Clinical Science
Laryngology
Treatment Outcomes in Idiopathic Subglottic Stenosis
Idiopathic subglottic stenosis is a debilitating and progressive narrowing of the trachea (windpipe) due to scar formation that results in restricted breathing and can be life threatening if left untreated. This rare condition has no known cause, but typically affects otherwise healthy Caucasian women around 50 years of age and often requires recurrent surgical procedures to restore the breathing passage over the remainder of an individual’s lifetime. The rarity of this condition (1:400,000) limits the scientific progression in understanding the cause and treatment outcomes of this orphan disease. Therefore, the goal of the project is to create an international, multi-institutional prospective cohort of iSGS patients through a sophisticated open-access data infrastructure. As a pragmatic prospective trial, it will enable rigorous treatment strategy comparisons to determine 1) how well the most commonly used treatments in iSGS work; and 2) what quality of life trade-offs are associated with each approach. This unprecedented level of research collaboration seeks to enroll the majority of patients with this rare condition throughout North America, making it the largest study of its kind by ten-fold.
Collaborators: North American Airway Collaborative (NoAAC)
Link: https://noaac.net/
Utility of Routine Spirometry Measures for Surveillance of Idopathic Subglottic Stenosis.
This study provided evidence supporting the use of peak expiratory flow (PEF) as a simple, efficient, and accessible way of monitoring progression of idiopathic subglottic stenosis and predicting receipt of surgical intervention.
Link: https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2712318
Molecular analysis of idiopathic subglottic stenosis for Mycobacterium species.
These studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention.
Link: https://www.ncbi.nlm.nih.gov/pubmed/27295947
Idiopathic subglottic stenosis is associated with activation of the inflammatory IL-17A/IL-23 axis
Our results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention.
Comorbid Dysphagia and Dyspnea in Muscle Tension Dysphonia: A Global Laryngeal Musculoskeletal Problem
Patients presenting for dysphonia who are diagnosed with muscle tension dysphonia (MTD) have a high rate of comorbid dysphagia. Patients who reported dysphagia had significantly higher self-reported voice impairment and greater severity of breathing dysfunction as measured by the Clinical COPD Questionnaire. The coincidence of these symptoms in this patient cohort may suggest an underlying pathophysiology that has yet to be elucidated. Further prospective studies are needed to clarify the underlying cause of dysphagia and breathing dysfunction in the setting of MTD and to investigate diagnostic and therapeutic paradigms.
Head and Neck Oncology
Non-HPV-Related Head and Neck Squamous Cell Carcinoma in a Young Patient Cohort
Compared to older patients, young patients who develop non-HPV-related Head and Neck Squamous Cell Carcinoma (HNSCC) tend to be more gender-balanced and are more likely to be never smokers. They have similarly aggressive disease with comparable DFS. However, they have superior overall survivorship (OS) and conditional survival after recurrence, which may be due to fewer comorbidities and thus better overall health.
Link: https://pubmed.ncbi.nlm.nih.gov/32584613/
Prognostic Value of Albumin in Patients With Head and Neck Cancer
The findings from this study suggested that in patients with head and neck cancer, lower preoperative serum albumin is associated with an increased rate of wound infection and poorer OS. The effect on OS is most pronounced in patients with upper aerodigestive squamous cell carcinoma.
Link: https://www.ncbi.nlm.nih.gov/pubmed/26864349
Salvage laryngectomy and laryngopharyngectomy: Multicenter review of outcomes associated with a reconstructive approach
In this cohort, primary closure was associated with a statistically higher fistula rate compared to vascularized tissue augmentation. The presence or absence of muscle in the reconstruction did not significantly alter the fistula rate. Vascularized tissue augmentation with muscle led to worse speech and swallowing function compared to primary closure or vascularized tissue augmentation without muscle. This finding could be due to inherent features of the pectoralis muscle donor site or it could be due to treatment selection bias by surgeons who used this donor site. Swallowing and speech were not statistically different when comparing vascularized tissue augmentation without muscle and primary closure.
