Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction.

OBJECTIVE: To evaluate the efficacy and safety of intranasal theophylline saline irrigation on olfactory recovery in patients with post-viral olfactory dysfunction (PVOD). METHODS: Between May 2019 and April 2020, we conducted a double-blinded, placebo-controlled randomized clinical trial of adults with 6-36 months of PVOD. Patients were randomized to nasal theophylline saline irrigation or placebo saline irrigation twice a day for 6 weeks. The primary outcome was the Global Rating of Smell Change. Secondary outcomes were changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). RESULTS: Twenty-two patients (n = 12, theophylline; n = 10, placebo) completed the study. Slightly more patients in the theophylline group (33%) reported improved smell compared to the placebo group (30%, difference 3.3%, 95% CI -35.6% to 42.3%). The median differences in pre- and post-treatment UPSIT and QOD-NS change between the two groups were 1 (95% CI -3 to 5) and -10 (95% CI -15 to -4), respectively in favor of theophylline. Three patients receiving theophylline and 2 receiving placebo had clinically meaningful improvements on the UPSIT (difference 5%, 95% CI -30% to 40%). There were no adverse events, and serum theophylline levels were undetectable in 10/10 patients. CONCLUSIONS: While safe, there were no clinically meaningful differences in olfactory change between the two groups except for olfaction-related quality of life, which was better with theophylline. The imprecise estimates suggest future trials will need substantially larger sample sizes or treatment modifications, such as increasing the theophylline dose, to observe larger treatment effects.

Increased Bone Morphogenetic Protein Signaling in the Cutaneous Vasculature of Patients with Calciphylaxis.

BACKGROUND: The objective of this study was to investigate the role of bone morphogenetic protein (BMP) signal transduction in the pathogenesis of calciphylaxis. METHODS: Skin biopsy specimens were obtained from 18 patients with, and 12 patients without, calciphylaxis. Tissue sections were stained with antibodies directed against BMP effector proteins phosphorylated-SMAD (p-SMAD) 1/5/9, inhibitor of DNA 1 (Id1), inhibitor of DNA 3 (Id3), and Runx2. The intensity of staining was scored semi-quantitatively as strong versus weak or absent. RESULTS: Of the 18 patients with calciphylaxis (mean age: 59 ± 8 years), 9 were women and 15 had end-stage renal disease. Of the 12 control patients (mean age: 57 ± 10 years), 8 were women and 8 had end-stage renal disease. Strong staining for p-SMAD 1/5/9 was detected in blood vessels from all calciphylaxis patients. In 1 patient with calciphylaxis, strong staining for p-SMAD 1/5/9 was detected in a blood vessel that did not have evidence of calcification. Id1 and Id3 immunoreactivity was detected in blood vessels from all 12 patients with calciphylaxis that were tested. Runx2 staining was detected in all 6 patients with calciphylaxis who were tested. p-SMAD 1/5/9 immunoreactivity was weak or absent in blood vessels of 10 of the 12 control samples. CONCLUSIONS: The BMP signal transduction pathway is activated in the cutaneous vasculature of calciphylaxis patients. The ability to detect p-SMAD 1/5/9, Id1, and Id3 in cutaneous vasculature may assist in the diagnosis of calciphylaxis. As BMP signaling inhibitors become available, this pathway may serve as a future therapeutic target for calciphylaxis.

S-Nitrosylation of Calcium-Handling Proteins in Cardiac Adrenergic Signaling and Hypertrophy.

