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  • Commentary: Predicting Postoperative Outcomes in Brain Tumor Patients With a 5-Factor Modified Frailty Index. Neurosurgery Zhang, M., Hayden Gephart, M., Zygourakis, C. C. 2020

    View details for DOI 10.1093/neuros/nyaa407

    View details for PubMedID 32888308

  • Extraforaminal Vertebral Artery Anomalies and their Associated Surgical Implications: an epidemiological and anatomic report on 1000 patients. World neurosurgery Zhang, M., Dayani, F., Purger, D. A., Cage, T., Lee, M., Patel, M., Singh, H. 2020

    Abstract

    OBJECTIVE: Extraforaminal vertebral anomalies involve entry at cervical transverse foramina other than at C6 and can appear with other anatomical variations along the V2 segment. Such unexpected vessel courses can have implications on surgical planning. We sought to evaluate the incidence of anomalous V2 segment entries, as well as their associations with vessel dominance, medialization, and C7 pedicle width.METHODS: We conducted a retrospective study on 1000 consecutive computed tomography angiograms, documenting level and laterality of vessel of entry, as well as vertebral dominance patterns. Patients with rostral C4 anomalies were assessed for medialization. The pedicle widths ipsilateral to caudal C7 anomalies were compared to those of contralateral and matched controls.RESULTS: A total of 157 patients were identified with extraforaminal entries, with 25 having bilateral findings. The most common alternative entry was at C5 (70.3%), followed by C4 (17.6%) and C7 (11.5%). Among patients with unilateral anomalies, there was an increased representation of contralateral vertebral dominance, relative to ipsilateral dominance (79.6% vs 20.4%, p < 0.0001). Among anomalous C4 entries, vertebral medialization was seen along the right (35%) and left sides (23.1%) spanning C6-T1. Among C7 anomalous entries there was no statistical difference in pedicle width.CONCLUSIONS: Extraforaminal anomalies may be more frequent than previously reported and are important considerations during subaxial cervical spine surgery planning. Particular attention should be paid towards the contralateral dominance pattern within this subgroup. In patients with anomalous V2 segment entries, adherence to the standard, anatomical landmarks remains desirable.

    View details for DOI 10.1016/j.wneu.2020.06.110

    View details for PubMedID 32585381

  • Boda Bodas and Road Traffic Injuries in Uganda: An Overview of Traffic Safety Trends from 2009 to 2017. International journal of environmental research and public health Vaca, S. D., Feng, A. Y., Ku, S., Jin, M. C., Kakusa, B. W., Ho, A. L., Zhang, M., Fuller, A., Haglund, M. M., Grant, G. 2020; 17 (6)

    Abstract

    INTRODUCTION: Road traffic injuries (RTIs) are an important contributor to the morbidity and mortality of developing countries. In Uganda, motorcycle taxis, known as boda bodas, are responsible for a growing proportion of RTIs. This study seeks to evaluate and comment on traffic safety trends from the past decade.METHODS: Traffic reports from the Ugandan police force (2009 to 2017) were analyzed for RTI characteristics. Furthermore, one month of casualty ward data in 2015 and 2018 was collected from the Mulago National Referral Hospital and reviewed for casualty demographics and trauma type.RESULTS: RTI motorcycle contribution rose steadily from 2009 to 2017 (24.5% to 33.9%). While the total number of crashes dropped from 22,461 to 13,244 between 2010 and 2017, the proportion of fatal RTIs increased from 14.7% to 22.2%. In the casualty ward, RTIs accounted for a greater proportion of patients and traumas in 2018 compared to 2015 (10%/41% and 36%/64%, respectively).CONCLUSIONS: Although RTIs have seen a gross reduction in Uganda, they have become more deadly, with greater motorcycle involvement. Hospital data demonstrate a rising need for trauma and neurosurgical care to manage greater RTI patient burden. Combining RTI prevention and care pathway improvements may mitigate current RTI trends.

    View details for DOI 10.3390/ijerph17062110

    View details for PubMedID 32235768

  • Commentary: The Effects of Postoperative Neurological Deficits on Survival in Patients With Single Brain Metastasis. Operative neurosurgery (Hagerstown, Md.) Zhang, M., Li, G. 2020

    View details for DOI 10.1093/ons/opaa267

    View details for PubMedID 32860056

  • Elevated risk of venous thromboembolism among post-traumatic brain injury patients requiring pharmaceutical immobilization. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Zhang, M., Parikh, B., Dirlikov, B., Cage, T., Lee, M., Singh, H. 2020

    Abstract

    Traumatic brain injury (TBI) patients are known to have a high rate of venous thromboembolism (VTE), and additional neuromuscular blockade or barbiturate coma therapy has the theoretical risk of exacerbating baseline hemostasis and elevating the incidence of thromboembolic events. We conducted a single-institution retrospective review of patients surviving severe TBI, as determined by need for intracranial pressure (ICP) monitoring, who further required paralytics or barbiturate therapy to maintain ICP control. Patients were administered VTE prophylaxis as clinically appropriate. Predictors for VTE were subsequently determined with univariate and logistic multivariate regression analyses. The main cohort includes 144 patients, 34 of whom received pharmaceutical immobilization for ICP control. Mean ISS and GCS at intake were 31.9 and 5.2, respectively. Among those receiving vs not-receiving paralytics and/or barbiturate therapy, there was a statistical difference of 12/34 (35.3%) vs 18/110 (16.4%, pá=á0.0280) in VTE events, at a mean time greater than two weeks from the time of trauma. Multivariate logistics regression indicated 3.2 times increased odds of developing a VTE (log oddsá=á1.17, pá=á0.023). No pediatric patients were positive for an event (0/12 vs 7/22, pá=á0.0356), and infections were only documented among those with VTE (0/22 vs 4/12, pá=á0.0107). Overall, paralytics and barbiturate therapy were correlated with a higher incidence of VTE among TBI patients. Although the need for ICP control will outweigh an increase in thromboembolic risk, there is value for increased surveillance and screening during the prolonged inpatient stay of these patients.

    View details for DOI 10.1016/j.jocn.2020.03.028

    View details for PubMedID 32245600

  • Costs and Complications Associated with Resection of Supratentorial Tumors with and without the Operative Microscope in the United States. World neurosurgery Zhang, Y., Zhang, M., Lin, M., Gephart, M. H., Veeravagu, A., Ratliff, J. K., Li, G. 2020

    Abstract

    The operative microscope, a commonly used tool in neurosurgery, is critical in many supratentorial tumor cases. However, use of operating microscope for supratentorial tumor varies by surgeon.To assess complication rates, readmissions, and costs associated with operative microscope use in supratentorial resections.A retrospective analysis was conducted using a national administrative database to identify patients with glioma or brain metastases who underwent supratentorial resection between 2007 and 2016. Univariate and multivariate analyses were used to assess 30-day complications, readmissions and costs between patients who underwent resection with and without use of microscope.The cohort included 12058 glioma patients and 5433 metastasis patients. Rates of microscope use varied by state from 19.0% to 68.6%. Microscope use was associated with $5228.9 in additional costs of index hospitalization among glioma patients (p < 0.001), and $2824.0 among metastasis patients (p < 0.001). Rates of intraoperative cerebral edema were lower among the microscope cohort than among the non-microscope cohort (p < 0.027). Microscope use was associated with a slight reduction in 30-day rates of neurological complications (14.7% vs. 16.7%, p = 0.048), specifically in nonspecific cerebrovascular complications. There were no differences in rates of other complications, readmissions, or 30-day postoperative costs.Use of operative microscope for supratentorial resections varies by state and is associated with higher cost of surgery. Microscope use may be associated with lower rates of intraoperative cerebral edema and some cerebrovascular complications, but is not associated with significant differences in other complications, readmissions, or 30-day costs.

