Barton F Branstetter

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (151)410.52 Total impact

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    ABSTRACT: The goal of this study was to characterize the molecular mechanisms underlying cetuximab-mediated upregulation of HLA class I antigen processing machinery components in head and neck cancer (HNC) cells and to determine the clinical significance of these changes in cetuximab-treated HNC patients. Flow cytometry, signaling studies and chromatin immunoprecipitation (ChIP) assays were performed using HNC cells treated with cetuximab alone or with Fcγ receptor (FcγR) bearing lymphocytes to establish the mechanism of EGFR-dependent regulation of HLA APM expression. A prospective phase II clinical trial of neoadjuvant cetuximab was utilized to correlate HLA class I expression with clinical response in HNC patients. EGFR blockade triggered STAT1 activation and HLA upregulation, in a src homology-containing protein (SHP)-2 dependent fashion, more prominently in HLA-B/C than HLA-A alleles. EGFR signaling blockade also enhanced IFNγ receptor 1 (IFNAR) expression, augmenting induction of HLA class I and TAP1/2 expression by IFNγ, which was abrogated in STAT1-/- cells. Cetuximab enhanced HNC cell recognition by EGFR853-861 specific CTL, and notably enhanced surface presentation of a non-EGFR peptide (MAGE-3271-279). HLA class I upregulation was significantly associated with clinical response in cetuximab-treated HNC patients. EGFR induces HLA downregulation through SHP-2/STAT1 suppression. Reversal of HLA class I downregulation was more prominent in clinical responders to cetuximab therapy, supporting an important role for adaptive immunity in cetuximab antitumor activity. Abrogating EGFR-induced immune escape mechanisms and restoring STAT1 signaling to reverse HLA downregulation using cetuximab should be combined with strategies to enhance adaptive cellular immunity. Copyright © 2015, American Association for Cancer Research.
    05/2015; 3(8). DOI:10.1158/2326-6066.CIR-15-0053
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    ABSTRACT: To determine the accuracy of pretreatment, contrast-enhanced computed tomography (CT) in the diagnosis of extracapsular spread (ECS) in cervical lymph node metastases from p16-positive head-and-neck squamous cell carcinoma (HNSCC). Retrospective observational study. Sixty-five (n = 65) patients diagnosed between 2004 and 2013 with p16-positive HNSCC and with cervical lymph node metastases measuring at least 1 centimeter in diameter on pathological assessment were included. All patients underwent primary surgical treatment. Subjects' preoperative contrast-enhanced neck CT scans were independently assigned a score for the likelihood of ECS (5-point scale) by two board-certified neuroradiologists. Receiver-operating characteristic curves were generated, and optimal sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for each radiologist. On histological analysis, the majority of patients (58%; 38/65) were found to have ECS, and 29% (19/65) of patients had ≥ three metastatic lymph nodes. For radiologist 1, PPV and NPV for ECS detection were 72% (95% confidence interval (CI), 53%-87%) and 53% (95% CI, 36%-70%), respectively. For radiologist 2, PPV and NPV for ECS detection were 82% (95% CI, 60 %-95%) and 53% (95% CI, 38%-69%), respectively. CT is not a reliable method for determining the presence of ECS in p16-positive HNSCC patients. 4. Laryngoscope, 2015. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.
