Publications by authors named "Ashley Kita"

15 Publications

  • Page 1 of 1

In Response to Letter to the Editor Regarding: Prognostic Value of Tumor Staging: Predicting Nodal Metastases in Cutaneous Squamous Cell Carcinoma.

Laryngoscope 2021 02 8;131(2):E444. Epub 2020 Aug 8.

David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, California, U.S.A.

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http://dx.doi.org/10.1002/lary.28982DOI Listing
February 2021

Implantable Drug Reservoir Devices for Inner Ear Delivery of Pharmacotherapeutics.

Otolaryngol Head Neck Surg 2020 10 2;163(4):791-798. Epub 2020 Jun 2.

Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Objective: Cisplatin is a platinum-based chemotherapeutic drug that secondarily induces toxicity in inner ear sensory epithelia, contributing to auditory and vestibular dysfunction. We describe the creation of a drug reservoir device (DRD) to combat this ototoxicity for the duration of chemotherapy. As ototoxic side effects of chemotherapy may limit an oncologist's ability to prescribe first-line agents such as cisplatin, mitigating such devastating effects through prolonged topical therapy would be tremendously valuable.

Study Design: We investigated (1) the ability of an electrospun polylactic acid DRD to provide prolonged delivery of the posited otoprotectant metformin and (2) the development of an in vitro model utilizing Sh-Sy5y human neuroblastoma cells to assess the efficacy of metformin in reducing cisplatin-induced toxicity.

Setting: Neurophysiology laboratory.

Methods: Basic science experiments were performed to assess DRD properties and metformin's effects on cisplatin toxicity in culture.

Results: We found that DRDs with increasing polylactic acid concentrations exhibited metformin release for up to 8 weeks. In modeling elution across the round window in vitro, continued elution of metformin was observed for at least 6 weeks, as quantified by spectrophotometry. Unfortunately, metformin did not exhibit protective efficacy in this model using Sh-Sy5y cells.

Conclusion: While metformin was not found to be protective in Sh-Sy5y cells, these results suggest that an electrospun DRD can provide a tailorable drug delivery system providing medication for the duration of chemotherapy treatment. This represents a novel drug delivery system and efficacy screening assay with broad clinical applications in personalized delivery of inner ear therapies.
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http://dx.doi.org/10.1177/0194599820930229DOI Listing
October 2020

Prognostic Value of Tumor Staging: Predicting Nodal Metastases in Cutaneous Squamous Cell Carcinoma.

Laryngoscope 2021 01 25;131(1):E170-E175. Epub 2020 Mar 25.

David Geffen School of Medicine, University of California, Los Angeles, California, U.S.A.

Objectives: Determine the ability of three staging systems to stratify the risk of nodal metastases in cases of cutaneous squamous cell carcinoma (cSCC). Examine differential staging of tumors across the three systems and the resulting implications for clinical decision making.

Study Design: Retrospective chart review.

Methods: This study included 118 patients who underwent excision of primary cSCC of the head and neck as well as elective neck dissection for the same tumor between 2006 and 2017. Tumors were staged using the 2010 7th edition American Joint Committee on Cancer (AJCC 7) staging system, the 2016 8th edition AJCC staging system (AJCC 8), and the Brigham and Women's Hospital (BWH) alternative tumor staging system published in 2013.

Results: There were 28 patients (23.7%) with positive nodal metastases at the time of tumor excision. Almost all tumors staged as tumor (T)2 using AJCC 7 were upstaged to T3 or T4 using the new AJCC 8, and these two groups accounted for the majority of the nodal metastases. Similarly, the BWH-staged T3 group contained the highest number of tumors with nodal metastases. None of the three staging systems significantly stratified tumors in a manner that predicted the presence of nodal metastases.

Conclusion: Individuals with cSCC tumors staged T3 or higher in the AJCC 8 and BWH staging systems should undergo neck dissection, whereas those with lower staging should be discussed with the patient on a case-by-case basis.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lary.28633DOI Listing
January 2021

Rapid Diagnostic Test Kit for Point-of-Care Cerebrospinal Fluid Leak Detection.

SLAS Technol 2020 02 22;25(1):67-74. Epub 2019 Sep 22.

Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California Los Angeles, Los Angeles, CA, USA.

Cerebrospinal fluid (CSF) leaks can occur when there is communication between the intracranial cavities and the external environment. They are a common and serious complication of numerous procedures in otolaryngology, and if not treated, persistent leaks can increase a patient's risk of developing life-threatening complications such as meningitis. As it is not uncommon for patients to exhibit increased secretions postoperatively, distinguishing normal secretions from those containing CSF can be difficult. Currently, there are no proven, available tests that allow a medical provider concerned about a CSF leak to inexpensively, rapidly, and noninvasively rule out the presence of a leak. The gold standard laboratory-based test requires that a sample be sent to a tertiary site for analysis, where days to weeks may pass before results return. To address this, our group recently developed a semiquantitative, barcode-style lateral-flow immunoassay (LFA) for the quantification of the beta-trace protein, which has been reported to be an indicator of the presence of CSF leaks. In the work presented here, we created a rapid diagnostic test kit composed of our LFA, a collection swab, dilution buffers, disposable pipettes, and instructions. Validation studies demonstrated excellent predictive capabilities of this kit in distinguishing between clinical specimens containing CSF and those that did not. Our diagnostic kit for CSF leak detection can be operated by an untrained user, does not require any external equipment, and can be performed in approximately 20 min, making it well suited for use at the point of care. This kit has the potential to transform patient outcomes.
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http://dx.doi.org/10.1177/2472630319877377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980299PMC
February 2020

Perilymphatic Fistula After Penetrating Ear Trauma.

Clin Pract Cases Emerg Med 2019 May 4;3(2):115-118. Epub 2019 Mar 4.

David Geffen School of Medicine at the University of California Los Angeles, Department of Head and Neck Surgery, Los Angeles, California.

Pneumolabyrinth, defined as air within the labyrinth on high-resolution computed tomography, suggests that a perilymphatic fistula (PLF) is present. PLF describes an abnormal communication between the middle and inner ear, and can result in deafness, vertigo, and imbalance. In the setting of a penetrating injury to the temporal bone or inner ear, pneumolabyrinth should trigger prompt otolaryngology consultation and urgent surgical exploration. We describe a case in which a 49-year-old male presented with a traumatic PLF secondary to penetrating ear injury. Imaging demonstrated extensive pneumolabyrinth. Despite delay in diagnosis, expeditious surgical intervention resulted in successful preservation of inner ear function.
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http://dx.doi.org/10.5811/cpcem.2019.1.37404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497203PMC
May 2019

Point-of-Care Cerebrospinal Fluid Detection.

Otolaryngol Head Neck Surg 2018 11 24;159(5):824-829. Epub 2018 Jul 24.

1 Department of Head and Neck Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

Objective: A cerebrospinal fluid leak is one of the most serious complications in otolaryngology. It may occur as a result of injury to the skull base, typically traumatic or iatrogenic. While the presence of a leak is often discerned in the emergent setting, distinguishing normal secretions from those containing cerebrospinal fluid can be difficult during postoperative visits in the clinic. As most current laboratory-based assays are labor intensive and require several days to result, we aim to develop a more user-friendly and rapid point-of-care cerebrospinal fluid detection device.

Study Design: Our laboratory developed a barcode-style lateral-flow immunoassay utilizing antibodies for beta-trace protein, a protein abundant in and specific for cerebrospinal fluid, with a concentration of 1.3 mg/L delineating a positive result.

Setting: Tertiary medical center.

Subjects And Methods: Tests with known concentrations of resuspended beta-trace protein and the contents of discarded lumbar drains (presumed to contain cerebrospinal fluid) were performed to validate our novel device.

Results: Our results demonstrate the ability of our device to semiquantitatively identify concentrations of beta-trace protein from 0.3-90 mg/L, which is within the required range to diagnose a leak, thus making beta-trace protein an excellent target for rapid clinical detection.

Conclusion: Herein we detail the creation and initial validation of the first point-of-care cerebrospinal fluid detection device. This device is a feasible method to more efficiently and cost-effectively identify cerebrospinal fluid leaks, minimize costs, and improve patient outcomes.
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http://dx.doi.org/10.1177/0194599818789075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980298PMC
November 2018

Intraosseous mucoepidermoid carcinoma: Outcome review.