Association of Preoperative Calcium and Calcitriol Therapy With Postoperative Hypocalcemia After Total Thyroidectomy
Preoperative calcium and calcitriol supplementation, in addition to routine postoperative supplementation, was associated with a reduced incidence of symptomatic hypocalcemia, length of hospital stay, and overall charges following total thyroidectomy.
Link: https://www.ncbi.nlm.nih.gov/pubmed/28418509
Preoperative vitamin D level as predictor of post‐thyroidectomy hypocalcemia in patients sustaining transient parathyroid injury
The results from this study suggest that vitamin D deficiency is a significant predictor of postoperative hypocalcemia in patients in whom ≥3 parathyroid glands are identified intraoperatively, but not in patients who sustain minimal transient damage to the parathyroid glands
Rigid Esophagoscopy for Head and Neck Cancer Staging and the Incidence of Synchronous Esophageal Malignant Neoplasms.
Rigid esophagoscopy is safe, but the utility is low for cancer staging and for detection of nonmalignant esophageal disease. Review of the literature and analysis of a large national cancer data set indicate that the incidence of synchronous esophageal malignant neoplasms in patients with head and neck squamous cell carcinoma (HNSCC) is low and has been decreasing during the past 3 decades. Thus, screening esophagoscopy should be limited to patients with HNSCC who are at high risk for synchronous esophageal malignant neoplasms.
Suprafascial Harvest of the Radial Forearm Free Flap Decreases the Risk of Postoperative Tendon Exposure
Suprafascial harvest of the radial forearm free flap (RFFF) decreases the risk of postoperative tendon exposure. The suprafascial harvest technique does not increase harvest time or donor site complications, nor does it negatively impact flap vascularity.
Beyond broadband: digital inclusion as a driver of inequities in access to rural cancer care
Although telemedicine is often highlighted as a care delivery mechanism to reduce disparities for those living in rural areas, in today’s broadband environment, its use is limited. Many rural cancer survivors who depend on their primary site of care for access to supportive care services may need to either travel to the site of care or forgo care that cannot be delivered via telephone. Expanding telemedicine to rural cancer survivors requires innovative solutions. By housing telemedicine sites within rural public libraries, statewide cancer institutions can improve care to rural survivors, while supporting what otherwise may be a fading institution, the rural public library.
Facial Plastic Surgery
Quality of Life Survey Developement in Patients Undergoing Mohs Surgery for Non-Melanoma Skin Cancers
The treatment process after diagnosis of a non-melanoma skin cancer (NMSC) involves resection of the tumor followed by reconstruction if indicated and/or desired. The new wound suffered after resection is often larger than expected by the patient and confers a significant amount of emotional distress. The purpose of this study is to measure the impact of Mohs surgery for the removal of facial squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and type of reconstruction (or lack of reconstruction) on quality of life.
Comparison of Outcomes of Early vs Delayed Graft Reconstruction of Mohs Micrographic Surgery Defects
This study found that delaying reconstruction in FTSGs and composite grafts was associated with decreased rates of postoperative complications, and male sex was associated with an increased risk of postoperative complications. The findings suggest that this strategy can be considered in patients at increased risk for developing postoperative complications, such as current smokers, patients with large defects, and patients who require use of composite grafts
Link: https://www.ncbi.nlm.nih.gov/pubmed/30422211
Association of Mohs Reconstructive Surgery Timing With Postoperative Complications
We found no association between timing of Mohs reconstructive surgery and complications, indicating that a delayed repair did not increase the risk of infection or flap failure. Variables associated with an increased risk of postoperative complications include smoking status, size of the defect, full-thickness defects, interpolated flaps with cartilage grafting, and the use of composite grafts.
Link: https://www.ncbi.nlm.nih.gov/pubmed/28880987
Dog bite injuries to the face: Is there risk with breed ownership? A systematic review with meta-analysis
Breeds vary in both rates of biting and severity. The highest risk breeds had both a high rate of biting and caused significant tissue injury. Physical characteristics can also help determine risk for unknown or mixed dog breeds. Potential dog owners can utilize this data when assessing which breed to own.