    The Laryngoscope 05/2015; 125(7). DOI:10.1002/lary.25140 · 2.14 Impact Factor
  • R.M. Srivastava · S. Trivedi · L. Wang · R.R. Sheethala · S. Ferrone · B.F. Branstetter · R.L. Ferris ·

    Oral Oncology 05/2015; 51(5):e37. DOI:10.1016/j.oraloncology.2015.02.033 · 3.61 Impact Factor
  • Alan S. Leung · Tanya J. Rath · Marion A. Hughes · Seungwon Kim · Barton F. Branstetter ·
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    ABSTRACT: The optimal timing for initial post-treatment FDG-PET/CT scan after definitive treatment of head and neck squamous cell carcinoma is unclear. Retrospective review of 247 patients with definitively treated non-metastatic head and neck squamous cell carcinoma. First post-treatment PET/CT scans were grouped into: <7 weeks, 7 to 10 weeks, 11 to 14 weeks, and ≥15 weeks. Scans were categorized as positive or negative and accuracy of scans was calculated for each group using biopsy, subsequent imaging, or clinical follow-up for one year after treatment as a reference standard. 67 of the 247 patients (27.1%) had treatment failure. Scans performed at <7 weeks were less accurate than all other time intervals (p<0.05). Scans performed at all other intervals were similar in accuracy. First post-treatment PET/CT can be obtained as early as 2 months after therapy. Scans performed earlier than 2 months have lower accuracy. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Head & Neck 04/2015; DOI:10.1002/hed.24112 · 2.64 Impact Factor
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    ABSTRACT: Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m(2) on day -7 and then 250 mg/m(2) on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 03/2015; 91(3):480-8. DOI:10.1016/j.ijrobp.2014.11.023 · 4.26 Impact Factor
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    ABSTRACT: Given the problems of overuse of medical technology and the current burden of health care cost in the United States, it is important to establish clear imaging guidelines to diagnose conditions such as juvenile ossifying fibroma (JOF). This study compared the efficacy of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of JOF and thus could aid establishing such guidelines. Radiologic criteria were established by 2 radiologists to compare the efficacy of CT and MRI in the evaluation of JOF. The following parameters were compared: presence of a well-defined corticated border, presence of a well-delineated internal calcified component, fluid-to-fluid levels, and anatomic extent of the lesion. Six patients diagnosed with JOF of the craniofacial bones from 2002 to 2013 had preoperative CT and MRI studies available for review. After review of CT and MRI images, fluid-to-fluid levels and anatomic extent of the lesions were comparable on CT and MRI. However, the corticated borders and the internal calcified component were better defined on CT images, which also enabled for distinction between the 2 subtypes of JOF. No MRI characteristics were identified that allowed for this distinction. Based on these findings, CT is an adequate and preferable imaging modality in the evaluation of JOF. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
    Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 01/2015; 73(7). DOI:10.1016/j.joms.2015.01.013 · 1.43 Impact Factor
  • M.A. Hughes · B.F. Branstetter · A.M. Frederickson · J.E. Oskin · U. Yankevich · R.F. Sekula ·
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    ABSTRACT: Hemifacial spasm, a syndrome of unilateral facial nerve hyperactive dysfunction, is a severe and disabling condition that negatively impacts the quality of life of patients. Vascular compression of the facial nerve is the most common etiology of hemifacial spasm, but not all segments of the nerve are vulnerable to compression. The vulnerable segment begins at the pontomedullary sulcus medially and extends laterally until approximately 4 mm lateral to the facial nerve's detachment point from the brain stem. Importantly, and unknown to many neuroradiologists, the facial nerve is attached to the pons for approximately 1 cm along the undersurface of the pons, and most cases of vascular compression causing hemifacial spasm occur along this “attached” segment. Knowledge of the anatomy and vulnerable portions of the facial nerve is critical to correctly identify patients who are candidates for microvascular decompression, to locate the culprit arterial vessel, and to guide operative management.Learning Objective: Recognize the imaging appearance of vascular compression of the susceptible portion of the facial nerve in patients presenting with hemifacial spasm.
    01/2015; 5(1). DOI:10.3174/ng.1150097
  • David L Weiss · Woojin Kim · Barton F Branstetter · Luciano M Prevedello ·
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    ABSTRACT: With the increasing prevalence of PACS over the past decade, face-to-face image review among health care providers has become a rarity. This change has resulted in increasing dependence on fast and accurate communication in radiology. Turnaround time expectations are now conveyed in minutes rather than hours or even days. Ideal modern radiology communication is a closed-loop cycle with multiple interoperable applications contributing to the final product. The cycle starts with physician order entry, now often performed through the electronic medical record, with clinical decision support to ensure that the most effective imaging study is ordered. Radiology reports are now almost all in electronic format. The majority are produced using speech recognition systems. Optimization of this software use can alleviate some, if not all, of the inherent user inefficiencies in this type of reporting. Integrated third-party software applications that provide data mining capability are extremely helpful in both academic and clinical settings. The closed-loop ends with automated communication of imaging results. Software products for this purpose should facilitate use of levels of alert, automated escalation to providers, and recording of audit trails of reports received. The multiple components of reporting should be completely interoperable with each other, as well as with the PACS, the RIS, and the electronic medical record. This integration will maximize radiologist efficiency and minimize the possibility of communication error. Copyright © 2014. Published by Elsevier Inc.