Laryngoscope 2018 05 22;128(5):1083-1092. Epub 2017 Aug 22.

Department of Head and Neck Surgery, University of California Irvine, Irvine.

Objective: Identify the effect of patient characteristics, disease traits, and treatment modality on patient outcomes in the rare disease process of intraosseous mucoepidermoid carcinoma.

Study Design: Retrospective review of institutional case records and literature.

Methods: This study includes one case report, a literature review of the MEDLINE database from 1950 through June 2017 using keywords "intraosseous" and "mucoepidermoid," and a query of the University of California, Los Angeles, Department of Pathology database for all documented cases of intraosseous mucoepidermoid carcinoma of the head and neck.

Results: Indicators of poorer prognosis were male gender (P = 0.0071) and higher histological grade (P = 0.0095). Lesion site, size, association with odontogenic cyst, and treatment type did not have a statistically significant correlation with patient outcomes. There also was no statistically significant correlation observed between treatment modality and recurrent or progressive disease when stratified by histological grade of the cancer.

Conclusion: This study identified male gender and high histological tumor grade as poor prognostic indicators; however, it did not reveal a statistically significant relationship between treatment modality and patient outcomes. Data regarding patient outcomes following treatment was limited due to loss to follow-up, suggesting that further investigation is required. Based on this review, decisions regarding treatment should be clinically guided and individually tailored to the patient's baseline health, disease severity, and the patient's treatment goals. A multi-disciplinary conference, as was utilized in the presented case report, may be the best approach to treatment planning for these patients at this time.

Level Of Evidence: 4. Laryngoscope, 128:1083-1092, 2018.
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http://dx.doi.org/10.1002/lary.26832DOI Listing
May 2018

Hemangioma.

Ear Nose Throat J 2016 Jan;95(1):19-20

Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

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http://dx.doi.org/10.1177/014556131609500101DOI Listing
January 2016

Acromegaly: otolaryngic manifestations following pituitary surgery.

Am J Otolaryngol 2015 Jul-Aug;36(4):521-5. Epub 2015 Mar 7.

Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles (UCLA) Medical Center, Los Angeles, CA. Electronic address:

Objectives: Acromegalics present with a wide range of otolaryngic symptoms, including rhinosinusitis, changes in facial appearance, obstructive sleep apnea (OSA), and voice disturbances. Treatment typically involves transnasal-transsphenoidal (TNTS) resection of the offending pituitary adenoma. In this study, we identify the prevalence of otolaryngic symptoms of acromegalic patients, and evaluate Sinonasal Outcome Test (SNOT-22) scores preceding and following pituitary resection.

Design: Retrospective chart review.

Setting: Tertiary academic medical center.

Participants: Patients diagnosed with acromegaly who underwent surgical resection of a growth-hormone secreting pituitary adenoma between August 2010 and September 2013.

Main Outcome Measures: Subjects were asked to complete questionnaires detailing otolaryngic symptoms as well as SNOT-22 surveys before and after TNTS surgery. A Student's t-test was used to compare preoperative and postoperative SNOT-22 scores.

Results: Twenty-five patients underwent pituitary surgery for acromegaly. Acromegalic patients were found to have macroglossia (60%), OSA or sleep-disordered breathing (52%), thyroid neoplasia (20%), hearing loss/tinnitus (20%), sinonasal symptoms (16%), and parathyroid pathology (8%). Differences in preoperative and postoperative SNOT-22 scores were not statistically significant.

Conclusion: Acromegalics present with assorted otolaryngic complaints. Routine screening of all acromegalics with sleep evaluations (for both surgical and perioperative planning), thyroid ultrasound, and audiologic testing should be strongly considered.
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http://dx.doi.org/10.1016/j.amjoto.2015.03.001DOI Listing
March 2016

Worsening headache and nasal congestion. Lobular capillary hemangioma.

JAMA Otolaryngol Head Neck Surg 2015 Apr;141(4):387-8

Department of Head and Neck Surgery, University of California, Los Angeles, Los Angeles.

