Cryo-Fluorescence Tomography as a Tool for Visualizing Whole-Body Inflammation Using Perfluorocarbon Nanoemulsion Tracers.

PURPOSE: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging. PROCEDURES: Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths. RESULTS: PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light. CONCLUSIONS: CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology.

(VISIION-S): Viz.ai Implementation of Stroke augmented Intelligence and communications platform to improve Indicators and Outcomes for a comprehensive stroke center and Network - Sustainability.

OBJECTIVES: As Comprehensive Stroke Centers (CSCs) strive to improve neuro-intervention (NIR) times, process improvements are put in place to streamline workflows. Our prior publication (VISIION) demonstrated improvements in key performance indicators (KPIs). The purpose VISIION-S was to analyze whether those results were sustainable. MATERIALS AND METHODS: Consecutive Direct Arriving LVO (DALVO) and telemedicine transfer LVO (BEMI) stroke NIR cases were assessed, including subgroups of DALVO-OnHours, DALVO-OffHours, BEMI-OnHours, and BEMI-OffHours. We analyzed times for the original 6 months pre (6/10/20-1/15/21) and compared them to a 17 month post-implementation period (1/16/21- 6/25/22) to evaluate for sustainability. Mann-Whitney U was utilized. RESULTS: 150 NIR cases were analyzed pre (n = 47) v. post (n = 103) implementation (DALVO-OnHours 7 v. 20, DALVO-OffHours 10 v. 25, BEMI-OnHours 13 v. 20, BEMI-OffHours 17 v. 38). For Door-to-groin (DTG), improvement was noted for DALVO-OffHours 39%(157 min,96 min;p < 0.001), DALVO-ALL 25%(127 min,95 min;p = 0.006), BEMI-OffHours 46%(45 min,25 min;p = 0.023), and BEMI-ALL 40%(42 min,25 min;p = 0.005). Activation-to-groin (ATG), door-to-device (DTD), and door-to-recanalization (DTR) also showed statistical improvements. For DALVO-OffHours, there were reductions in door to CT (DTC) 80%(26 min,5 min;p < 0.001), ATG 32%(90 min,61 min;p = 0.036), DTG 39%(157 min,96 min;p < 0.001), DTD 31%(178 min,123 min;p = 0.002), and DTR 32%(197 min,135 min;p = 0.003). CONCLUSIONS: We noted sustainability over a 17 month period with sustained reduction in KPIs for even more NIR time interval comparisons. In the greatest opportunity subgroup (DALVO-OffHours), we noted a reduction in all 5 time interval metrics. Our sustainability finding is important to show that process improvements continued even after the immediate period, adding credibility to the results. Models such as this could be useful for other centers striving to optimize workflow and improve times.

Method for estimation of apoptotic cell fraction of cytotherapy using in vivo fluorine-19 magnetic resonance: pilot study in a patient with head and neck carcinoma receiving tumor-infiltrating lymphocytes labeled with perfluorocarbon nanoemulsion.

BACKGROUND: Adoptive transfer of T cells is a burgeoning cancer therapeutic approach. However, the fate of the cells, once transferred, is most often unknown. We describe the first clinical experience with a non-invasive biomarker to assay the apoptotic cell fraction (ACF) after cell therapy infusion, tested in the setting of head and neck squamous cell carcinoma (HNSCC). A patient with HNSCC received autologous tumor-infiltrating lymphocytes (TILs) labeled with a perfluorocarbon (PFC) nanoemulsion cell tracer. Nanoemulsion, released from apoptotic cells, clears through the reticuloendothelial system, particularly the Kupffer cells of the liver, and fluorine-19 (19F) magnetic resonance spectroscopy (MRS) of the liver was used to non-invasively infer the ACF. METHODS: Autologous TILs were isolated from a patient in their late 50s with relapsed, refractory human papillomavirus-mediated squamous cell carcinoma of the right tonsil, metastatic to the lung. A lung metastasis was resected for T cell harvest and expansion using a rapid expansion protocol. The expanded TILs were intracellularly labeled with PFC nanoemulsion tracer by coincubation in the final 24 hours of culture, followed by a wash step. At 22 days after intravenous infusion of TILs, quantitative single-voxel liver 19F MRS was performed in vivo using a 3T MRI system. From these data, we model the apparent ACF of the initial cell inoculant. RESULTS: We show that it is feasible to PFC-label ~70×1010 TILs (F-TILs) in a single batch in a clinical cell processing facility, while maintaining >90% cell viability and standard flow cytometry-based release criteria for phenotype and function. Based on quantitative in vivo 19F MRS measurements in the liver, we estimate that ~30% cell equivalents of adoptively transferred F-TILs have become apoptotic by 22 days post-transfer. CONCLUSIONS: Survival of the primary cell therapy product is likely to vary per patient. A non-invasive assay of ACF over time could potentially provide insight into the mechanisms of response and non-response, informing future clinical studies. This information may be useful to developers of cytotherapies and clinicians as it opens an avenue to quantify cellular product survival and engraftment.