    Journal of the American College of Radiology: JACR 12/2014; 11(12 Pt B):1226-37. DOI:10.1016/j.jacr.2014.09.009 · 2.84 Impact Factor
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    ABSTRACT: A minority of patients who undergo microvascular decompression for hemifacial spasm do not improve after the first operation. We sought to determine the most common locations of unaddressed neurovascular contact in patients with persistent or recurrent hemifacial spasm despite prior microvascular decompression. Eighteen patients with a history of a microvascular decompression presented with persistent hemifacial spasm. All patients underwent thin-section steady-state free precession MR imaging. Fourteen patients underwent repeat microvascular decompression at our institution. Images were evaluated for the following: the presence of persistent vascular compression of the facial nerve, type of culprit vessel (artery or vein), name of the culprit artery, segment of the nerve in contact with the vessel, and location of the point of contact relative to the existing surgical pledget. The imaging findings were compared with the operative findings. In 12 of the 18 patients (67%), persistent vascular compression was identified by imaging. In 11 of these 12 patients, the culprit vessel was an artery. Compression of the attached segment (along the ventral surface of the pons) was identified in most patients (58%, 7/12). The point of contact was proximal to the surgical pledget in most patients (83%, 10/12). The imaging interpretation was concordant with the surgical results regarding artery versus vein in 86% of cases and regarding the segment of the nerve contacted in 92%. In patients with persistent hemifacial spasm despite microvascular decompression, the unaddressed vascular compression is typically proximal to the previously placed pledget, usually along the attached segment of the nerve. Re-imaging with high-resolution T2-weighted MR imaging will usually identify the culprit vessel. © 2015 American Society of Neuroradiology.
    American Journal of Neuroradiology 11/2014; 36(4). DOI:10.3174/ajnr.A4174 · 3.59 Impact Factor
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    Galal Omami · Dania Tamimi · Barton F. Branstetter ·
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    ABSTRACT: A combination of positron emission tomography (PET) with 18F-labeled fluoro-2-deoxyglucose (18F-FDG) and computed tomography (18F-FDG-PET/CT) has increasingly become a widely used imaging modality for the diagnosis and management of head and neck cancer. On the basis of both recent literature and our professional experience, we present a set of principles with pictorial illustrations and clinical applications of FDG-PET/CT in the evaluation and management planning of squamous cell carcinoma of the oral cavity and oropharynx. We feel that this paper will be of interest and will aid the learning of oral and maxillofacial radiology trainees and practitioners.
    Imaging Science Journal The 11/2014; 44(4):325-332. DOI:10.5624/isd.2014.44.4.325 · 0.30 Impact Factor
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    ABSTRACT: Objectives/HypothesisThe goal of this study was to present a classification based on the degree of pneumatization of the sphenoid sinus in the coronal plane that can be used to instruct preoperative planning for endoscopic endonasal surgery (EES).Study DesignObservational anatomical study.Methods The geometry of sphenoid sinus pneumatization was characterized (n = 204 hemisinus) on high-resolution computed tomography scans, and its associations with the location of the foramen rotundum (FR) and the vidian canal (VC) were measured. Based on these findings, we propose a simple classification of pneumatization of the sphenoid sinus relevant for EES.ResultsThe lateral recess of the sphenoid sinus was pneumatized lateral to the FR in the coronal plane in 54% of patients. The distance separating the FR and the VC correlated strongly with the depth of the lateral recess. Based on these findings, we propose three types of pneumatization: type I, where the pneumatization extends from the midline to the medial edge of the VC (25%); type II, where the pneumatization reaches the medial edge of the FR (39%); and type III, where the pneumatization extends beyond the medial border of the FR (37%).Conclusions The proposed sphenoid sinus pneumatization classification in the coronal plane is simple and reproducible. It predicts the distance between vidian and maxillary nerve, determines the size of the surgical window to access the middle cranial fossa transnasally, and instructs on the potential risk to neurovascular structures during surgery.Level of Evidence4 Laryngoscope, 2014
    The Laryngoscope 11/2014; 125(3). DOI:10.1002/lary.24989 · 2.14 Impact Factor
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    ABSTRACT: We present the first report of a case of hemifacial spasm caused by an anomalous, enlarged branch of the ascending pharyngeal artery and treated with microvascular decompression. Clinicians must appreciate unusual causes of hemifacial spasm so that patients are not denied a curative operation due to atypical radiographic findings.
