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Nahed, Brian

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Nahed

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Nahed, Brian
Author's Publications: search.filters.isAuthorOfPublication.17126e09-3766-4712-9ac6-756b0ec68f86

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Now showing 1 - 10 of 26
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    Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles
    (Nature Publishing Group UK, 2018) Reátegui, Eduardo; van der Vos, Kristan E.; Lai, Charles P.; Zeinali, Mahnaz; Atai, Nadia; Aldikacti, Berent; Floyd, Frederick P.; H. Khankhel, Aimal; Thapar, Vishal; Hochberg, Fred H.; Sequist, Lecia; Nahed, Brian; S. Carter, Bob; Toner, Mehmet; Balaj, Leonora; T. Ting, David; Breakefield, Xandra; Stott, Shannon
    Extracellular vesicles (EVs) carry RNA, DNA, proteins, and lipids. Specifically, tumor-derived EVs have the potential to be utilized as disease-specific biomarkers. However, a lack of methods to isolate tumor-specific EVs has limited their use in clinical settings. Here we report a sensitive analytical microfluidic platform (EVHB-Chip) that enables tumor-specific EV-RNA isolation within 3 h. Using the EVHB-Chip, we achieve 94% tumor-EV specificity, a limit of detection of 100 EVs per μL, and a 10-fold increase in tumor RNA enrichment in comparison to other methods. Our approach allows for the subsequent release of captured tumor EVs, enabling downstream characterization and functional studies. Processing serum and plasma samples from glioblastoma multiforme (GBM) patients, we can detect the mutant EGFRvIII mRNA. Moreover, using next-generation RNA sequencing, we identify genes specific to GBM as well as transcripts that are hallmarks for the four genetic subtypes of the disease.
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    Neural encoding and production of functional morphemes in the posterior temporal lobe
    (Nature Publishing Group UK, 2018) Lee, Daniel; Fedorenko, Evelina; Simon, Mirela; Curry, William; Nahed, Brian; Cahill, Dan P.; Williams, Ziv
    Morphemes are the smallest meaning-carrying units in human language, and are among the most basic building blocks through which humans express specific ideas and concepts. By using time-resolved cortical stimulations, neural recordings, and focal lesion evaluations, we show that inhibition of a small cortical area within the left dominant posterior–superior temporal lobe selectively impairs the ability to produce appropriate functional morphemes but does not distinctly affect semantic and lexical retrieval, comprehension, or articulation. Additionally, neural recordings within this area reveal the localized encoding of morphological properties and their planned production prior to speech onset. Finally, small lesions localized to the gray matter in this area result in a selective functional morpheme-production deficit. Collectively, these findings reveal a detailed division of linguistic labor within the posterior–superior temporal lobe and suggest that functional morpheme processing constitutes an operationally discrete step in the series of computations essential to language production.
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    Radiation Treatment for WHO Grade II and III Meningiomas
    (Frontiers Media S.A., 2013) Walcott, Brian; Nahed, Brian; Brastianos, Priscilla; Loeffler, Jay
    The treatment of meningiomas is tailored to their histological grade. While World Health Organization (WHO) grade I lesions can be treated with either surgery or external beam radiation, WHO Grade II and III lesions often require a combination of the two modalities. For these high-grade lesions, conventional external beam radiation is delivered to either the residual tumor or the surgical resection margin. The optimal timing of radiation, either immediately following surgical resection or at the time of recurrence, is yet to be determined. Additionally, another method of radiation delivery, brachytherapy, can be administered locally at the time of surgery for recurrent lesions. Altogether, the complex nature of WHO grade II and III meningiomas requires careful treatment planning and delivery by a multidisciplinary team.
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    Interfacility Helicopter Ambulance Transport of Neurosurgical Patients: Observations, Utilization, and Outcomes from a Quaternary Level Care Hospital
    (Public Library of Science (PLoS), 2011) Walcott, Brian; Coumans, Jean-Valery; Mian, Matthew; Nahed, Brian; Kahle, Kristopher T.