B3 thymoma mimicking poorly differentiated thyroid carcinoma: Diagnostic pitfalls of anterior mediastinal mass fine needle aspiration.

B3 thymoma is a rare malignant type of thymic epithelial neoplasm found in the anterior mediastinum. Diagnosis of thymoma from fine needle aspiration (FNA) can be challenging due to the infrequency of sampling and its morphologic overlap with other entities such as squamous cell carcinoma, lymphoma or thyroid carcinoma. We report a case of B3 thymoma mimicking poorly differentiated thyroid carcinoma. We present its diagnostic pitfalls on cytology specimens, especially where it concerns identifying the correct location of the lesion, discuss the differential diagnosis, and correlation with the corresponding surgical resection specimen. A neck computed tomography angiogram (CTA) revealed a partially calcified 2.1 cm mass inferior to the left thyroid lobe in a 51 yr old woman being evaluated for stroke/TIA symptoms. She was referred for evaluation of the lesion. On the initial FNA and core needle biopsy, the lesion showed high-grade epithelioid cells with abundant lymphocytic infiltration and occasional necrosis, and was diagnosed as a high-grade carcinoma, favored to represent a poorly differentiated thyroid carcinoma considering the location on imaging. The patient subsequently underwent total thyroidectomy, central neck dissection, and thymectomy. Final surgical pathologic diagnosis indicated a type B3 thymoma. Due to the infrequency of sampling, thymoma poses a diagnostic challenge on preoperative FNA or core needle biopsy. Herein, we present a case of B3 thymoma with a preoperative cytologic specimen that consisted of hyperchromatic sheets of epithelioid tumor cells with a background of lymphocytes without definitive follicular cells or colloid. The core needle biopsy and cell block material showed abundant necrosis, intermixed lymphocytes and neoplastic epithelial cells with strong positive staining for pan-keratin and p40. The cytology and core needle biopsy material were interpreted as representing a probable thyroid neoplasm and raised a broad differential including anaplastic thyroid carcinoma, poorly differentiated thyroid carcinoma with squamous features, metastatic squamous carcinoma, and metastatic carcinoma to a lymph node. The final surgical resection specimen showed a B3 type-thymoma.

A phase I study of avelumab, palbociclib, and cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma.

OBJECTIVES: We aimed to test the safety of the CDK4/6 inhibitor palbociclib in combination with the EGFR inhibitor cetuximab and the PD-L1 inhibitor avelumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). MATERIALS AND METHODS: This phase I study enrolled eligible adult patients with R/M HNSCC into three sequential single dose-escalation cohorts of palbociclib (75, 100, and 125 mg) PO daily on days 1 to 21 of a 28-day cycle in combination with avelumab 10 mg/kg IV every 2 weeks and cetuximab 400 mg/m2IV on day 1, then 250 mg/m2weekly thereafter. The study followed a 3 + 3 design with no intra-patient escalation. The primary objective was to identify the recommended phase II dose (RP2D); secondary objectives included overall response rate (ORR), duration of response (DOR), progression free survival (PFS), and overall survival (OS). RESULTS: Palbociclib in combination with avelumab and cetuximab was well tolerated, with rash and fatigue being the most common adverse events. A single dose-limiting toxicity was observed at the 125 mg dose of palbociclib: a grade 3 infusion reaction related to cetuximab. The RP2D of palbociclib is 125 mg, with avelumab and cetuximab at standard doses. The ORR by RECIST v1.1 was 42 %, the median DOR and OS have not been reached. Median PFS was 6.5 months. CONCLUSIONS: The combination of avelumab, cetuximab, and palbociclib was well tolerated and supports further evaluation in patients with R/M HNSCC. CLINICAL TRIAL REGISTRATION NUMBER: NCT03498378.