    British Journal of Neurosurgery 09/2014; DOI:10.3109/02688697.2014.957158 · 0.96 Impact Factor
  • J. Vargo · R.L. Ferris · J. Ohr · D.A. Clump · K. Davis · J. Johnson · M. Gibson · B.F. Branstetter · D.E. Heron ·

    International journal of radiation oncology, biology, physics 09/2014; 90(1):S122. DOI:10.1016/j.ijrobp.2014.05.558 · 4.26 Impact Factor
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    ABSTRACT: Hemifacial spasm (HFS) is a condition that may severely reduce patients' quality of life. We sought to determine the sensitivity and specificity of thin-slice T2 magnetic resonance imaging (MRI) for detecting vascular compression in HFS patients. Prospective information was collected on 28 patients with HFS who presented to our center between March 2011 and March 2012 with thin-slice T2 MR imaging. The sensitivity and specificity for differentiating patients from controls were calculated. Sensitivities were 78.6% and 92.9% for the blinded radiologists and 75% for the partially blinded neurosurgeon. Specificities were 42.9% and 28.6% for the blinded radiologists and 75% for the partially blinded neurosurgeon. Magnetic resonance imaging of the facial nerve can guide clinicians in selecting patients who are good surgical candidates. Thin-slice T2 MRI should be viewed as supportive rather than diagnostic. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 09/2014; 29(10). DOI:10.1002/mds.25947 · 5.68 Impact Factor
  • Jonas T Johnson · Barton F Branstetter ·
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    ABSTRACT: Combined positron emission tomography with simultaneous computed tomography (PET/CT performed using 18F-fluorodeoxyglucose [FDG] as a radiopharmaceutical) results in improvement in anatomic localization of tumor. This review explores the contemporary application of PET/CT to pretreatment assessment, posttreatment monitoring, and subsequent treatment planning for patients with squamous carcinoma of the head and neck. Contemporary publications on the use of PET/CT in head and neck oncology are reviewed and synthesized. This review presents selected literature interpreted by expert opinion. PET/CT is highly sensitive in staging of patients with squamous cancer of the head and neck. The sensitivity is limited by tumor size, and PET/CT cannot currently replace the information obtained from elective neck dissection in the assessment of cervical metastases. In the setting of posttreatment monitoring, PET/CT allows for identification of persistent carcinoma prior to clinical observation in approximately two-thirds of cases. However, contemporary reports do not allow assessment of cost effectiveness, and they do not allow determination if the application of PET/CT in this setting results in improved treatment outcomes. PET/CT is insensitive to evaluation of patients with glandular tumors, and those with low volume tumors and cystic metastases. PET/CT requires further evaluation before recommendations can be made regarding comparative effectiveness when compared to CT or MRI for posttreatment monitoring. The improved sensitivity and specificity of PET/CT during treatment planning justifies its use in this setting for patients with advanced stage squamous cancer of the head and neck. Laryngoscope, 2014.
    The Laryngoscope 04/2014; 124(4). DOI:10.1002/lary.23942 · 2.14 Impact Factor
  • Jason L Yu · Barton F Branstetter · Carl H Snyderman ·
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    ABSTRACT: The function of the paranasal sinuses is a topic of debate. One hypothesis suggested has been that sinuses act as a "crumple zone," serving to protect the contents of the head from impact. In this study, we examine the interactions of the frontal sinus and the brain in the setting of head trauma. Our formal hypothesis is that frontal sinus volume is less in head trauma patients with contusion than in head trauma patients without contusion. Computed tomographic (CT) scans of patients who sustained blunt head trauma performed at the University of Pittsburgh Medical Center from 2007 to 2012 were reviewed retrospectively. Inclusion criteria were presence of blunt trauma and complete brain and maxillofacial CT scan. Exclusion criteria included patients with incomplete imaging, imaging unrelated to trauma, previous cranial injury, and penetrating trauma.With the use of maxillofacial CT scans, height, depth, and width were measured, and a cubical approximation of volume was determined for each frontal sinus. Presence of frontal sinus fracture was considered an indicator of high-impact trauma. Grading of brain contusion severity was performed using head CT scans. A scale of 0 to 5 was used based on the Marshall Criteria.Categorical data were analyzed using the χ or Fisher's exact test. Continuous data were analyzed using Student's t test or analysis of variance. p < 0.05 was considered statistically significant. Among patients with frontal sinus fracture, the average sinus volume of those without contusion was 32.72 mL, while the average sinus volume of those with brain contusion was 21.85 mL (p = 0.023). Thus, the volume of the frontal sinuses was 33% less in patients with contusion than in patients without contusion. Our study supports the theory that the frontal sinuses impart a protective advantage against frontal brain contusion. The dynamics of head injury and force distribution during trauma may be the basis for more advanced protective devices. Prognostic study, level III.
