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Anna Tietze, Changho Choi, Bruce Mickey, Elizabeth A Maher, Benedicte Parm Ulhøi, Ryan Sangill, Yasmin Lassen-Ramshad, Slavka Lukacova, Leif Østergaard, Gorm von Oettingen
OBJECTIVE Mutations in the isocitrate dehydrogenase (IDH) genes are of proven diagnostic and prognostic significance for cerebral gliomas. The objective of this study was to evaluate the clinical feasibility of using a recently described method for determining IDH mutation status by using magnetic resonance spectroscopy (MRS) to detect the presence of 2-hydroxyglutarate (2HG), the metabolic product of the mutant IDH enzyme. METHODS By extending imaging time by 6 minutes, the authors were able to include a point-resolved spectroscopy (PRESS) MRS sequence in their routine glioma imaging protocol...
March 3, 2017: Journal of Neurosurgery
Changho Choi, Jack M Raisanen, Sandeep K Ganji, Song Zhang, Sarah S McNeil, Zhongxu An, Akshay Madan, Kimmo J Hatanpaa, Vamsidhara Vemireddy, Christie A Sheppard, Dwight Oliver, Keith M Hulsey, Vivek Tiwari, Tomoyuki Mashimo, James Battiste, Samuel Barnett, Christopher J Madden, Toral R Patel, Edward Pan, Craig R Malloy, Bruce E Mickey, Robert M Bachoo, Elizabeth A Maher
Purpose Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase ( IDH). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging biomarker for IDH-mutated gliomas. Patients and Methods 2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment...
November 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Dinesh K Singh, Rahul K Kollipara, Vamsidara Vemireddy, Xiao-Li Yang, Yuxiao Sun, Nanda Regmi, Stefan Klingler, Kimmo J Hatanpaa, Jack Raisanen, Steve K Cho, Shyam Sirasanagandla, Suraj Nannepaga, Sara Piccirillo, Tomoyuki Mashimo, Shan Wang, Caroline G Humphries, Bruce Mickey, Elizabeth A Maher, Hongwu Zheng, Ryung S Kim, Ralf Kittler, Robert M Bachoo
Efforts to identify and target glioblastoma (GBM) drivers have primarily focused on receptor tyrosine kinases (RTKs). Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2) and zinc-finger E-box binding homeobox 1 (ZEB1), which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets...
January 24, 2017: Cell Reports
Zhongxu An, Sandeep K Ganji, Vivek Tiwari, Marco C Pinho, Toral Patel, Samuel Barnett, Edward Pan, Bruce E Mickey, Elizabeth A Maher, Changho Choi
PURPOSE: To test the efficacy of triple-refocusing MR spectroscopy (MRS) for improved detection of 2-hydroxyglutarate (2HG) in brain tumors at 3T in vivo. METHODS: The triple-refocusing sequence parameters were tailored at 3T, with density-matrix simulations and phantom validation, for enhancing the 2HG 2.25-ppm signal selectivity with respect to the adjacent resonances of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA). In vivo MRS data were acquired from 15 glioma patients and analyzed with LCModel using calculated basis spectra...
July 25, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Hai Chen, Pradeep N Modur, Niravkumar Barot, Paul C Van Ness, Mark A Agostini, Kan Ding, Puneet Gupta, Ryan Hays, Bruce Mickey
Objective. We investigated the longitudinal outcome of resective epilepsy surgery to identify the predictors of seizure recurrence. Materials and Methods. We retrospectively analyzed patients who underwent resections for intractable epilepsy over a period of 7 years. Multiple variables were investigated as potential predictors of seizure recurrence. The time to first postoperative seizure was evaluated using survival analysis and univariate analysis at annual intervals. Results. Among 70 patients, 54 (77%) had temporal and 16 (23%) had extratemporal resections...
2016: Epilepsy Research and Treatment
Kumar Pichumani, Tomoyuki Mashimo, Vamsidhara Vemireddy, Zoltan Kovacs, James Ratnakar, Bruce Mickey, Craig R Malloy, Ralph J DeBerardinis, Robert M Bachoo, Elizabeth A Maher
(13)C-enriched compounds are readily metabolized in human malignancies. Fragments of the tumor, acquired by biopsy or surgical resection, may be acid-extracted and (13)C NMR spectroscopy of metabolites such as glutamate, glutamine, 2-hydroxyglutarate, lactate and others provide a rich source of information about tumor metabolism in situ. Recently we observed (13)C-(13)C spin-spin coupling in (13)C NMR spectra of lactate in brain tumors removed from patients who were infused with [1,2-(13)C]acetate prior to the surgery...