    View details for DOI 10.1016/j.wneu.2020.03.021

    View details for PubMedID 32171932

  • Intracranial Tumor Control Following Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma. World neurosurgery Zhang, M., Rodrigues, A. J., Bhambhvani, H. P., Fatemi, P., Pollom, E. L., Gibbs, I. C., Thomas, R. P., Soltys, S. G., Hancock, S. L., Chang, S. D., Reddy, S. A., Gephart, M. H., Li, G. 2020

    Abstract

    Immunotherapy for melanoma patients with brain metastasis has significantly improved outcomes; however, they have also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports suggest these reactions can precede improved treatment responses. We sought to identify if such association exists for intracranial disease control.We conducted a retrospective chart review of melanoma patients who underwent immunotherapy treatment following diagnosis of brain metastasis. The study cohort was then stratified into two groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analysis were used to evaluate survival and predictors of outcomes.Fifty-two patients met inclusion criteria, seventeen of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 vs 10.5 months (p = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival, mean (33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (p = 0.013, HR = 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (p = 0.015, HR = 10.73) CONCLUSION: Immune related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to demonstrate promising outcomes as a first-line agent for melanoma with brain metastasis.

    View details for DOI 10.1016/j.wneu.2020.08.124

    View details for PubMedID 32853767

  • Contralateral acute vascular occlusion following revascularization surgery for moyamoya disease JOURNAL OF NEUROSURGERY Sussman, E. S., Madhugiri, V., Teo, M., Nielsen, T. H., Furtado, S., Pendharkar, A., Ho, A. L., Esparza, R., Azad, T. D., Zhang, M., Steinberg, G. K. 2019; 131 (6): 1702?8

    Abstract

    OBJECTIVERevascularization surgery is a safe and effective surgical treatment for symptomatic moyamoya disease (MMD) and has been shown to reduce the frequency of future ischemic events and improve quality of life in affected patients. The authors sought to investigate the occurrence of acute perioperative occlusion of the contralateral internal carotid artery (ICA) with contralateral stroke following revascularization surgery, a rare complication that has not been previously reported.METHODSThis study is a retrospective review of a prospective database of a single surgeon's series of revascularization operations in patients with MMD. From 1991 to 2016, 1446 bypasses were performed in 905 patients, 89.6% of which involved direct anastomosis of the superficial temporal artery (STA) to a distal branch of the middle cerebral artery (MCA). Demographic, surgical, and radiographic data were collected prospectively in all treated patients.RESULTSSymptomatic contralateral hemispheric infarcts occurred during the postoperative period in 34 cases (2.4%). Digital subtraction angiography (DSA) was performed in each of these patients. In 8 cases (0.6%), DSA during the immediate postoperative period revealed associated new occlusion of the contralateral ICA. In each of these cases, revascularization surgery involved direct anastomosis of the STA to an M4 branch of the MCA. Preoperative DSA revealed moderate (n = 1) or severe (n = 3) stenosis or occlusion (n = 4) of the ipsilateral ICA and mild (n = 2), moderate (n = 4), or severe (n = 2) stenosis of the contralateral ICA. The baseline Suzuki stage was 4 (n = 7) or 5 (n = 1). The collateral supply originated exclusively from the intracranial circulation in 4/8 patients (50%), and from both the intracranial and extracranial circulation in the remaining 50% of patients. Seven (88%) of 8 patients improved symptomatically during the acute postoperative period with induced hypertension. The modified Rankin Scale (mRS) score at discharge was worse than baseline in 7/8 patients (88%), whereas 1 patient had only minor deficits that did not affect the mRS score. At the 3-year follow-up, 3/8 patients (38%) were at their baseline mRS score or better, 1 patient had significant disability compared with preoperatively, 2 patients had died, and 1 patient was lost to follow-up. Three-year follow-up is not yet available in 1 patient.CONCLUSIONSAcute occlusion of the ICA on the contralateral side from an STA-MCA bypass is a rare, but potentially serious, complication of revascularization surgery for MMD. It highlights the importance of the hemodynamic interrelationships that exist between the two hemispheres, a concept that has been previously underappreciated. Induced hypertension during the acute period may provide adequate cerebral blood flow via developing collateral vessels, and good outcomes may be achieved with aggressive supportive management and expedited contralateral revascularization.

    View details for DOI 10.3171/2018.8.JNS18951

    View details for Web of Science ID 000500253800003

    View details for PubMedID 30554188

  • Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Dufort, S., Appelboom, G., Verry, C., Barbier, E. L., Lux, F., Brauer-Krisch, E., Sancey, L., Chang, S. D., Zhang, M., Roux, S., Tillement, O., Le Duc, G. 2019

    Abstract

    We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n?=?7), temozolomide-only (n?=?7), temozolomide and MRT (n?=?9), AGuIX and MRT (n?=?7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n?=?9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1?h after intravenous injection, reaching a mean of 227.9?▒?60?muM. This was compared to concentrations of 10.5?▒?9.2?muM and 62.9?▒?24.7?muM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40?days) compared to the MeST of control rats (25?days) (p?

    View details for DOI 10.1016/j.jocn.2019.05.065

    View details for PubMedID 31281087

  • Microglia are effector cells of CD47-SIRPalpha antiphagocytic axis disruption against glioblastoma. Proceedings of the National Academy of Sciences of the United States of America Hutter, G., Theruvath, J., Graef, C. M., Zhang, M., Schoen, M. K., Manz, E. M., Bennett, M. L., Olson, A., Azad, T. D., Sinha, R., Chan, C., Assad Kahn, S., Gholamin, S., Wilson, C., Grant, G., He, J., Weissman, I. L., Mitra, S. S., Cheshier, S. H. 2019

    Abstract

    Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the tumor microenvironment. Hence, modulation and reeducation of tumor-associated macrophages and microglia in GBM is considered a promising antitumor strategy. Resident microglia and invading macrophages have been shown to have distinct origin and function. Whereas yolk sac-derived microglia reside in the brain, blood-derived monocytes invade the central nervous system only under pathological conditions like tumor formation. We recently showed that disruption of the SIRPalpha-CD47 signaling axis is efficacious against various brain tumors including GBM primarily by inducing tumor phagocytosis. However, most effects are attributed to macrophages recruited from the periphery but the role of the brain resident microglia is unknown. Here, we sought to utilize a model to distinguish resident microglia and peripheral macrophages within the GBM-TAM pool, using orthotopically xenografted, immunodeficient, and syngeneic mouse models with genetically color-coded macrophages (Ccr2 RFP) and microglia (Cx3cr1 GFP). We show that even in the absence of phagocytizing macrophages (Ccr2 RFP/RFP), microglia are effector cells of tumor cell phagocytosis in response to anti-CD47 blockade. Additionally, macrophages and microglia show distinct morphological and transcriptional changes. Importantly, the transcriptional profile of microglia shows less of an inflammatory response which makes them a promising target for clinical applications.

    View details for PubMedID 30602457

  • Outcomes and costs following Ommaya placement with thrombocytopenia among US cancer patients. World neurosurgery Zhang, M., Zhang, Y., Zheng, E., Gephart, M. H., Veeravagu, A., Desai, A., Ratliff, J. K., Li, G. 2019

    Abstract

    Placement of Ommaya reservoirs for administration of intrathecal chemotherapy may be complicated by comorbid thrombocytopenia among patients with hematologic or leptomeningeal disease. Aggregated data on risks of Ommaya placement among thrombocytopenic patients is lacking. This study assesses complications, revision rates, and costs associated with Ommaya placement among patients with thrombocytopenia in a large population sample.Using a national administrative database, this retrospective study identifies a cohort of adult cancer patients who underwent Ommaya placement between 2007 and 2016. Preoperative thrombocytopenia was defined as diagnosis of secondary thrombocytopenia, bleeding event, procedure to control bleeding, or platelet transfusion, within 30 days prior to index admission. Univariate and multivariate analyses were performed to assess costs, 30-day complications, readmissions, and revisions among patients with and without preoperative thrombocytopenia.The analytic cohort included 1652 patients, of whom 29.3% met criteria for preoperative thrombocytopenia. In-hospital mortality rates were 7.7% among thrombocytopenic patients vs. 1.2% among non-thrombocytopenic patients (p < 0.001). Preoperative thrombocytopenia was associated with 14.5 times greater hazard of intracranial hemorrhage within 30 days following Ommaya placement, occurring in 25.6% vs. 2.0% of thrombocytopenic and non-thrombocytopenic patients, respectively (p < 0.014). Revision rates did not differ significantly between thrombocytopenic and non-thrombocytopenic patients. Thrombocytopenia was associated with longer length of stay (7.4 vs 13.9 days, p < 0.001) and additional $10,000 per patient in costs of index hospitalization (p < 0.001).This is the largest study to date documenting costs and complication rates of Ommaya placement in patients with and without thrombocytopenia.