    Background: The clinical benefit of helicopter transport over ground transportation for interfacility transport is unproven. We sought to determine actual practice patterns, utilization, and outcomes of patients undergoing interfacility transport for neurosurgical conditions. Methodology/Principal Findings: We retrospectively examined all interfacility helicopter transfers to a single trauma center during 2008. We restricted our analysis to those transfers leading either to admission to the neurosurgical service or to formal consultation upon arrival. Major exclusion criteria included transport from the scene, death during transport, and transport to any area of the hospital other than the emergency department. The primary outcome was time interval to invasive intervention. Secondary outcomes were estimated ground transportation times from the referring hospital, admitting disposition, and discharge disposition. Of 526 candidate interfacility helicopter transfers to our emergency department in 2008, we identified 167 meeting study criteria. Seventy-five (45%) of these patients underwent neurosurgical intervention. The median time to neurosurgical intervention ranged from 1.0 to 117.8 hours, varying depending on the diagnosis. For 101 (60%) of the patients, estimated driving time from the referring institution was less than one hour. Four patients (2%) expired in the emergency department, and 34 patients (20%) were admitted to a non-ICU setting. Six patients were discharged home within 24 hours. For those admitted, in-hospital mortality was 28%. Conclusions/Significance: Many patients undergoing interfacility transfer for neurosurgical evaluation are inappropriately triaged to helicopter transport, as evidenced by actual times to intervention at the accepting institution and estimated ground transportation times from the referring institution. In a time when there is growing interest in health care cost containment, practitioners must exercise discretion in the selection of patients for air ambulance transport—particularly when it may not bear influence on clinical outcome. Neurosurgical evaluation via telemedicine may be one strategy for improving air transport triage.
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    Retrievable stent thrombectomy in the treatment of acute ischemic stroke: Analysis of a revolutionizing treatment technique
    (Elsevier BV, 2013) Walcott, Brian; Boehm, Kevin M.; Stapleton, Christopher; Mehta, Brijesh P.; Nahed, Brian; Ogilvy, Christopher
    Acute ischemic stroke resulting from intracranial vessel occlusion is associated with high morbidity and mortality. The mainstays of therapy are fibrinolytics and mechanical thrombectomy in properly selected patients. A new Food and Drug Administration-approved technology to perform thrombectomy, retrievable stenting, may provide superior revascularization rates and improved patient outcomes. We analyzed the cumulative human experience reported for the Trevo Pro Retrieval System (Stryker, Kalamazoo, MI, USA) and the Solitaire FR Revascularization Device (ev3, Irvine, CA, USA) as the definitive treatment for acute ischemic stroke. A literature search was undertaken to identify studies using the retrievable stents published up to September 2012. Nineteen studies identified a total of 576 patients treated with either the Trevo (n = 221) or Solitaire (n = 355) devices. Pooled data analysis identified baseline National Institutes of Health Stroke Scale scores of 18.5 ± 0.289 (standard error of the mean) and 17.9 ± 0.610, and time to recanalization of 53.9 ± 23.6 minutes and 59.0 ± 8.0 minutes for the Trevo and Solitaire groups, respectively. Recanalization was variably defined by individual studies, most commonly achieving at least a thrombolysis in cerebral infarction score of 2a–3 or a thrombolysis in myocardial infarction score of 2–3. Revascularization (83%, 82%), mortality (31%, 14%), hemorrhage (8%, 6%), device complications (5%, 6%), and good patient outcomes (51%, 47%) were found with the Trevo and Solitaire devices, respectively. Preliminary analysis reveals excellent clinical outcomes for retrievable stent technology. This may be attributable to both high rates of revascularization with a relatively short time to perfusion restoration.
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    Rapid Intraoperative Molecular Characterization of Glioma
    (American Medical Association (AMA), 2015) Shankar, Ganesh; Francis, Joshua M.; Rinne, Mikael; Ramkissoon, Shakti H.; Huang, Franklin; Venteicher, Andrew S; Akama-Garren, Elliot H.; Kang, Yun Jee; Lelic, Nina; Kim, James C.; Brown, Loreal E.; Charbonneau, Sarah K; Golby, Alexandra; Sekhar Pedamallu, Chandra; Hoang, Mai; Sullivan, Ryan; Cherniack, Andrew D.; Garraway, Levi; Stemmer-Rachamimov, Anat; Reardon, David; Wen, Patrick; Brastianos, Priscilla; Curry, William; Barker, Frederick; Hahn, William; Nahed, Brian; Ligon, Keith; Louis, David; Cahill, Daniel; Meyerson, Matthew
    IMPORTANCE: Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1). OBSERVATIONS: This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%–99%) and 100% specificity (95% CI, 95%–100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe. CONCLUSIONS AND RELEVANCE: The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations.
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    Trends in peptic ulcer disease and the identification of Helicobacter Pylori as a causative organism: Population-based estimates from the US nationwide inpatient sample
    (Medknow, 2011) Walcott, Brian; Bashinskaya, Bronislava; Nahed, Brian; Redjal, Navid; Kahle, Kristopher T.