RATIONALE: The regulation of calcium (Ca(2+)) homeostasis by ß-adrenergic receptor (ßAR) activation provides the essential underpinnings of sympathetic regulation of myocardial function, as well as a basis for understanding molecular events that result in hypertrophic signaling and heart failure. Sympathetic stimulation of the ßAR not only induces protein phosphorylation but also activates nitric oxide-dependent signaling, which modulates cardiac contractility. Nonetheless, the role of nitric oxide in ßAR-dependent regulation of Ca(2+) handling has not yet been explicated fully. OBJECTIVE: To elucidate the role of protein S-nitrosylation, a major transducer of nitric oxide bioactivity, on ßAR-dependent alterations in cardiomyocyte Ca(2+) handling and hypertrophy. METHODS AND RESULTS: Using transgenic mice to titrate the levels of protein S-nitrosylation, we uncovered major roles for protein S-nitrosylation, in general, and for phospholamban and cardiac troponin C S-nitrosylation, in particular, in ßAR-dependent regulation of Ca(2+) homeostasis. Notably, S-nitrosylation of phospholamban consequent upon ßAR stimulation is necessary for the inhibitory pentamerization of phospholamban, which activates sarcoplasmic reticulum Ca(2+)-ATPase and increases cytosolic Ca(2+) transients. Coincident S-nitrosylation of cardiac troponin C decreases myocardial sensitivity to Ca(2+). During chronic adrenergic stimulation, global reductions in cellular S-nitrosylation mitigate hypertrophic signaling resulting from Ca(2+) overload. CONCLUSIONS: S-Nitrosylation operates in concert with phosphorylation to regulate many cardiac Ca(2+)-handling proteins, including phospholamban and cardiac troponin C, thereby playing an essential and previously unrecognized role in cardiac Ca(2+) homeostasis. Manipulation of the S-nitrosylation level may prove therapeutic in heart failure.

Endodermal Cyst of the Third Nerve in a Child.

Endodermal cysts, also known as neurogenic, neuroenteric, foregut, bronchogenic, respiratory, epithelial, teratomatous, or gastrocytoma cysts, can be found in the central nervous system, predominantly in the subarachnoid space of the cervical and thoracic spinal cord. We describe a child with an endodermal cyst of the third nerve and highlight neuroimaging findings, pathological correlation, clinical course, and patient management.

Temporary Lumbar Drain as Treatment for Pediatric Fulminant Idiopathic Intracranial Hypertension.

Fulminant idiopathic intracranial hypertension (FIIH) is a subtype of idiopathic intracranial hypertension (IIH) characterized by rapid, severe, progressive vision loss. Surgical intervention is often performed either as a cerebrospinal fluid (CSF) shunt procedure or an optic nerve sheath fenestration or, at times, both. These surgical procedures carry a significant risk of morbidity and failure. We present 2 patients in whom a temporary lumbar drain was successfully used in the management of medically undertreated pediatric FIIH, and circumvented the need for surgical intervention.

Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition.

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-ß (TGF-ß) family signalling pathway. Similar to TGF-ß, the complex roles of BMPs in development and disease are demonstrated by their dichotomous roles in various cancers and cancer stages. Although early studies implicated BMP signalling in tumour suppressive phenotypes, the results of more recent experiments recognize BMPs as potent tumour promoters. Many of these complexities are becoming illuminated by understanding the role of BMPs in their contextual role in unique cell types of cancer and the impact of their surrounding tumour microenvironment. Here we review the emerging roles of BMP signalling in cancer, with a focus on the molecular underpinnings of BMP signalling in individual cancers as a valid therapeutic target for cancer prevention and treatment.

Expanding the genetic and phenotypic spectrum of popliteal pterygium disorders.

The popliteal pterygia syndromes are a distinct subset of the hundreds of Mendelian orofacial clefting syndromes. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. Heterozygous mutations in IRF6 cause popliteal pterygium syndrome (PPS) while homozygous mutations in RIPK4 or CHUK (IKKA) cause the more severe Bartsocas-Papas syndrome (BPS) and Cocoon syndrome, respectively. In this study, we report mutations in six pedigrees with children affected with PPS or BPS. Using a combination of Sanger and exome sequencing, we report the first case of an autosomal recessive popliteal pterygium syndrome caused by homozygous mutation of IRF6 and the first case of uniparental disomy of chromosome 21 leading to a recessive disorder. We also demonstrate that mutations in RIPK4 can cause features with a range of severity along the PPS-BPS spectrum and that mutations in IKKA can cause a range of features along the BPS-Cocoon spectrum. Our findings have clinical implications for genetic counseling of families with pterygia syndromes and further implicate IRF6, RIPK4, and CHUK (IKKA) in potentially interconnected pathways governing epidermal and craniofacial development.

Quality of Life for Patients with Sporadic Small Vestibular Schwannomas Following Middle Fossa Craniotomy.