    View details for DOI 10.1016/j.wneu.2019.12.063

    View details for PubMedID 31866457

  • Non-Contrast T2-Weighted MR Sequences for Long Term Monitoring of Asymptomatic Convexity Meningiomas. World neurosurgery He, J. Q., Iv, M., Li, G., Zhang, M., Hayden-Gephart, M. 2019

    Abstract

    Gadolinium based contrast agents (GBCA) used to enhance MRs have been linked to tissue deposition, including in the brain. The management of indolent tumors such as meningiomas requires frequent MRs to monitor for interval growth. Given concern regarding GBCA deposition, we sought to determine if non-contrast MRs in patients with asymptomatic meningiomas were equivalent to GBCA-enhanced MRs in surveillance monitoring.This IRB-approved retrospective chart review included 106 MR sequences from 18 patients. Inclusion criteria were adult patients with asymptomatic meningiomas who received baseline contrast-enhanced and non-contrast axial MR imaging of the brain. Exclusion criteria included: 1) baseline or follow-up axial images were not available for review 2) baseline scan was obtained without contrast 3) diagnosis of meningioma was uncertain. Percent tumor growth was measured by comparing cross-sectional area at maximum tumor diameter from the earliest and most recent scans. For each patient, change in tumor size over time was compared using T1+contrast, T2, and T2 FLAIR sequences. These were compared to a qualitative consensus reading by a neurosurgeon and a neuroradiologist.Measured change of greater than 10% was taken to represent tumor growth. In 17 out of 18 patients, measurement of non-contrast studies (T2 and T2 FLAIR) matched consensus. For one patient, imaging on T2 suggested 11% growth while T2 FLAIR and overall consensus was stability.Our study provides evidence that non-contrasted MR images are equivalent to contrast-weighted MRs to follow change in tumor size over time in asymptomatic meningiomas.

    View details for DOI 10.1016/j.wneu.2019.11.051

    View details for PubMedID 31734418

  • Milestones in stereotactic radiosurgery for the central nervous system. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Mitrasinovic, S., Zhang, M., Appelboom, G., Sussman, E., Moore, J. M., Hancock, S. L., Adler, J. R., Kondziolka, D., Steinberg, G. K., Chang, S. D. 2019; 59: 12?19

    Abstract

    INTRODUCTION: Since Lars Leksell developed the first stereotactic radiosurgery (SRS) device in 1951, there has been growth in the technologies available and clinical indications for SRS. This expansion has been reflected in the medical literature, which is built upon key articles and institutions that have significantly impacted SRS applications. Our aim was to identify these prominent works and provide an educational tool for training and further inquiry.METHOD: A list of search phrases relating to central nervous system applications of stereotactic radiosurgery was compiled. A topic search was performed using PubMed and Scopus databases. The journal, year of publication, authors, treatment technology, clinical subject, study design and level of evidence for each article were documented. Influence was proposed by citation count and rate.RESULTS: Our search identified a total of 10,211 articles with the top 10 publications overall on the study of SRS spanning 443-1313 total citations. Four articles reported on randomized controlled trials, all of which evaluated intracranial metastases. The most prominent subtopics included SRS for arteriovenous malformation, glioblastoma, and acoustic neuroma. Greatest representation by treatment modality included Gamma Knife, LINAC, and TomoTherapy.CONCLUSIONS: This systematic reporting of the influential literature on SRS for intracranial and spinal pathologies underscores the technology's rapid and wide reaching clinical applications. Moreover the findings provide an academic guide to future health practitioners and engineers in their study of SRS for neurosurgery.

    View details for PubMedID 30595165

  • Lumbar Puncture for the Injection of Intrathecal Fluorescein: Should It Be Avoided in a Subset of Patients Undergoing Endoscopic Endonasal Resection of Sellar and Parasellar Lesions? Journal of neurological surgery. Part B, Skull base Zhang, M., Azad, T. D., Singh, H., Salam, S., Jain, S., Anand, V. K., Schwartz, T. H. 2018; 79 (6): 554?58

    Abstract

    Objectives The use of intrathecal fluorescein (ITF) has become an increasingly adopted practice for the identification of cerebrospinal fluid (CSF) leaks during endoscopic skull base surgery for pituitary adenomas. Administration through lumbar puncture can result in postoperative positional headaches, increasing morbidity, cost, and length of stay. We sought to identify the incidence of and variables associated with postoperative headaches to determine if there was a subgroup of patients in whom this procedure should be avoided. Methods We conducted a retrospective single-institution review of 148 patients who underwent endoscopic resection with ITF for pituitary adenoma between December 2003 and February 2016. We excluded patients who had lumbar drains and with intraoperative CSF leak, as these patients may have other headache etiologies. Patient demographics, comorbidities, tumor features, surgical approach, surgical closure, and histology were recorded. Primary outcomes included the presence of postoperative and positional headaches. Results We identified 62 patients with postoperative headaches (41.9%) and 10 with positional headaches (6.8%), of whom 6 underwent blood patch with complete resolution. Following univariate analysis, there was a significant positive association with prolactin-secreting tumors ( p =0.008). There was a negative association with a history of hypertension ( p =0.0001) and age ( p =0.01). Following multivariate modeling, the significance for hypertension ( p =0.01) was preserved. Conclusions Positional headaches in patients who receive ITF are uncommon and should not limit its use in the preparations for endoscopic resection of pituitary adenomas. Avoiding ITF in younger patients without hypertension with prolactinomas might decrease the risk of post-ITF positional headaches.

    View details for DOI 10.1055/s-0038-1635257

    View details for PubMedID 30456024

  • Radiographic Rate and Clinical Impact of Pseudarthrosis in Spine Radiosurgery for Metastatic Spinal Disease. Cureus Zhang, M., Appelboom, G., Ratliff, J. K., Soltys, S. G., Adler, J. R., Park, J., Chang, S. D. 2018; 10 (11): e3631

    Abstract

    Purpose Pseudarthrosis within the spine tumor population is increased from perioperative radiation and complex stabilization for invasive and recurrent pathology. We report the radiographic and clinical rates of pseudarthrosis following multiple courses of instrumented fusion and perioperative stereotactic radiosurgery (SRS). Methods We performed a single institution review of 418 patients treated with non-isocentric SRS for spine between October 2002 and January 2013, identifying those with spinal instrumentation and greater than six months of follow-up. Surgical history, radiation planning, and radiographic outcomes were documented. Results Eleven patients whomet criteria for inclusion underwent 21 sessions of spinal SRS and 16 instrumented operations. Radiographic follow-up was 48.9 months; 3/11 (27%) were with radiographic hardware failure, and one (9%) separate case ultimately warranted externalization due to tumor recurrence. SRS was administered to treat progression of disease in 12/21 (57%) procedures, and residual lesions in 7/11 (64%) procedures. Following first and second SRS, 8/11 (73%) and 2/7 (29%) patients were with symptomatic improvement, respectively. Conclusion Risk of pseudarthrosis following SRS for patients with oncologic spinal lesions will become increasingly apparent with the optimized management of and survival from spinal pathologies. We highlight how the need for local control outpaces the risk of instrumentation failure.