Link: https://www.ncbi.nlm.nih.gov/pubmed/30579079
Classifying and Standardizing Panfacial Trauma With a New Bony Facial Trauma Score
Facial trauma severity as measured by the bony facial trauma score (BFTS) correlated with depth of penetration of the fixed mass into the face. In this study, the BFTS was clinically relevant, had high fidelity in communicating the fractures sustained in facial trauma, and correlated well with previously validated models.
Rhinology
Quality Improvement in Chronic Rhinosinusitis
Quality improvement (QI) in CRS is garnering increasing attention. CRS is one of the most common of chronic diseases, and the management of CRS is known to have wide variability between geographic regions and providers. However, robust QI programs are rare nationwide. In conjunction with the American Rhinologic Society QI committee, the UVA Rhinology division is striving to understand the barriers to effective QI in CRS and to implement feasible solutions that promote high quality of care for all CRS patients.
A brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis
Using less than half of the questions in the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS), excellent correlations with both total and domain-specific scores are achieved. A brief version of the QOD-NS may prove useful in future clinical and research settings.
Link: https://www.ncbi.nlm.nih.gov/pubmed/31430061
Long-term outcomes of endoscopic sinus surgery in the management of adult chronic rhinosinusitis
Ten-year prospective outcomes of ESS for CRS demonstrate that the initial clinically significant improvements in QOL seen 6 months postoperatively are durable over the long term. Over 75% of patients reported clinically significant long-term QOL and HUV improvement. HUV returned to normal. Revision surgery rate was 17% and worse postoperative endoscopy scores within 18 months of initial ESS were associated with higher likelihood of revision surgery. Most patients would pursue ESS again and recommend the procedure to other patients considering this treatment option.
Link: https://www.ncbi.nlm.nih.gov/pubmed/31207172
Symptom Importance, Patient Expectations, and Satisfaction in CRS
Nasal, smell, and sleep-related symptoms were consdidered most important by this cohort. Meeting of preoperative expectations, improvement of the most important symptoms, and the magnitude of change in the SNOT-22 may drive postoperative satisfaction.
Link: https://www.ncbi.nlm.nih.gov/pubmed/30748101
Establishing the minimal clinically important difference for the Questionnaire of Olfactory Disorders
The distribution‐based minimal clinically important difference (MCID) value determinations of the Questionnaire of Olfactory Disorders Negative Statements (QOD‐NS) survey instrument range between 2.6 to 8.6 points, with an average value of 5.2. Once stratified by normal vs abnormal QOD‐NS scores at baseline, the majority of patients with abnormal preoperative QOD‐NS achieve an MCID in olfactory‐specific QOL. A better understanding of why some patients perceive improved olfactory QOL and prognostic factors is needed.
Differential Expression of Extracellular Matrix Components in Nasal Polyp Endotypes
Nasal polyp extracellular matrix composition differs with disease state with higher expression in cases where eosinophil levels are low. This suggests that in eosinophilic polyps there is a loss of matrix deposition either through break down or a failure to produce the essential components. Understanding these differences may identify new therapeutic targets.
Link: https://www.ncbi.nlm.nih.gov/pubmed/31237767
Lack of Efficacy of Symptoms and Medical History in Distinguishing the Degree of Eosinophilia in Nasal Polyps
The ability to individualize therapies for NP is dependent on identifying clinical features or biomarkers of eosinophilia. However, with the exception of circulating eosinophilia, we could not identify a clinical feature or biomarker that robustly predicted the presence of tissue eosinophilia. Even more problematic, even the seeming “criterion standard” determination of tissue pathology was of limited value, as our cohort displayed a continuous spectrum of tissue eosinophil expression, making arbitrary any definitive cutoff distinguishing these conditions.