Inappropriate requesting of parathyroid scintigraphy at an academic medical center.

BACKGROUND: Primary hyperparathyroidism is a biochemical, not radiologic diagnosis. Parathyroid scintigraphy should only be requested for surgical planning, not to confirm diagnosis. Here we determined reasons for inappropriately ordered parathyroid scintigraphy. METHODS: We generated a database of patients undergoing parathyroid scintigraphy over 5 years, who did not undergo parathyroidectomy. RESULTS: Over 5 years 129 parathyroid scintigraphies (of 308 total scans) were performed in patients who did not undergo parathyroidectomy. We determined that only 58 (45%) had true primary hyperparathyroidism. The most common reason for the scan was to "confirm the diagnosis." Only 20% were ordered for adenoma localization, although surgery was not performed. Physicians requesting parathyroid scintigraphies specialized in a variety of disciplines. CONCLUSION: Forty-two percent of parathyroid scintigraphies were requested inappropriately to "confirm" a diagnosis of primary hyperparathyroidism. We propose to change the ordering system to clarify that parathyroid scintigraphy is a functional tool to optimize surgery when the diagnosis is secure.

Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial.

BACKGROUND: Pembrolizumab (PD-1 inhibitor) and cetuximab (EGFR inhibitor) are active as single agents and in combination with cytotoxic chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Given each drug's single agent activity and unique mechanism of action, we aimed to evaluate the anti-tumour activity of PD-1 blockade with EGFR inhibition in recurrent or metastatic HNSCC. METHODS: This study is an open-label, non-randomised, multi-arm, phase 2 trial done at four academic centres in the USA. Participants were required to have platinum-resistant or platinum-ineligible, recurrent or metastatic HNSCC, be at least 18 years old, have an Eastern Cooperative Oncology Group performance status 0-1, have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and to have received no previous immunotherapy or EGFR inhibition. All participants received pembrolizumab 200 mg intravenously every 3 weeks, combined with an initial loading dose of cetuximab 400 mg/m2 intravenously followed by 250 mg/m2 intravenously weekly (21 day cycle). The primary endpoint was overall response rate defined as the proportion of participants with a partial or complete responses (per RECIST version 1.1) by 6 months in the intention-to-treat population. The safety population included all participants who received at least one dose of pembrolizumab. Herein, the final analysis of cohort 1 (no previous PD-1, PD-L1, or EGFR inhibition for recurrent or metastatic HNSCC) is reported. Three additional cohorts (two for participants with a previous response to immunotherapy followed by relapse or progression, with or without previous cetuximab exposure, and one for cutaneous HNSCC) will be reported separately once fully accrued. This study is registered with ClinicalTrials.gov, NCT03082534, and remains open as the three additional cohorts are actively accruing participants. FINDINGS: Between March 22, 2017, and July 16, 2019, 33 participants were enrolled to cohort 1. All 33 participants received at least one dose of pembrolizumab. Median follow-up duration was 7·3 months (IQR 3·9-10·9). By 6 months, the overall response rate was 45% (95% CI 28-62), with 15 of 33 participants achieving a partial response. The most common grade 3-4 treatment-related adverse event was oral mucositis (three [9%] of 33 participants), and serious treatment-related adverse events occurred in five (15%) participants. No treatment-related deaths occurred. INTERPRETATION: Pembrolizumab combined with cetuximab shows promising clinical activity for recurrent or metastatic HNSCC, and merits further investigation. FUNDING: Merck Sharp & Dohme.

ACR Appropriateness Criteria® Syncope.