    View details for PubMedID 30705790

  • How Intraoperative Tools and Techniques Have Changed the Approach to Brain Tumor Surgery. Current oncology reports Fatemi, P., Zhang, M., Miller, K. J., Robe, P., Li, G. 2018; 20 (11): 89

    Abstract

    PURPOSE OF REVIEW: Surgical treatment of brain tumors remains an integral part of a comprehensive treatment plan. Here, we review technological advances that have enhanced what surgeons are capable of doing within and outside the traditional operating room.RECENT FINDINGS: Extent of surgical resection has improved with the use of MRI and fluorescent dyes intraoperatively. Neurological injury during brain tumor surgery has decreased with appropriate use of neurophysiological monitoring. New operative scopes have enhanced ability of surgeons to visualize tissues during dissection. Laser interstitial therapy and radiation treatment have made possible the treatment of previously considered non-operable brain tumors in addition to replacing or serving as adjunct to surgical treatment of brain tumors. Surgery remains an important pillar in treatment of most brain tumors. Ongoing technological advances have augmented extent of what is possible in this realm.

    View details for PubMedID 30259202

  • Brainstem Dose Constraints in Nonisometric Radiosurgical Treatment Planning of Trigeminal Neuralgia: A Single-Institution Experience WORLD NEUROSURGERY Zhang, M., Lamsam, L. A., Schoen, M. K., Mehta, S. S., Appelboom, G., Adler, J. K., Soltys, S. G., Chang, S. D. 2018; 113: E399?E407

    Abstract

    CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) administers nonisometric, conformational high-dose radiation to the trigeminal nerve with risk of subsequent hypoesthesia.We performed a retrospective, single-institution review of 66 patients with TGN treated with CyberKnife SRS to compare outcomes from 2 distinct treatment periods: standard dosing (ná= 38) and reduced dosing (ná= 28). Standard and reduced dosing permitted a maximum brainstem dose of 45 Gy and 25 Gy, respectively, each with a prescription dose of 60 Gy. Primary and secondary outcomes were Barrow Neurologic Institute pain and numbness scores. Maximum brainstem dose, prepontine nerve length, and treatment history were recorded for their predictive contributions by logistic regression.After matching, patients in the standard dosing and reduced dosing groups were followed for a median of 25 months and 19.5 months, respectively. Mean trigeminal nerve length was 8.55 mm in the standard dosing group and 9.46 mm in the reduced dosing group. Baseline rates of poorly controlled pain were 97% and 88%, respectively, which improved to 23.4% and 8.3%, respectively (P < 0.001 for both). The baseline rates of bothersome numbness were null in both groups, and increased to 25% in the standard group (Pá= 0.006) and to 21% in the reduced group (Pá= 0.07). Regression analyses suggested that reduced brainstem exposure (Pá= 0.01), as well as a longer trigeminal nerve (Pá= 0.01), were predictive of durable pain control.These outcomes demonstrate that a lower maximum brainstem dose can provide excellent pain control without affecting facial numbness. Longer nerves may achieve better long-term outcomes and help optimize individual plans.

    View details for PubMedID 29454124

  • Long-Term Effectiveness of Gross-Total Resection for Symptomatic Spinal Cord Cavernous Malformations. Neurosurgery Azad, T. D., Veeravagu, A., Li, A., Zhang, M., Madhugiri, V., Steinberg, G. K. 2018

    Abstract

    Intramedullary spinal cord cavernous malformations (CMs) account for 5% of all CMs in the central nervous system and 5% to 12% of all spinal cord vascular lesions, yet their optimal management is controversial.To identify factors associated with the clinical progression of spinal cord CMs and quantify the range of surgical outcomes.Retrospective observational cohort study of 32 patients who underwent open surgical resection for spinal CMs, the majority of which presented to a dorsal or lateral pial surface, from 1996 to 2017 at a single institution. We evaluated outcomes as clinically improved, worsened, or unchanged against preoperative baseline; Frankel and Aminoff-Logue disability grades were also calculated.Mean age at presentation was 44.2 (range, 0.5-77 yr). Symptoms included sensory deficits (n = 26, 81%), loss of strength/coordination (n = 16, 50%), pain (n = 16, 50%), and bladder/bowel dysfunction (n = 6, 19%). Thoracic (n = 16, 50%) and cervical CMs (n = 16, 50%) were equally common, with overall mean size of 7.1 mm (range, 1-20 mm). Functional outcomes at last follow-up, compared to preoperative status for patients with >6 mo of follow-up, were improved in 6 (23%), unchanged in 19 (73%), and worsened in 1 (4%) patients. Preoperative Frankel grade and improved Frankel grade immediately following resection were strongly associated with improvement from baseline at long-term followup (P < .01).Gross total resection of symptomatic spinal cord CMs can prevent further neurological decline. Our experience suggests excellent long-term outcomes and minimal surgical morbidity following resection.

    View details for PubMedID 29425323

  • Management of Arteriovenous Malformations Associated with Developmental Venous Anomalies: A Literature Review and Report of 2 Cases WORLD NEUROSURGERY Zhang, M., Connolly, I. D., Teo, M. K., Yang, G., Dodd, R., Marks, M., Zuccarello, M., Steinberg, G. K. 2017; 106: 563?69

    Abstract

    Classification of cerebrovascular malformations has revealed intermediary lesions that warrant further review owing to their unusual presentation and management. We present 2 cases of arteriovenous malformation (AVM) associated with a developmental venous anomaly (DVA), and discuss the efficacy of previously published management strategies.Two cases of AVMs associated with DVA were identified, and a literature search for published cases between 1980 and 2016 was conducted. Patient demographic data and clinical features were documented.In case 1, a 29-year-old female presenting with parenchymal hemorrhage and left homonymous hemianopia was found to have a right parieto-occipital AVM fed from the anterior cerebral, middle cerebral, and posterior cerebral arteries, with major venous drainage to the superior sagittal sinus. In case 2, imaging in a 34-year-old female evaluated for night tremors and incontinence revealed a left parietal AVM with venous drainage to the superior sagittal sinus. Including our 2 cases, 22 cases of coexisting AVMs and DVAs have been reported in the literature. At presentation, 68% had radiographic evidence of hemorrhage. Stereotactic radiosurgery was performed in 7 cases, embolization in 6 cases, surgical resection in 4 cases, and multimodal therapy in 5 cases. Radiography at follow-up demonstrated successful AVM obliteration in 67% of cases (12 of 18).Patients with coexisting AVMs and DVAs tend to have a hemorrhagic presentation. Contrary to traditional AVM management, in these cases it is important to preserve the draining vein via the DVA to ensure a safe, sustained circulatory outflow of the associated brain parenchyma while achieving safe AVM obliteration.