Link: https://www.ncbi.nlm.nih.gov/pubmed/28499777
Failure of itraconazole to prevent T-helper type 2 cell immune deviation: Implications for chronic rhinosinusitis
Itraconazole did not alter the ability of naive T cells to proliferate or secrete cytokines under Th1 or Th2 deviating conditions in vitro. As such, reported inhibition of Th2-like lymphocyte function by itraconazole reflected action on mature effector cells and may have underscored why antifungal treatment failed in many clinical trials of eosinophilic chronic rhinosinusitis.
Eosinophil production of prostaglandin D2 in patients with aspirin-exacerbated respiratory disease
In addition to mast cells, eosinophils represent an important source of PGD2 in patients with AERD and identify a new target for therapeutic intervention.
Preoperative management of spontaneous cerebrospinal fluid rhinorrhea with acetazolamide
This is the first study to report the use of acetazolamide therapy as a primary treatment option for spontaneous CSF rhinorrhea. This therapy enabled surgery to be avoided in 31.3% of patients. This would indicate that in the absence of other contraindications for delaying repair, a trial of acetazolamide therapy could be considered as an initial option in the management of isolated spontaneous CSF rhinorrhea.
A Prospective Study of Outcomes of Septoplasty with Turbinate Reductions in Patients with Allergic Rhinitis
Although patients with allergic rhinitis report greater allergy-related QOL impairment (mini-RQLQ) on a day-to-day basis than nonallergic patients, this does not appear to attenuate the benefit they might experience from septoplasty and turbinate reductions when indicated for nasal obstruction. Furthermore, the symptomatic relief of their structural nasal obstruction appears to significantly improve their overall allergy-related quality of life. If appropriate expectations are set pre-operatively, allergic rhinitis is neither a contraindication nor a deterrent to septoplasty and turbinate reductions and these patients can reasonably expect a high degree of satisfaction post-operatively.
The Olfactory Cleft Endoscopy Scale: a multi-institutional validation study in chronic rhinosinusitis
The purpose of this study was to evaluate the validity of the olfactory clef endoscopy scale (OCES) instrument. This study validated the OCES as a valid olfactory-specific measure that demonstrated strong validity and provides complimentary information to traditional sinus endoscopy to aid in our understanding of OD associated with CRS.
Link: https://pubmed.ncbi.nlm.nih.gov/33006331/
Olfactory Function After Surgical Treatment of CRS: A Comparison of CRS Patients to Healthy Controls
This study was conducted to compare postoperative measures of OD in CRS patients with controls. ESS improved olfactory metrics and restored olfactory function in approximately 50% of patients with CRS to that of healthy controls. Concurrent septoplasty increased the likelihood of achieving normal olfaction, while NP and previous ESS decreased those odds.
Link: https://pubmed.ncbi.nlm.nih.gov/32954837/
Taste Impairment in Chronic Rhinosinusitis
Taste dysfunction is a common complaint in CRS. This cohort shows prevalence of gustatory loss to be about 28% using ideal normative values. This dysfunction correlated with male gender, smoking history, and older age. Taste dysfunction did not correlate with measured olfactory outcomes.
Otology and Neurotology
Clinical studies have shown that unilateral hearing loss in children is a greater disability than previously appreciated. A subset of children with unilateral hearing loss is at risk for grade retention and lower scholastic performance than children with binaural hearing. With the unique population of congenital aural atresia patients seen at UVA, we are trying to uncover the disabilities associated with unilateral hearing loss in children, identify which children are at risk for underperforming, and put in place habilitative measures that will contribute to their academic and social success.
Is There a Right Ear Advantage in Congenital Aural Atresia?
Contrary to the hypothesis that a normal hearing right ear confers a language advantage in patients with unilateral hearing loss, children with left CAA (normal right ear) were statistically more likely to be enrolled in a special education program and have behavioral problems. Reported communication problems were more common in right CAA patients, but this did not reach statistical significance. No differences were found in use of amplification, frequency modulated system, individualized education program, or grade retention. Further investigation of both the clinical implications and underlying psychoacoustics of unilateral hearing loss and the identification and habilitation of “at risk” unilateral hearing loss children is warranted.