Syncope and presyncope lead to well over one million emergency room visits in the United States each year. Elucidating the cause of syncope or presyncope, which are grouped together given similar etiologies and outcomes, can be exceedingly difficult given the diverse etiologies. This becomes more challenging as some causes, such as vasovagal syncope, are relatively innocuous while others, such as cardiac-related syncope, carry a significant increased risk of death. While the mainstay of syncope and presyncope assessment is a detailed history and physical examination, imaging can play a role in certain situations. In patients where a cardiovascular etiology is suspected based on the appropriate history, physical examination, and ECG findings, resting transthoracic echocardiography is usually considered appropriate for the initial imaging. While no imaging studies are considered usually appropriate when there is a low probability of cardiac or neurologic pathology, chest radiography may be appropriate in certain clinical situations. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR appropriateness criteria syncope

Syncope and presyncope lead to well over one million emergency room visits in the United States each year. Elucidating the cause of syncope or presyncope, which are grouped together given similar etiologies and outcomes, can be exceedingly difficult given the diverse etiologies. This becomes more challenging as some causes, such as vasovagal syncope, are relatively innocuous while others, such as cardiac-related syncope, carry a significant increased risk of death. While the mainstay of syncope and presyncope assessment is a detailed history and physical examination, imaging can play a role in certain situations. In patients where a cardiovascular etiology is suspected based on the appropriate history, physical examination, and ECG findings, resting transthoracic echocardiography is usually considered appropriate for the initial imaging. While no imaging studies are considered usually appropriate when there is a low probability of cardiac or neurologic pathology, chest radiography may be appropriate in certain clinical situations. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study.

PURPOSE: Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. PATIENTS AND METHODS: Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS). RESULTS: The study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m2. EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively. CONCLUSION: Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.

ACR Appropriateness Criteria® Dementia.

Degenerative disease of the central nervous system is a growing public health concern. The primary role of neuroimaging in the workup of patients with probable or possible Alzheimer disease has typically been to exclude other significant intracranial abnormalities. In general, the imaging findings in structural studies, such as MRI, are nonspecific and have limited potential in differentiating different types of dementia. Advanced imaging methods are not routinely used in community or general practices for the diagnosis or differentiation of forms of dementia. Nonetheless, in patients who have been evaluated by a dementia expert, FDG-PET helps to distinguish Alzheimer disease from frontotemporal dementia. In patients with suspected dementia with Lewy bodies, functional imaging of the dopamine transporter (ioflupane) using SPECT may be helpful. In patients with suspected normal-pressure hydrocephalus, DTPA cisternography and HMPAO SPECT/CT brain may provide assessment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Movement Disorders and Neurodegenerative Diseases.

Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult due to the variable features of these conditions, unusual clinical presentations, and overlapping symptoms and characteristics. MRI has an important role in the initial assessment of these patients, although a combination of imaging and laboratory and genetic tests is often needed for complete evaluation and management. This document summarizes the imaging appropriateness data for rapidly progressive dementia, chorea, Parkinsonian syndromes, suspected neurodegeneration with brain iron accumulation, and suspected motor neuron disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Thoracic Outlet Syndrome.

Thoracic outlet syndrome (TOS) is the clinical entity that occurs with compression of the brachial plexus, subclavian artery, and/or subclavian vein at the superior thoracic outlet. Compression of each of these structures results in characteristic symptoms divided into three variants: neurogenic TOS, venous TOS, and arterial TOS, each arising from the specific structure that is compressed. The constellation of symptoms in each patient may vary, and patients may have more than one symptom simultaneously. Understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes is important in choosing and interpreting radiological imaging performed to help diagnose TOS and plan for intervention. This publication has separated imaging appropriateness based on neurogenic, venous, or arterial symptoms, acknowledging that some patients may present with combined symptoms that may require more than one study to fully resolve. Additionally, in the postoperative setting, new symptoms may arise altering the need for specific imaging as compared to preoperative evaluation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Clinical Practice Guideline: Ménière's Disease.

OBJECTIVE: Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid (endolymph) volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Conventional imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many and typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies. PURPOSE: The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

Clinical Practice Guideline: Ménière's Disease Executive Summary.

OBJECTIVE: Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many, and approaches typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies. PURPOSE: The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.