    View details for PubMedID 28735125

  • Surgeon Procedure Volume and Complication Rates in Anterior Cervical Discectomy and Fusions: Analysis of a National Longitudinal Database. Clinical spine surgery Cole, T., Veeravagu, A., Zhang, M., Ratliff, J. K. 2017; 30 (5): E633-E639

    Abstract

    Retrospective study using the MarketScan longitudinal database (2006-2010).Compare complication rates between groups of patients undergoing anterior cervical discectomy and fusion (ACDF) procedures performed by surgeons with high versus low mean annual ACDF volume.Over the past decade the volume of ACDFs performed has increased, concurrent with greater appreciation of potential for associated complications. The effect of surgeon procedure volume on adverse events occurrence in the postoperative period has not been described.We evaluated the relationship between surgeon procedure volume and postoperative incidence of any complication using a multivariate logistic regression model. A total of 24,461 patients undergoing single and multiple level ACDFs were identified in the MarketScan database by Current Procedural Terminology coding. Annual surgeon volume was determined by tracking of anonymized surgeon identification numbers, with high-volume surgeons defined as those performing an average of at least 30 ACDF procedures annually.Over 50% of unique surgeon identifiers reported <9 ACDF operations per year, whereas the highest decile reported a range of 44-101. High surgeon volume was protective for any complication [odds ratio (OR), 72; 95% confidence interval, 0.65-0.81; P<0.0001], with an adjusted number needed to harm of 44. Patients treated by high-volume physicians specifically had lower odds of dysphagia (2.22% vs. 3.08%; OR, 0.71; P<0.0013), neurological complications (0.33% vs. 0.64%; OR, 0.52; P<0.0107), new diagnosis of chronic pain (0.48% vs. 0.82%; OR, 0.58; P<0.0119), pulmonary complications (1.10% vs. 1.58%; OR, 0.69; P<0.0138), and other wound complications (0.06% vs. 0.22%; OR, 0.28; P<0.0242).We demonstrate a possible association between higher surgeon procedure volume and decreased postoperative complications after ACDF. There was no difference observed in need for revision surgery or readmission rates.

    View details for DOI 10.1097/BSD.0000000000000238

    View details for PubMedID 28525490

  • Surgeon Adherence to Medical Ethics as Contingent on Their Leadership in the Changing Economics of Health Care. World neurosurgery Zhang, M., Volovetz, J., Teo, M. 2017

    View details for DOI 10.1016/j.wneu.2017.04.115

    View details for PubMedID 28456737

  • Disrupting the CD47-SIRP alpha anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors SCIENCE TRANSLATIONAL MEDICINE Gholamin, S., Mitra, S. S., Feroze, A. H., Liu, J., Kahn, S. A., Zhang, M., Esparza, R., Richard, C., Ramaswamy, V., Remke, M., Volkmer, A. K., Willingham, S., Ponnuswami, A., McCarty, A., Lovelace, P., Storm, T. A., Schubert, S., Hutter, G., Narayanan, C., Chu, P., Raabe, E. H., Harsh, G., Taylor, M. D., Monje, M., Cho, Y., Majeti, R., Volkmer, J. P., Fisher, P. G., Grant, G., Steinberg, G. K., Vogel, H., Edwards, M., Weissman, I. L., Cheshier, S. H. 2017; 9 (381)

    Abstract

    Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRP? interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic agent for managing multiple pediatric central nervous system malignancies.

    View details for DOI 10.1126/scitranslmed.aaf2968

    View details for PubMedID 28298418

  • CyberKnife stereotactic radiosurgery for the treatment of symptomatic vertebral hemangiomas: a single-institution experience NEUROSURGICAL FOCUS Zhang, M., Chen, Y., Chang, S. D., Veeravagu, A. 2017; 42 (1)

    Abstract

    OBJECTIVE Symptomatic vertebral hemangiomas (SVHs) are a very rare pathology that can present with persistent pain or neurological deficits that warrant surgical intervention. Given the relative rarity and difficulty in assessment, the authors sought to present a dedicated series of SVHs treated using stereotactic radiosurgery (SRS) to provide insight into clinical decision making. METHODS A retrospective review of a single institution's experience with hypofractionated radiosurgery for SVH from 2004 to 2011 was conducted to determine the clinical and radiographic outcomes following SRS treatment. The authors report and analyze the treatment course of 5 patients with 7 lesions, 2 of which were treated primarily by SRS. RESULTS Of the 5 patients studied, 4 presented with a chief complaint of pain refractory to conservative measures. Three patients reported dysesthesias, and 2 reported upper-extremity weakness. Following radiosurgery, 4 of 5 patients exhibited improvement in their primary symptoms (3 for pain and 1 for weakness), achieving a clinical response after a mean period of 1 year. In 2 cases there was 20%-40% reduction in lesion size in the most responsive dimension as noted on images. All treatments were well tolerated. CONCLUSIONS SRS for SVH is a safe and feasible treatment strategy, comparable to prior radiotherapy studies, and in select cases may successfully confer delayed decompressive effects. Additional investigation will determine future patient selection and how conformal SRS treatment can best be administered.

    View details for DOI 10.3171/2016.9.FOCUS16372

    View details for Web of Science ID 000392113200013

    View details for PubMedID 28041316

  • Clinical and Arterial Spin Labeling Brain MRI Features of Transitional Venous Anomalies. Journal of neuroimaging : official journal of the American Society of Neuroimaging Zhang, M., Telischak, N. A., Fischbein, N. J., Steinberg, G. K., Marks, M., Zaharchuk, G., Heit, J. J., Iv, M. 2017

    Abstract

    Transitional venous anomalies (TVAs) are rare cerebrovascular lesions that resemble developmental venous anomalies (DVAs), but demonstrate early arteriovenous shunting on digital subtraction angiography (DSA) without the parenchymal nidus of arteriovenous malformations (AVMs). We investigate whether arterial spin labeling (ASL) magnetic resonance imaging (MRI) can distinguish brain TVAs from DVAs and guide their clinical management.We conducted a single-center retrospective review of patients with brain parenchymal DVA-like lesions with increased ASL signal on MRI. Clinical histories and follow-up information were obtained. Two readers assessed ASL signal location relative to the vascular lesion on MRI and, if available, the presence of arteriovenous shunting on DSA.Thirty patients with DVA-like lesions with increased ASL signal were identified. Clinical symptoms prompted MRI evaluation in 83%. Symptoms did not localize to the venous anomaly in 90%. Ten percent presented with acute symptoms, only one of whom presented with hemorrhage. ASL signal in relation to the venous anomaly was identified in: 50% in the adjacent parenchyma, 33% in the lesion, 7% in a distal draining vein/sinus, and 10% in at least two of these sites. Follow-up DSA confirmed arteriovenous shunting in 71% of ASL-positive venous anomalies. Interrater agreement was very good (? = .81-1.0, P < .001).A DVA-like lesion with increased ASL signal likely represents a TVA with arteriovenous shunting. Our study indicates that these lesions are usually incidentally detected and have a lower risk of hemorrhage than AVMs. ASL-MRI may be a useful tool to identify TVAs and guide further management of patients with TVAs.

    View details for PubMedID 29205641

  • Implications of Antiangiogenic Therapy on Radiographic Assessment of Brain Tumors. World neurosurgery Narayanamurthy, H., Zhang, M., Teo, M. 2017; 108: 380?82

    View details for PubMedID 28919561

  • Outcomes of cervical laminoplasty-Population-level analysis of a national longitudinal database. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Veeravagu, A., Azad, T. D., Zhang, M., Li, A., Pendharkar, A. V., Ratliff, J. K., Shuer, L. M. 2017

    Abstract

    Cervical laminoplasty is an important alternative to laminectomy in decompressing of the cervical spine. Further evidence to assess the utility of laminoplasty is required. We examine outcomes of cervical laminoplasty via a population level analysis in the United States.We performed a population-level analysis using the national MarketScan longitudinal database to analyze outcomes and costs of cervical laminoplasty between 2007 and 2014. Outcomes included postoperative complications, revision rates, and functional outcomes.Using a national administrative database, we identified 2613 patients (65.6% male, mean 58.5?years) who underwent cervical laminoplasty. Mean length of stay was 3.1?▒?2.8?days and mean follow-up was 795.5?▒?670.6?days. The overall complication rate was 22.5% (N?=?587), 30-day readmission rate was 7.5% (N?=?195), and mortality rate was 0.08% (N?=?2, elderly patients only). The complication rate was significantly increased in elderly patients (age >65?years) compared to non-elderly patients (OR 0.751, p?