    Background: Peptic ulcer disease can lead to serious complications including massive hemorrhage or bowel perforation. The modern treatment of peptic ulcer disease has transitioned from the control of gastric acid secretion to include antibiotic therapy in light of the identification of Helicobacter pylori as a causative infectious organism. We sought to determine trends related to this discovery by using a national database. Materials and Methods: Patient discharges with peptic ulcer disease and associated sequelae were queried from the Nationwide Inpatient Sample, 1993 to 2007, under the auspices of a data user agreement. To account for the Nationwide Inpatient Sample weighting schema, design-adjusted analyses were used. Standard error was calculated using SUDAAN software (Research Triangle International, NC, USA). Results: Decreases in the incidences of gastrointestinal perforation, gastrointestinal hemorrhage, and surgical procedures most specific to peptic ulcer disease were statistically significant over the study period [range of P value (two tailed) = 0.000 – 0.00353; significant at P < 0.001 to < 0.01]. The incidence of H. pylori rose dramatically, peaking at an estimated 97,823 cases in 1998 [SE = 3155; 95% CI = 6,184]. Since that time it has decreased and then stabilized. Conclusions:The identification of H. pylori as the causative agent in the majority of peptic ulcer disease has revolutionized the understanding and management of the disease. Medical conditions and surgical procedures associated with end-stage peptic ulcer disease have significantly decreased according to analysis of selected index categories. Resident physician education objectives may need to be modified in light of these trends. Review Criteria: We reviewed patients with peptic ulcer disease. The database used was the Nationwide Inpatient Sample, 1993 to 2007. Message for the Clinic: Medical therapy has resulted in decreased morbidity from H. pylori infection as it is the causative agent in the majority of peptic ulcer disease. Aggressive screening and treatment of this infection will lead to further reduction in morbidity.
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    Clinical features of brain metastasis from salivary gland tumors
    (Elsevier BV, 2013) Venteicher, Andrew S; Walcott, Brian; Sheth, Sameer A.; Snuderl, Matija; Patel, Anoop Premswaroop; Curry, William; Nahed, Brian
    Salivary gland tumors comprise a group of 24 tumor subtypes with a wide range of clinical behaviors and propensities for metastasis. Several prognostic factors have been identified that help predict the development of systemic metastases, most commonly to the lung, liver, or bone. Metastases to the brain are rare. To better understand the behavior of salivary gland tumors that metastasise to the brain, we performed a retrospective cohort analysis on a series of patients to highlight features of their medical and surgical management. From 2007 to 2011, a database of 4117 elective craniotomies were queried at a single institution to identify patients surgically treated for salivary gland metastases to the brain. Three patients were identified. Histologic subtypes included salivary duct carcinoma, poorly differentiated carcinoma, and papillary mucinous adenocarcinoma. They had all undergone previous treatment for their primary malignancy. The mean time to intracranial metastasis was 48 months from initial diagnosis (range, 14–91 months). Treatment for intracranial metastases included surgical resection, whole brain radiation, stereotactic radiosurgery, and chemotherapy. Intracranial metastases from salivary gland tumors are rare, present years after diagnosis of the primary tumor, and are treatable with multimodality therapy.
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    Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq
    (American Association for the Advancement of Science (AAAS), 2017) Venteicher, Andrew S; Tirosh, Itay; Hebert, Christine; Yizhak, Keren; Neftel, Cyril Ralf Alexander; Filbin, Mariella; Hovestadt, Volker; Escalante, Leah; Shaw, McKenzie; Rodman, Christopher Jiahn-Leh; Gillespie, Shawn; Dionne, Danielle; Luo, Christina; Ravichandran, Hiranmayi; Mylvaganam, Ravindra; Mount, Christopher; Onozato, Maristela Lika; Nahed, Brian; Wakimoto, Hiroaki; Curry, William; Iafrate, Anthony; Rivera, Miguel; Frosch, Matthew; Golub, Todd; Brastianos, Priscilla; Getz, Gad; Patel, Anoop Premswaroop; Monje, Michelle; Cahill, Daniel; Rozenblatt-Rosen, Orit; Louis, David; Bernstein, Bradley; Regev, Aviv; Suva, Mario
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    Reversal of warfarin associated coagulopathy with 4-factor prothrombin complex concentrate in traumatic brain injury and intracranial hemorrhage
    (Elsevier BV, 2014) Yanamadala, Vijay; Walcott, Brian; Fecci, Peter; Rozman, Peter; Kumar, Jay; Nahed, Brian; Swearingen, Brooke
    Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physicians. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p = 0.89). The time to reversal was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p < 0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p < 0.05). In this preliminary experience, PCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes.