All Publications

  • 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


    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

  • 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


    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 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)


    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

  • 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


    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

  • 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


    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

  • 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)


    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

  • 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


    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


    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


    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)


    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


    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


    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

  • 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)


    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


    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)


    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


    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


    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

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