    View details for PubMedID 29153782

  • The Outcome of Hypofractionated Stereotactic Radiosurgery for Large Vestibular Schwannomas. World neurosurgery Teo, M., Zhang, M., Li, A., Thompson, P. A., Tayag, A. T., Wallach, J., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Chang, S. D. 2016; 93: 398-409

    Abstract

    Stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS) remains controversial. We studied the tumor local control and toxicity rates after hypofractionated SRS for VS > 3 cm.A total of 587 patients with VS treated with SRS between 1998 and 2014 were reviewed retrospectively, and 30 Koos grade IV VSs were identified. There were 6 patients with neurofibromatosis 2 (NF2), 8 with cystic tumors, 22 with solid tumors, 19 who underwent primary CyberKnife (CK), and 11 with >3 cm after previous resection. Patients were treated by a median of 3 fractions at 18 Gy.After a median 97 months, the 3- and 10-year Kaplan-Meier estimates of local control were 85% and 80%, respectively, with 20% requiring salvage treatment. For patients who had previous tumor resection rather than primary CK, the estimates were 46% and 5%, respectively, with progression, and 3-year control rates of 71% and 94% (Pá= 0.008). Tumor control was also lower among NF2 versus non-NF2 patients (40% vs. 95%; Pá= 0.0014). Among patients with good clinical baselines before CK, 88% were functionally independent (modified Rankin Scale score, 0-2), 88% had good facial function (House-Brackmann grade I-II), and 38% had serviceable hearing (Gardner-Robertson grade I-II) at last follow-up. Hearing worsening was more likely among patients treated with primary CK (33% vs. 90%; Pá= 0.04).Overall, 80% of large VSs were adequately controlled by CK with 97 months of median follow-up. Patients with previous surgery and NF2 also appeared to have higher rates of tumor progression, and less favorable functional outcomes.

    View details for DOI 10.1016/j.wneu.2016.06.080

    View details for PubMedID 27368508

  • Required Reading: The Most Impactful Articles in Endoscopic Endonasal Skull Base Surgery. World neurosurgery Zhang, M., Singh, H., Almodovar-Mercado, G. J., Anand, V. K., Schwartz, T. H. 2016; 92: 499-512 e2

    Abstract

    Endoscopic endonasal skull base surgery has become a widely accepted field in neurosurgery and otolaryngology over the last 15 years. However, there has yet to be a formal curation of the most impactful articles for an introductory curriculum to its technical evolution.The Science Citation Index Expanded was used to generate a citation rank list (October 2015) on articles relevant to endoscopic skull base surgery. The top 35 cited articles overall, as well as the top 15 since 2009, were identified. Journal, year, author, study population, article format, and level of evidence were compiled. Additional surgeon-experts were polled and made recommendations for significant contributions to the literature.The top 35 publications ranged from 98 to 467 citations and were published in 10 different journals. Four articles had over 250 citations. A period of frequent contribution occurred between 2005-2009, when 21/35 reports were published. 18/35 articles were case series, and 13/35 were technical reports. There were 11/35 articles focused primarily on pituitary surgery, and 10/35 on extra-sellar lesions. The top 15 articles since 2009 had 8/15 articles focus on extra-sellar lesions. Polled surgeons consistently identified the most prominently cited articles, and their recommendations drew attention to CSF-leak as well as extra-sellar management.Identification of the most cited works within endoscopic endonasal skull base surgery demonstrates greater anatomical access and safety over the last two decades. These articles can serve as an educational tool for novices or mid-level practitioners wishing to obtain a greater understanding of the field.

    View details for DOI 10.1016/j.wneu.2016.06.016

    View details for PubMedID 27312387

  • CyberKnife Stereotactic Radiosurgery for Atypical and Malignant Meningiomas. World neurosurgery Zhang, M., Ho, A. L., D'Astous, M., Pendharkar, A. V., Choi, C. Y., Thompson, P. A., Tayag, A. T., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2016; 91: 574-581 e1

    Abstract

    Recurrent World Health Organization (WHO) grade II and III meningiomas have traditionally been treated by surgery alone, but early literature suggests that adjuvant stereotactic radiosurgery may greatly improve outcomes. We present the long-term tumor control and safety of a hypofractionated stereotactic radiosurgery regimen.Prospectively collected data of 44 WHO grade II and 9 WHO grade III meningiomas treated by CyberKnife for adjuvant or salvage therapy were reviewed. Patient demographics, treatment parameters, local control, regional control, locoregional control, overall survival, radiation history, and complications were documented.For WHO grade II patients, recurrence occurred in 41%, with local, regional, and locoregional failure at 60 months recorded as 49%, 58%, and 36%. For WHO grade III patients, recurrence occurred in 66%, with local, regional, and locoregional failure at 12 months recorded as 57%, 100%, and 43%. The 60-month locoregional control rates for radiation na´ve and experienced patients were 48% and 0% (Pá=á0.14). Overall, 7 of 44 grade II patients and 8 of 9 grade III patients had died at last follow-up. The 60-month and 12-month overall survival rates for grade II and III meningiomas were 87% and 50%, respectively. Serious complications occurred in 7.5% of patients.Stereotactic radiosurgery for adjuvant and salvage treatment of WHO grade II meningioma using a hypofractionated plan is a viable treatment strategy with acceptable long-term tumor control, overall survival, and complication rates. Future studies should focus on radiation-na´ve patients and local management of malignant meningioma.

    View details for DOI 10.1016/j.wneu.2016.04.019

    View details for PubMedID 27108030

  • Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo PLOS ONE Zhang, M., Hutter, G., Kahn, S. A., Azad, T. D., Gholamin, S., Xu, C. Y., Liu, J., Achrol, A. S., Richard, C., Sommerkamp, P., Schoen, M. K., McCracken, M. N., Majeti, R., Weissman, I., Mitra, S. S., Cheshier, S. H. 2016; 11 (4)

    Abstract

    Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo.

    View details for DOI 10.1371/journal.pone.0153550

    View details for Web of Science ID 000374541200027

    View details for PubMedID 27092773

    View details for PubMedCentralID PMC4836698

  • Intracranial Dislocation of the Mandibular Condyle: A Case Report and Literature Review WORLD NEUROSURGERY Zhang, M., Alexander, A. L., Most, S. P., Li, G., Harris, O. A. 2016; 86

    View details for DOI 10.1016/j.wneu.2015.09.007

    View details for PubMedID 26365884

  • Neural Placode Tissue Derived From Myelomeningocele Repair Serves as a Viable Source of Oligodendrocyte Progenitor Cells. Neurosurgery Mitra, S. S., Feroze, A. H., Gholamin, S., Richard, C., Esparza, R., Zhang, M., Azad, T. D., Alrfaei, B., Kahn, S. A., Hutter, G., Guzman, R., Creasey, G. H., Plant, G. W., Weissman, I. L., Edwards, M. S., Cheshier, S. 2015; 77 (5): 794-802

    Abstract

    The presence, characteristics, and potential clinical relevance of neural progenitor populations within the neural placodes of myelomeningocele patients remain to be studied. Neural stem cells are known to reside adjacent to ependyma-lined surfaces along the central nervous system axis.Given such neuroanatomic correlation and regenerative capacity in fetal development, we assessed myelomeningocele-derived neural placode tissue as a potentially novel source of neural stem and progenitor cells.Nonfunctional neural placode tissue was harvested from infants during the surgical repair of myelomeningocele and subsequently further analyzed by in vitro studies, flow cytometry, and immunofluorescence. To assess lineage potential, neural placode-derived neurospheres were subjected to differential media conditions. Through assessment of platelet-derived growth factor receptor ? (PDGFR?) and CD15 cell marker expression, Sox2+Olig2+ putative oligodendrocyte progenitor cells were successfully isolated.PDGFR?CD15 cell populations demonstrated the highest rate of self-renewal capacity and multipotency of cell progeny. Immunofluorescence of neural placode-derived neurospheres demonstrated preferential expression of the oligodendrocyte progenitor marker, CNPase, whereas differentiation to neurons and astrocytes was also noted, albeit to a limited degree.Neural placode tissue contains multipotent progenitors that are preferentially biased toward oligodendrocyte progenitor cell differentiation and presents a novel source of such cells for use in the treatment of a variety of pediatric and adult neurological disease, including spinal cord injury, multiple sclerosis, and metabolic leukoencephalopathies.