July 2016: Neurochemistry International
Sandeep K Ganji, Zhongxu An, Vivek Tiwari, Sarah McNeil, Marco C Pinho, Edward Pan, Bruce E Mickey, Elizabeth A Maher, Changho Choi
PURPOSE: To test the efficacy of 7T MRS for in vivo detection of 2-hydroxyglutarate (2HG) in brain tumors. METHODS: The subecho times of point-resolved spectroscopy (PRESS) were optimized at 7T with density-matrix simulations and phantom validation to improve the 2HG signal selectivity with respect to the neighboring resonances of γ-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln). MRS data were acquired from 12 subjects with gliomas in vivo and analyzed with LCModel using calculated basis spectra...
March 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Zabi Wardak, Alexander Augustyn, Hong Zhu, Bruce E Mickey, Louis A Whitworth, Christopher J Madden, Samuel L Barnett, Ramzi E Abdulrahman, Lucien A Nedzi, Robert D Timmerman, Kevin S Choe
The number of brain metastases identified on diagnostic magnetic resonance imaging (MRI) is a key factor in consideration of stereotactic radiosurgery (SRS). However, additional lesions are often detected on high-resolution SRS-planning MRI. We investigated pre-treatment clinical characteristics that are associated with finding additional metastases at SRS. Patients treated with SRS for brain metastases between the years of 2009-2014 comprised the study cohort. All patients underwent frame-fixed, 1 mm thick MRI on the day of SRS...
June 2016: Journal of Neuro-oncology
Shai M Rozen, Bridget L Harrison, Brandon Isaacson, J Walter Kutz, Peter S Roland, Patricia A Blau, Samuel L Barnett, Bruce E Mickey
BACKGROUND: Reconstructive surgeons may encounter patients presenting after intracranial facial nerve resection and grafting in the setting of skull base tumors, who inquire regarding progression, final facial function, and need for future operations. Study goals were to analyze global and regional facial function using established grading systems and videography, while examine variables possibly affecting outcomes. METHODS: Between 1997 and 2012, 28 patients underwent intracranial nerve grafting...
January 2016: Plastic and Reconstructive Surgery
Timothy E Richardson, Derek A Mathis, Bruce E Mickey, Jack M Raisanen, Dennis K Burns, Charles L White, Kimmo J Hatanpaa
Silent subtype III pituitary adenomas (SS-3) are nonfunctioning radiosensitive adenomas that may be associated with an increased risk of recurrence and invasion. The features that have been proposed to be diagnostically important are identifiable by electron microscopy (EM) and include an enlarged Golgi apparatus, along with several other ultrastructural features. The often limited availability of EM and the uncertainty about the relative importance of individual features pose practical challenges to the diagnosis...
December 2015: Journal of Neuropathology and Experimental Neurology
Elvis Camacho, Melissa A LoPresti, Sam Bruce, Derek Lin, Mickey Abraham, Geoff Appelboom, Blake Taylor, Michael McDowell, Byron DuBois, Mihika Sathe, E Sander Connolly
We aimed to identify the role of age in intracerebral hemorrhage (ICH), as well as characterize the most commonly used age cut off points in the literature, with the hope of understanding and guiding treatment. Strokes are one of the leading causes of death in the USA, and ICH is the deadliest type. Age is a strong risk factor, but it also affects the body in numerous ways, including changes to the cardiovascular and central nervous systems that interplay with the multiple risk factors for ICH. Understanding the role of age in risk and outcomes of ICH can guide treatment and future clinical trials...
December 2015: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Melanie M Taylor, Daniel R Newman, Julia A Schillinger, Felicia M T Lewis, Bruce Furness, Sarah Braunstein, Tom Mickey, Julia Skinner, Michael Eberhart, Jenevieve Opoku, Susan Blank, Thomas A Peterman
BACKGROUND: Incident syphilis among HIV-infected persons indicates the ongoing behavioral risk for HIV transmission. Detectable viral loads (VLs) among coinfected cases may amplify this risk. METHODS: Primary and secondary cases reported during 2009-2010 from 4 US sites were crossmatched with local HIV surveillance registries to identify syphilis case-persons infected with HIV before or shortly after the syphilis diagnosis. We examined HIV VL and CD4 results collected within 6 months before or after syphilis diagnosis for the coinfected cases identified...
October 1, 2015: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Daniel R Klinger, Bruno C Flores, Jeremy J Lewis, Kimmo Hatanpaa, Kevin Choe, Bruce Mickey, Samuel Barnett
INTRODUCTION: Atypical meningiomas (World Health Organization [WHO] grade II) represent a therapeutic challenge given their high recurrence rate and greater mortality compared with WHO grade I meningiomas. Traditionally, treatment has entailed attempts at gross total resection with radiation therapy reserved for residual disease or recurrences. METHODS: We retrospectively reviewed our patient database of atypical meningioma (AM) patients over the past 10 years to assess surgical and radiotherapeutic treatments administered, treatment-related complications, radiographic-clinical progression after treatment, and mortality...