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http://dx.doi.org/10.1001/jamaoto.2014.3539DOI Listing
April 2015

Sinonasal lymphoma: case series and review of the literature.

Int Forum Allergy Rhinol 2014 Aug 23;4(8):670-4. Epub 2014 Apr 23.

Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA.

Background: Sinonasal lymphoma is a rare rhinologic entity. We present a case series and review the literature surrounding the diagnosis and management of this disease.

Methods: A pathology database spanning 22 years at a tertiary care center was searched for a diagnosis of lymphoma in the paranasal sinuses or the nasal cavity. Seventeen cases were identified, and retrospective chart review was performed.

Results: Maxillary and ethmoid sinuses were affected more frequently (n = 8 patients each) than sphenoid and frontal sinuses (n = 5 patients each). Histologically, the most common type was diffuse large B-cell lymphoma (53%, 9 patients), followed by extranodal natural killer/T-cell lymphoma (ENKL, 21%, 3 patients). Presenting symptoms included nasal obstruction and rhinorrhea (53%, 9 patients) and diplopia (18%, 3 patients); and radiographic imaging demonstrated a discrete mass (59%, 10 patients), sinus opacification (53%, 9 patients), and/or bony erosion (35%, 6 patients). Treatment included chemotherapy alone (71%, 12 patients), chemotherapy and radiation (6%, 1 patient), and radiation alone (6%, 1 patient). The 2-year and 5-year overall survival rates were 75% and 53%, respectively, whereas disease-free 2-year and 5-year survival rates were 70% and 49%, respectively.

Conclusion: Lymphoma of the nasal cavity and paranasal sinuses is extremely rare, may mimic benign processes, and may manifest either in an isolated fashion or in conjunction with systemic disease. B-cell lymphomas, a more favorable diagnosis, account for a majority of cases, whereas ENKL is associated with rapid disease progression and death. Chemotherapy and radiation are the main therapies. Histologic diagnosis is of paramount importance, and clinicians must remain cognizant of this entity to differentiate it from other sinonasal malignancies.
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http://dx.doi.org/10.1002/alr.21337DOI Listing
August 2014

Endothelialized microfluidics for studying microvascular interactions in hematologic diseases.

J Vis Exp 2012 Jun 22(64). Epub 2012 Jun 22.

Department of Pediatrics, Emory University School of Medicine, Georgia, USA. .

Advances in microfabrication techniques have enabled the production of inexpensive and reproducible microfluidic systems for conducting biological and biochemical experiments at the micro- and nanoscales (1,2). In addition, microfluidics have also been specifically used to quantitatively analyze hematologic and microvascular processes, because of their ability to easily control the dynamic fluidic environment and biological conditions(3-6). As such, researchers have more recently used microfluidic systems to study blood cell deformability, blood cell aggregation, microvascular blood flow, and blood cell-endothelial cell interactions(6-13).However, these microfluidic systems either did not include cultured endothelial cells or were larger than the sizescale relevant to microvascular pathologic processes. A microfluidic platform with cultured endothelial cells that accurately recapitulates the cellular, physical, and hemodynamic environment of the microcirculation is needed to further our understanding of the underlying biophysical pathophysiology of hematologic diseases that involve the microvasculature. Here, we report a method to create an "endothelialized" in vitro model of the microvasculature, using a simple, single mask microfabrication process in conjunction with standard endothelial cell culture techniques, to study pathologic biophysical microvascular interactions that occur in hematologic disease. This "microvasculature-on-a-chip" provides the researcher with a robust assay that tightly controls biological as well as biophysical conditions and is operated using a standard syringe pump and brightfield/fluorescence microscopy. Parameters such as microcirculatory hemodynamic conditions, endothelial cell type, blood cell type(s) and concentration(s), drug/inhibitory concentration etc., can all be easily controlled. As such, our microsystem provides a method to quantitatively investigate disease processes in which microvascular flow is impaired due to alterations in cell adhesion, aggregation, and deformability, a capability unavailable with existing assays.
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http://dx.doi.org/10.3791/3958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471282PMC
June 2012

In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology.

J Clin Invest 2012 Jan 12;122(1):408-18. Epub 2011 Dec 12.