    View details for DOI 10.1227/NEU.0000000000000918

    View details for PubMedID 26225855

  • Anterior Versus Posterior Approach for Multilevel Degenerative Cervical Disease A Retrospective Propensity Score-Matched Study of the MarketScan Database SPINE Cole, T., Veeravagu, A., Zhang, M., Azad, T. D., Desai, A., Ratliff, J. K. 2015; 40 (13): 1033-1038

    Abstract

    Retrospective 2:1 propensity score-matched analysis on a national longitudinal database between 2006 and 2010.To compare rates of adverse events, revisions procedure rates, and payment differences in anterior cervical fusion procedures compared with posterior laminectomy and fusion procedures with at least 3 levels of instrumentation.The comparative benefits of anterior versus posterior approach to multilevel degenerative cervical disease remain controversial. Recent systematic reviews have reached conflicting conclusions. We demonstrate the comparative economic and clinical outcomes of anterior and posterior approaches for multilevel cervical degenerative disk disease.We identified 13,662 patients in a national billing claims database who underwent anterior or posterior cervical fusion procedures with 3 or more levels of instrumentation. Cohorts were balanced using 2:1 propensity score matching and outcomes were compared using bivariate analysis.With the exception of dysphagia (6.4% in anterior and 1.4% in posterior), overall 30-day complication rates were lower in the anterior approach group. The rate of any complication excluding dysphagia with anterior approaches was 12.3%, significantly lower (P < 0.0001) than that of posterior approaches, 17.8%. Anterior approaches resulted in lower hospital ($18,346 vs. $23,638) and total payments ($28,963 vs. $33,526). Patients receiving an anterior surgical approach demonstrated significantly lower rate of 30-day readmission (5.1% vs. 9.9%, P < 0.0001), were less likely to require revision surgery (12.8% vs. 18.1%, P < 0.0001), and had a shorter length of stay by 1.5 nights (P < 0.0001).Anterior approaches in the surgical management of multilevel degenerative cervical disease provide clinical advantages over posterior approaches, including lower overall complication rates, revision procedure rates, and decreased length of stay. Anterior approach procedures are also associated with decreased overall payments. These findings must be interpreted in light of limitations inherent to retrospective longitudinal studies including absence of subjective and radiographical outcomes.3.

    View details for DOI 10.1097/BRS.0000000000000872

    View details for Web of Science ID 000357946000009

  • Anterior Versus Posterior Approach for Multilevel Degenerative Cervical Disease: A Retrospective Propensity Score-Matched Study of the MarketScan Database. Spine Cole, T., Veeravagu, A., Zhang, M., Azad, T. D., Desai, A., Ratliff, J. K. 2015; 40 (13): 1033-1038

    Abstract

    Retrospective 2:1 propensity score-matched analysis on a national longitudinal database between 2006 and 2010.To compare rates of adverse events, revisions procedure rates, and payment differences in anterior cervical fusion procedures compared with posterior laminectomy and fusion procedures with at least 3 levels of instrumentation.The comparative benefits of anterior versus posterior approach to multilevel degenerative cervical disease remain controversial. Recent systematic reviews have reached conflicting conclusions. We demonstrate the comparative economic and clinical outcomes of anterior and posterior approaches for multilevel cervical degenerative disk disease.We identified 13,662 patients in a national billing claims database who underwent anterior or posterior cervical fusion procedures with 3 or more levels of instrumentation. Cohorts were balanced using 2:1 propensity score matching and outcomes were compared using bivariate analysis.With the exception of dysphagia (6.4% in anterior and 1.4% in posterior), overall 30-day complication rates were lower in the anterior approach group. The rate of any complication excluding dysphagia with anterior approaches was 12.3%, significantly lower (P < 0.0001) than that of posterior approaches, 17.8%. Anterior approaches resulted in lower hospital ($18,346 vs. $23,638) and total payments ($28,963 vs. $33,526). Patients receiving an anterior surgical approach demonstrated significantly lower rate of 30-day readmission (5.1% vs. 9.9%, P < 0.0001), were less likely to require revision surgery (12.8% vs. 18.1%, P < 0.0001), and had a shorter length of stay by 1.5 nights (P < 0.0001).Anterior approaches in the surgical management of multilevel degenerative cervical disease provide clinical advantages over posterior approaches, including lower overall complication rates, revision procedure rates, and decreased length of stay. Anterior approach procedures are also associated with decreased overall payments. These findings must be interpreted in light of limitations inherent to retrospective longitudinal studies including absence of subjective and radiographical outcomes.3.

    View details for DOI 10.1097/BRS.0000000000000872

    View details for PubMedID 25768690

  • Deep Brain Stimulation for Obesity. Cureus Ho, A. L., Sussman, E. S., Zhang, M., Pendharkar, A. V., Azagury, D. E., Bohon, C., Halpern, C. H. 2015; 7 (3)

    Abstract

    Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer's disease, and depression and obsessive-compulsive disorderáhave demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain.

    View details for DOI 10.7759/cureus.259

    View details for PubMedID 26180683

  • Macrophages eat cancer cells using their own calreticulin as a guide: Roles of TLR and Btk. Proceedings of the National Academy of Sciences of the United States of America Feng, M., Chen, J. Y., Weissman-Tsukamoto, R., Volkmer, J., Ho, P. Y., McKenna, K. M., Cheshier, S., Zhang, M., Guo, N., Gip, P., Mitra, S. S., Weissman, I. L. 2015; 112 (7): 2145-2150

    Abstract

    Macrophage-mediated programmed cell removal (PrCR) is an important mechanism of eliminating diseased and damaged cells before programmed cell death. The induction of PrCR by eat-me signals on tumor cells is countered by don't-eat-me signals such as CD47, which binds macrophage signal-regulatory protein ? to inhibit phagocytosis. Blockade of CD47 on tumor cells leads to phagocytosis by macrophages. Here we demonstrate that the activation of Toll-like receptor (TLR) signaling pathways in macrophages synergizes with blocking CD47 on tumor cells to enhance PrCR. Bruton's tyrosine kinase (Btk) mediates TLR signaling in macrophages. Calreticulin, previously shown to be an eat-me signal on cancer cells, is activated in macrophages for secretion and cell-surface exposure by TLR and Btk to target cancer cells for phagocytosis, even if the cancer cells themselves do not express calreticulin.

    View details for DOI 10.1073/pnas.1424907112

    View details for PubMedID 25646432

  • Retrosigmoid Versus Translabyrinthine Approach for Acoustic Neuroma Resection: An Assessment of Complications and Payments in a Longitudinal Administrative Database. Cure»us Cole, T., Veeravagu, A., Zhang, M., Azad, T., Swinney, C., Li, G. H., Ratliff, J. K., Giannotta, S. L. 2015; 7 (10)

    Abstract

    Object Retrosigmoid (RS) and translabyrinthine (TL) surgery remain essential treatment approaches for symptomatic or enlarging acoustic neuromas (ANs). We compared nationwide complication rates and payments, independent of tumor characteristics, for these two strategies. Methods We identified 346 and 130 patients who underwent RS and TL approaches, respectively, for AN resection in the 2010-2012 MarketScan database, which characterizes primarily privately-insured patients from multiple institutions nationwide. Results Although we found no difference in 30-day general neurological or neurosurgical complication rates, in TL procedures there was a decreased risk for postoperative cranial nerve (CN) VII injury (20.2% vs 10.0%, CI 0.23-0.82), dysphagia (10.4% vs 3.1%, CI 0.10-0.78), and dysrhythmia (8.4% vs 2.3%, CI 0.08-0.86). Overall, there was no difference in surgical repair rates of CSF leak; however, intraoperative fat grafting was significantly higher in TL approaches (19.8% vs 60.2%, CI 3.95-9.43). In patients receiving grafts, there was a trend towards a higher repair rate after RS approach, while in those without grafts, there was a trend towards a higher repair rate after TL approach. Median total payments were $16,856 higher after RS approaches ($67,774 vs $50,918, p < 0.0001), without differences in physician or 90-day postoperative payments. Conclusionsá Using a nationwide longitudinal database, we observed that the TL, compared to RS, approach for AN resection experienced lower risks of CN VII injury, dysphagia, and dysrhythmia. There was no significant difference in CSF leak repair rates. The payments for RS procedures exceed payments for TL procedures by approximately $17,000. Data from additional years and non-private sources will further clarify these trends.