September 2015: World Neurosurgery
Kumar Pichumani, Tomoyuki Mashimo, Hyeon-Man Baek, James Ratnakar, Bruce Mickey, Ralph J DeBerardinis, Elizabeth A Maher, Robert M Bachoo, Craig R Malloy, Zoltan Kovacs
(13)C NMR (nuclear magnetic resonance) spectroscopy of extracts from patient tumor samples provides rich information about metabolism. However, in isocitrate dehydrogenase (IDH)-mutant gliomas, (13)C labeling is obscured in oncometabolite 2-hydroxyglutaric acid (2 HG) by glutamate and glutamine, prompting development of a simple method to resolve the metabolites. J-coupled multiplets in 2 HG were similar to glutamate and glutamine and could be clearly resolved at pH 6. A cryogenically cooled (13)C probe, but not J-resolved heteronuclear single quantum coherence spectroscopy, significantly improved detection of 2 HG...
July 15, 2015: Analytical Biochemistry
Paul Narayan Hein, Bryan Lieber, Eliza Bruce, Blake Taylor, Geoffrey Appelboom, Mickey Abraham, E Sander Connolly
We sought to assess the impact of neoadjuvant therapy on 30 day mortality and morbidity using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Chemotherapy and radiotherapy are both often indicated for treatment of cranial or systemic malignancy but can have significant adverse effects in the postsurgical setting. Data from 2006 to 2012 were obtained from the national ACS-NSQIP database. A total of 1044 patients were identified who obtained surgery for removal of metastatic brain tumors, of whom 127 received neoadjuvant chemotherapy and 65 neoadjuvant radiotherapy...
June 2015: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Eamon B O'Reilly, Sam Barnett, Christopher Madden, Babu Welch, Bruce Mickey, Shai Rozen
PURPOSE: Traditional cranioplasty methods focus on pre-operative or intraoperative hand molding. Recently, CT-guided polyether ether ketone (PEEK) plate reconstruction enables precise, time-saving reconstruction. This case series aims to show a single institution experience with use of PEEK cranioplasty as an effective, safe, precise, reusable, and time-saving cranioplasty technique in large, complex cranial defects. METHODS: We performed a 6-year retrospective review of cranioplasty procedures performed at our affiliated hospitals using PEEK implants...
March 2015: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
Tomoyuki Mashimo, Kumar Pichumani, Vamsidhara Vemireddy, Kimmo J Hatanpaa, Dinesh Kumar Singh, Shyam Sirasanagandla, Suraj Nannepaga, Sara G Piccirillo, Zoltan Kovacs, Chan Foong, Zhiguang Huang, Samuel Barnett, Bruce E Mickey, Ralph J DeBerardinis, Benjamin P Tu, Elizabeth A Maher, Robert M Bachoo
Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using (13)C-NMR analysis of brain tumors resected from patients during infusion of (13)C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-(13)C]acetate and can do so while simultaneously oxidizing [1,6-(13)C]glucose...
December 18, 2014: Cell
Sharmistha Chakraborty, Li Li, Vineshkumar Thidil Puliyappadamba, Gao Guo, Kimmo J Hatanpaa, Bruce Mickey, Rhonda F Souza, Peggy Vo, Joachim Herz, Mei-Ru Chen, David A Boothman, Tej K Pandita, David H Wang, Ganes C Sen, Amyn A Habib
Epidermal growth factor receptor (EGFR) overexpression plays an important oncogenic role in cancer. Regular EGFR protein levels are increased in cancer cells and the receptor then becomes constitutively active. However, downstream signals generated by constitutively activated EGFR are unknown. Here we report that the overexpressed EGFR oscillates between two distinct and mutually exclusive modes of signalling. Constitutive or non-canonical EGFR signalling activates the transcription factor IRF3 leading to expression of IFI27, IFIT1 and TRAIL...
December 15, 2014: Nature Communications
Yael Velleman, Elizabeth Mason, Wendy Graham, Lenka Benova, Mickey Chopra, Oona M R Campbell, Bruce Gordon, Sanjay Wijesekera, Sennen Hounton, Joanna Esteves Mills, Val Curtis, Kaosar Afsana, Sophie Boisson, Moke Magoma, Sandy Cairncross, Oliver Cumming
Yael Velleman and colleagues argue for stronger integration between the water, sanitation, and hygiene (WASH) and maternal and newborn health sectors. Please see later in the article for the Editors' Summary.
December 2014: PLoS Medicine
Geoff Appelboom, Elvis Camacho, Mickey E Abraham, Samuel S Bruce, Emmanuel Lp Dumont, Brad E Zacharia, Randy D'Amico, Justin Slomian, Jean Yves Reginster, Olivier Bruyère, E Sander Connolly
BACKGROUND: Innovations in mobile and electronic healthcare are revolutionizing the involvement of both doctors and patients in the modern healthcare system by extending the capabilities of physiological monitoring devices. Despite significant progress within the monitoring device industry, the widespread integration of this technology into medical practice remains limited. The purpose of this review is to summarize the developments and clinical utility of smart wearable body sensors...
2014: Archives of Public Health, Archives Belges de Santé Publique
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