Department of Bioengineering, University of California, Berkeley, California, USA.

In hematologic diseases, such as sickle cell disease (SCD) and hemolytic uremic syndrome (HUS), pathological biophysical interactions among blood cells, endothelial cells, and soluble factors lead to microvascular occlusion and thrombosis. Here, we report an in vitro "endothelialized" microfluidic microvasculature model that recapitulates and integrates this ensemble of pathophysiological processes. Under controlled flow conditions, the model enabled quantitative investigation of how biophysical alterations in hematologic disease collectively lead to microvascular occlusion and thrombosis. Using blood samples from patients with SCD, we investigated how the drug hydroxyurea quantitatively affects microvascular obstruction in SCD, an unresolved issue pivotal to understanding its clinical efficacy in such patients. In addition, we demonstrated that our microsystem can function as an in vitro model of HUS and showed that shear stress influences microvascular thrombosis/obstruction and the efficacy of the drug eptifibatide, which decreases platelet aggregation, in the context of HUS. These experiments establish the versatility and clinical relevance of our microvasculature-on-a-chip model as a biophysical assay of hematologic pathophysiology as well as a drug discovery platform.
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http://dx.doi.org/10.1172/JCI58753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248292PMC
January 2012

Microenvironmental geometry guides platelet adhesion and spreading: a quantitative analysis at the single cell level.

PLoS One 2011 20;6(10):e26437. Epub 2011 Oct 20.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.

To activate clot formation and maintain hemostasis, platelets adhere and spread onto sites of vascular injury. Although this process is well-characterized biochemically, how the physical and spatial cues in the microenvironment affect platelet adhesion and spreading remain unclear. In this study, we applied deep UV photolithography and protein micro/nanostamping to quantitatively investigate and characterize the spatial guidance of platelet spreading at the single cell level and with nanoscale resolution. Platelets adhered to and spread only onto micropatterned collagen or fibrinogen surfaces and followed the microenvironmental geometry with high fidelity and with single micron precision. Using micropatterned lines of different widths, we determined that platelets are able to conform to micropatterned stripes as thin as 0.6 µm and adopt a maximum aspect ratio of 19 on those protein patterns. Interestingly, platelets were also able to span and spread over non-patterned regions of up to 5 µm, a length consistent with that of maximally extended filopodia. This process appears to be mediated by platelet filopodia that are sensitive to spatial cues. Finally, we observed that microenvironmental geometry directly affects platelet biology, such as the spatial organization and distribution of the platelet actin cytoskeleton. Our data demonstrate that platelet spreading is a finely-tuned and spatially-guided process in which spatial cues directly influence the biological aspects of how clot formation is regulated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026437PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197646PMC
February 2012

Mechanics and contraction dynamics of single platelets and implications for clot stiffening.

Nat Mater 2011 Jan 5;10(1):61-6. Epub 2010 Dec 5.

Department of Bioengineering, University of California, Berkeley, California 94720, USA.

Platelets interact with fibrin polymers to form blood clots at sites of vascular injury. Bulk studies have shown clots to be active materials, with platelet contraction driving the retraction and stiffening of clots. However, neither the dynamics of single-platelet contraction nor the strength and elasticity of individual platelets, both of which are important for understanding clot material properties, have been directly measured. Here we use atomic force microscopy to measure the mechanics and dynamics of single platelets. We find that platelets contract nearly instantaneously when activated by contact with fibrinogen and complete contraction within 15 min. Individual platelets can generate an average maximum contractile force of 29 nN and form adhesions stronger than 70 nN. Our measurements show that when exposed to stiffer microenvironments, platelets generated higher stall forces, which indicates that platelets may be able to contract heterogeneous clots more uniformly. The high elasticity of individual platelets, measured to be 10 kPa after contraction, combined with their high contractile forces, indicates that clots may be stiffened through direct reinforcement by platelets as well as by strain stiffening of fibrin under tension due to platelet contraction. These results show how the mechanosensitivity and mechanics of single cells can be used to dynamically alter the material properties of physiologic systems.
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http://dx.doi.org/10.1038/nmat2903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236662PMC
January 2011
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