results provide evidence of the anti-tumor effect of combining SPARC with irradiation as a new therapeutic strategy for the treatment of medulloblastoma.

RETRACTED: MMP-9 induces CD44 cleavage and CD44 mediated cell migration in glioblastoma xenograft cells.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor in Chief. On behalf the University of Illinois at Chicago, the Associate Vice Chancellor and Research Integrity Officer requested retraction of the article because of the elements listed here that were deemed false: Figure 5B, bottom row, Columns 1, 2, 4 and 5, top panel; Figure 5B, Row 1, Columns 1 and 2, bottom panel; Figure 5B, Row 2, Columns 3 and 4 bottom panel. Based on these circumstances the Editor in Chief has therefore decided to retract the paper. The corresponding author has been non-responsive to approaches from the Publisher.

uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are postulated to play key roles in glioma invasion. Calcineurin is one of the key regulators of mitochondrial-dependent apoptosis, but its mechanism is poorly understood. Hence, we studied subcellular localization of calcineurin after transcriptional downregulation of uPAR and cathepsin B in glioma. In the present study, efficient downregulation of uPAR and cathepsin B increased the translocation of calcineurin A from the mitochondria to the cytosol, decreased pBAD (S136) expression and its interaction with 14-3-3ζ and increased the interaction of BAD with Bcl-xl. Co-depletion of uPAR and cathepsin B induced mitochondrial translocation of BAD, activation of caspase 3 as well as PARP and cytochrome c and SMAC release. These effects were inhibited by FK506 (10 µM), a specific inhibitor of calcineurin. Calcineurin A was co-localized and also co-immunoprecipitated with Bcl-2. This interaction decreased with co-depletion of uPAR and cathepsin B and also with Bcl-2 inhibitor, HA 14-1 (20 µg/ml). Altered localization and interaction of calcineurin A with Bcl-2 was also observed in vivo when uPAR and cathepsin B were downregulated. In conclusion, downregulation of uPAR and cathepsin B induced apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.