Surgery for congenital aural atresia is a challenging operation with somewhat variable long-term hearing outcomes. We are analyzing long-term hearing outcomes and are looking at anatomic and audiologic factors that portend better hearing outcomes and better surgical candidacy for these children.
Long-term Audiometric Outcomes After Atresiaplasty for Congenital Aural Atresia
All patients enjoyed improvement in AC PTA after surgery (preoperative minus the best postoperative PTA, mean = 34 dB, range = 3.3–52 dB). Hearing declined by an average 8.2 dB over the long-term leaving a final average AC PTA of 37.4 dB HL. Sixty-four percent of patients exhibited stable (< 10 dB loss) hearing over time; 36% lost 10 dB or more over the long-term follow-up period. Hearing results typically stabilize over time with most of the change occurring in the first 3 years after CAA repair. Bone conduction thresholds remained stable over the study period.
Link: https://pubmed.ncbi.nlm.nih.gov/31821263/
Relationship Between Middle Ear Volume and Long-term Audiological Outcomes in Congenital Aural Atresia Repair
The purpose of this study was to evaluate the three-dimensional radiographic anatomy of the middle ear space among patients undergoing surgery to repair CAA and to correlate this volume with long-term hearing outcomes. The findings from this study suggest that for patients undergoing CAA repair, larger middle ear volume is associated with stable and better long-term audiometric outcomes.
Link: https://www.ncbi.nlm.nih.gov/pubmed/31135676
Semiautomated Middle Ear Volume Measurement as a Predictor of Postsurgical Outcomes for Congenital Aural Atresia.
Middle ear volume, calculated in a semiautomated fashion, is predictive of postsurgical audiometric outcomes, both independently and in combination with the conventional J-score.
Correlation between hearing loss and middle ear volume in patients with a tympanic membrane perforation.
Calculated mastoid-middle ear volume (MMEV) by segmentation analysis on CT imaging may be a more accurate estimate of MMEV than tympanometry. MMEV may be correlated to the degree of conductive hearing loss in the setting of isolated TM perforation where greater volume was associated with better hearing.
Use of Positive Airway Pressure Following Middle Ear Surgery: A Practice Survey of Otologists
This survey study found that treatment recommendations regarding postoperative PAP treatment for obstructive sleep apnea vary greatly among practicing otologists. Providers who think that an adverse outcome was attributed to PAP use were more likely to prophylactically plug the Eustachian tube during surgery. Future research will provide additional information which will allow a better understanding of the effect of PAP on the middle ear, especially after otologic surgery.
Pediatric Otolaryngology
Understanding the asthmatic response to an experimental rhinovirus infection: Exploring the effects of blocking IgE
Lower respiratory tract sympsons and blood eosinophil counts were augmented and lung function was reduced among allergic asthmatics early after rhinovirus inoculation but increased late in the infection during symptom resolution. The effect of administering omalizumab on the response to rhinovirus was most pronounced during the early/innate phase of the infection.
Link: https://pubmed.ncbi.nlm.nih.gov/32018030/
Lung Lavage Granulocyte Patterns and Clinical Phenotypes in Children with Severe, Therapy-Resistant Asthma
In children with severe, therapy-resistant asthma, BAL granulocyte patterns and infectious species are associated with novel phenotypic features that can inform pathway-specific revisions in treatment. In 32% of children evaluated, BAL revealed corticosteroid-refractory eosinophilic infiltration amenable to anti-TH2 biological therapies, and in 12%, a treatable bacterial pathogen
Sleep disordered breathing affects quality of sleep, leads to difficulties with attention and concentration, and can lead to problems with growth in children. Research studies seek to identify potential causes of pediatric sleep apnea through the study or airway anatomy and the effects of lack of sleep on thinking and concentration.
Collaborators: Stephen V. Early, M.D.; Paul Surrat, M.D.