    02/2014; 76(2):488-92. DOI:10.1097/TA.0b013e3182aaa4bd
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    ABSTRACT: IMPORTANCE At many institutions, computed tomography with iodinated intravenous contrast medium is the preferred imaging modality for staging of the neck in squamous cell carcinoma of the head and neck. However, few studies have specifically assessed the diagnostic accuracy of computed tomography for determining the presence or absence of extracapsular spread (ECS). OBJECTIVE To determine the accuracy of modern, contrast-enhanced, multidetector computed tomography in the diagnosis of ECS of cervical lymph node metastases from squamous cell carcinoma of the head and neck. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study at an academic tertiary referral center among 100 consecutive patients between May 1, 2007, and February 1, 2012, who underwent a lateral cervical neck dissection for squamous cell carcinoma of the head and neck with neck metastases of at least 1 cm in diameter on pathologic assessment. Exclusion criteria included malignant neoplasms other than squamous cell carcinoma, a delay in surgery longer than 6 weeks from the time of staging computed tomography, and prior treatment of the neck or recurrent disease or a second primary. MAIN OUTCOMES AND MEASURES Each patient was independently assigned a subjective score for the presence of ECS by 2 Certificate of Added Qualification-certified neuroradiologists according to a 5-point scale. Receiver operating characteristic curves were generated, and sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for each observer. RESULTS The areas under the receiver operating characteristic curve for observers 1 and 2 are 0.678 (95% CI, 0.578-0.768) and 0.621 (95% CI, 0.518-0.716), respectively. For observer 1, the positive and negative predictive values for the detection of ECS were 84% (95% CI, 68%-93%) and 49% (95% CI, 36%-62%), respectively. For observer 2, the positive and negative predictive values for the detection of ECS were 71% (95% CI, 57%-82%) and 48% (95% CI, 32%-64%), respectively. CONCLUSIONS AND RELEVANCE Computed tomography cannot be used to reliably determine the presence of pathologic ECS. Radiologic findings suggestive of ECS should not be relied on for treatment planning in squamous cell carcinoma of the head and neck.
    JAMA Otolaryngology - Head and Neck Surgery 09/2013; 139(11). DOI:10.1001/jamaoto.2013.4491 · 1.79 Impact Factor
  • L Alhilali · S-H Seo · B F Branstetter · S Fakhran ·
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    ABSTRACT: Background and purpose: Globus sensation is common and difficult to treat. The purpose of our study was to compare the diagnostic and therapeutic efficacy of barium esophagram and neck CT in patients with isolated globus sensation, to determine which of these modalities should be preferred in the evaluation of this condition. Materials and methods: We retrospectively identified patients presenting with isolated globus sensation from January 1, 2005, to December 31, 2012, who underwent neck CT or barium esophagram. We calculated the proportion of patients with abnormal findings, tabulated the nature of the abnormality, and reviewed the medical records to determine whether imaging changed management. Results: One hundred forty-eight neck CTs and 104 barium esophagrams were included. Five (3.4%) patients with neck CTs and 4 (3.9%) with barium esophagrams demonstrated significant findings related to the history of globus sensation. Of these, 1 (0.7%) neck CT and 1 (1.0%) barium esophagram resulted in a change in clinical management. Conclusions: Imaging evaluation of the patient with uncomplicated globus sensation is unlikely to identify clinically significant imaging findings and is very unlikely to result in a change in clinical management, with a combined therapeutic efficacy of 0.8%. Thus, the routine use of imaging in the evaluation of patients with globus sensation cannot be recommended.
    American Journal of Neuroradiology 08/2013; 35(2). DOI:10.3174/ajnr.A3683 · 3.59 Impact Factor
  • Jacob G Robison · Todd D Otteson · Barton F Branstetter · Jason C Fowler · David H Chi ·

    JAMA Otolaryngology - Head and Neck Surgery 07/2013; 139(7):747-8. DOI:10.1001/jamaoto.2013.3450 · 1.79 Impact Factor
  • Article: Reply.
    Barton F Branstetter · Ming-Eng Liu · Edward J Escott ·

    American Journal of Roentgenology 06/2013; 200(6):W695. DOI:10.2214/AJR.12.10409 · 2.73 Impact Factor