    View details for DOI 10.7759/cureus.369

    View details for PubMedID 26623224

    View details for PubMedCentralID PMC4659577

  • Galvanizing medical students in the administration of influenza vaccines: the Stanford Flu Crew. Advances in medical education and practice Rizal, R. E., Mediratta, R. P., Xie, J., Kambhampati, S., Hills-Evans, K., Montacute, T., Zhang, M., Zaw, C., He, J., Sanchez, M., Pischel, L. 2015; 6: 471-477

    Abstract

    Many national organizations call for medical students to receive more public health education in medical school. Nonetheless, limited evidence exists about successful servicelearning programs that administer preventive health services in nonclinical settings. The Flu Crew program, started in 2001 at the Stanford University School of Medicine, provides preclinical medical students with opportunities to administer influenza immunizations in the local community. Medical students consider Flu Crew to be an important part of their medical education that cannot be learned in the classroom. Through delivering vaccines to where people live, eat, work, and pray, Flu Crew teaches medical students about patient care, preventive medicine, and population health needs. Additionally, Flu Crew allows students to work with several partners in the community in order to understand how various stakeholders improve the delivery of population health services. Flu Crew teaches students how to address common vaccination myths and provides insights into implementing public health interventions. This article describes the Stanford Flu Crew curriculum, outlines the planning needed to organize immunization events, shares findings from medical students' attitudes about population health, highlights the program's outcomes, and summarizes the lessons learned. This article suggests that Flu Crew is an example of one viable service-learning modality that supports influenza vaccinations in nonclinical settings while simultaneously benefiting future clinicians.

    View details for DOI 10.2147/AMEP.S70294

    View details for PubMedID 26170731

    View details for PubMedCentralID PMC4492543

  • Intraoperative Neuromonitoring in Single-Level Spinal Procedures A Retrospective Propensity Score-Matched Analysis in a National Longitudinal Database SPINE Cole, T., Veeravagu, A., Zhang, M., Li, A., Ratliff, J. K. 2014; 39 (23): 1950-1959

    Abstract

    Study Design. Retrospective propensity score-matched analysis on a national database (MarketScan) between 2006 and 2010.Objective. To compare rates of neurological deficits after elective single level spinal procedures with and without intraoperative neuromonitoring, as well as associated payment differences and geographic variance.Summary of Background Data. Intraoperative neurophysiologic monitoring is a technique that may contribute to avoiding permanent neurological injury during some spine surgery procedures. However, it is unclear if all patients undergoing spine surgery benefit from neuromonitoring.Methods. An identified 85,640 patients underwent single level spinal procedures including anterior cervical discectomy and fusion (ACDF), lumbar fusion, lumbar laminectomy, or lumbar discectomy. Neuromonitoring was identified with appropriate Current Procedural Terminology (CPT) codes. Cohorts were balanced on baseline comorbidities and procedure characteristics using propensity score matching. Trauma and spinal tumors cases were excluded.Results. 12.66% patients received neuromonitoring intraoperatively. Lumbar laminectomies had reduced 30-day neurological complication rate with neuromonitoring (0.0% vs 1.18%, p = 0.002). Neuromonitoring did not correlate with reduced intraoperative neurological complications in ACDFs (0.09% vs 0.13%), lumbar fusions (0.32% vs 0.58%), or lumbar discectomy (1.24% vs. 0.91%). With the addition of neuromonitoring, payments for ACDFs increased 16.24% ($3,842), lumbar fusions 7.84% ($3,540), lumbar laminectomies 24.33% ($3,704), and lumbar discectomies 22.54% ($2.859). Significant geographic variation was evident. Some states had no recorded single-level spinal cases with concurrent neuromonitoring. Rates for ACDFs and lumbar fusions, laminectomies, and discectomies ranged as high as 61%, 58%, 22%, and 21%, respectively.Conclusions. With intraoperative neurological monitoring in single level procedures, neurological complications were only decreased among lumbar laminectomies. No difference was observed in ACDFs, lumbar fusions, or lumbar discectomies. There was a significant increase in total payments associated with the index procedure and hospitalization. We demonstrate significant geographic variation in neuromonitoring.

    View details for DOI 10.1097/BRS.0000000000000593

    View details for Web of Science ID 000344606100014

  • Intraoperative neuromonitoring in single-level spinal procedures: a retrospective propensity score-matched analysis in a national longitudinal database. Spine Cole, T., Veeravagu, A., Zhang, M., Li, A., Ratliff, J. K. 2014; 39 (23): 1950-1959

    Abstract

    Study Design. Retrospective propensity score-matched analysis on a national database (MarketScan) between 2006 and 2010.Objective. To compare rates of neurological deficits after elective single level spinal procedures with and without intraoperative neuromonitoring, as well as associated payment differences and geographic variance.Summary of Background Data. Intraoperative neurophysiologic monitoring is a technique that may contribute to avoiding permanent neurological injury during some spine surgery procedures. However, it is unclear if all patients undergoing spine surgery benefit from neuromonitoring.Methods. An identified 85,640 patients underwent single level spinal procedures including anterior cervical discectomy and fusion (ACDF), lumbar fusion, lumbar laminectomy, or lumbar discectomy. Neuromonitoring was identified with appropriate Current Procedural Terminology (CPT) codes. Cohorts were balanced on baseline comorbidities and procedure characteristics using propensity score matching. Trauma and spinal tumors cases were excluded.Results. 12.66% patients received neuromonitoring intraoperatively. Lumbar laminectomies had reduced 30-day neurological complication rate with neuromonitoring (0.0% vs 1.18%, p = 0.002). Neuromonitoring did not correlate with reduced intraoperative neurological complications in ACDFs (0.09% vs 0.13%), lumbar fusions (0.32% vs 0.58%), or lumbar discectomy (1.24% vs. 0.91%). With the addition of neuromonitoring, payments for ACDFs increased 16.24% ($3,842), lumbar fusions 7.84% ($3,540), lumbar laminectomies 24.33% ($3,704), and lumbar discectomies 22.54% ($2.859). Significant geographic variation was evident. Some states had no recorded single-level spinal cases with concurrent neuromonitoring. Rates for ACDFs and lumbar fusions, laminectomies, and discectomies ranged as high as 61%, 58%, 22%, and 21%, respectively.Conclusions. With intraoperative neurological monitoring in single level procedures, neurological complications were only decreased among lumbar laminectomies. No difference was observed in ACDFs, lumbar fusions, or lumbar discectomies. There was a significant increase in total payments associated with the index procedure and hospitalization. We demonstrate significant geographic variation in neuromonitoring.

    View details for DOI 10.1097/BRS.0000000000000593

    View details for PubMedID 25202940

  • Outcomes following malignant degeneration of benign vestibular schwannomas after stereotactic radiosurgery. World neurosurgery Zhang, M., Chang, S. D. 2014; 82 (3-4): 346-349

    View details for DOI 10.1016/j.wneu.2014.03.005

    View details for PubMedID 24613663

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