OBJECTIVE: To evaluate quality-of-life outcomes for patients with vestibular schwannomas (VS) undergoing a middle cranial fossa (MCF) approach. STUDY DESIGN: Prospective study from 2018 to 2023. SETTING: Tertiary academic institution. PATIENTS: Adults with sporadic VS. INTERVENTIONS: MCF. MAIN OUTCOME MEASURES: The primary outcome measure was the change in preoperative and 1-year postoperative Penn Acoustic Neuroma Quality-of-life (PANQOL) scores. Secondary outcome measures included hearing preservation and facial nerve function. RESULTS: Of the 164 patients who underwent MCF for sporadic VS, 78 patients elected to voluntarily complete preoperative PANQOL assessments prior to surgery. Seventy-one (91%) of those 78 patients completed postoperative PANQOL surveys. Fifty (70%) of the respondents were female and the median age was 48 years (range, 27-71 years). Overall, at 1-year postsurgery, a minimal clinically important difference (MCID) was obtained in the hearing (mean difference, 10.5; 95% confidence interval [CI], 4.3-16.7) and anxiety (mean difference, 18.8; 95% CI, 11.7-25.9) domains. For patients with hearing preservation (n = 48, 68%), MCIDs were reached in the hearing (mean difference, 13.4; 95% CI, 6.3-20.6), anxiety (mean difference, 20.8; 95% CI, 11.8-29.9), energy (mean difference, 13.7; 95% CI, 3.6-23.8), pain (mean difference, 13.7; 95% CI, 3.6-23.8) domains, and overall PANQOL scores (mean difference, 12.7; 95% CI, 7.1-18.3). Postoperatively, 64 (90%) patients maintained a House-Brackmann I. CONCLUSIONS: To our knowledge, this is the largest study examining disease-specific QOL for VS patients undergoing MCF. Based on our institution's experience, MCF approach for small VS is associated with clinically meaningful improvements in QOL, hearing preservation, and excellent facial nerve outcomes.

High economic burden of caring for patients with suspected extraesophageal reflux.

OBJECTIVES: Extraesophageal symptoms are common manifestations of gastroesophageal reflux disease (GERD). Lack of a definitive diagnostic or treatment standards complicate management, which often leads to multiple specialty consultations, procedures, pharmaceuticals and diagnostic tests. The aim of this study was to determine the economic burden associated with extraesophageal reflux (EER). METHODS: Direct costs of evaluation were estimated for patients referred with symptoms attributed to EER between 2007 and 2011. Medicare payment for evaluation and management and pharmaceutical prices was used to calculate first year and overall costs of evaluating and treating extraesophageal symptoms attributed to reflux. RESULTS: Overall, 281 patients were studied (cough (50%), hoarseness (23%), globus/post-nasal drainage (15%), asthma (9%), and sore throat (3%)). Over a median (interquartile range) of 32 (16-46) months follow-up, patients had a mean (95% confidence interval) of 10.1 (9.4-10.9) consultations with specialists and underwent 6.4 (3-9) diagnostic procedures. Overall, the mean initial year direct cost was $5,438 per patient being evaluated for EER. Medical and non-medical components contributed $5,154 and $283. Of the overall cost, 52% were attributable to the use of proton pump inhibitors. During the initial year, direct costs were 5.6 times higher than those reported for typical GERD ($971). A total of 54% of patients reported improvement of symptoms. Overall cost per improved patient was $13,700. CONCLUSIONS: EER contributes substantially to health-care expenditures. In this cohort, the cost for initial year's evaluation and treatment of EER symptoms was quintuple that of typical GERD. Prescription costs and, in particular, proton pump inhibitors were the single greatest contributor to the cost of EER management.

Management of Neurofibromatosis Type 2-Associated Vestibular Schwannomas.

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by a mutation in the NF2 suppressor gene and is characterized by the development of multiple benign tumors throughout the central nervous system. Bilateral vestibular schwannomas (VSs) are pathognomonic for NF2 and are associated with progressive hearing loss and eventual deafness in most patients. This review presents current management options for NF-2-associated VSs.

Early Hearing Preservation Outcomes Following Cochlear Implantation With New Slim Lateral Wall Electrode Using Electrocochleography.

OBJECTIVE: Describe early hearing preservation (HP) cochlear implantation (CI) outcomes using a new slim lateral wall electrode (SLWE). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: Adult CI candidates with preoperative low-frequency pure-tone average (LFPTA; 125, 250, 500 Hz) ≤60 dB HL. INTERVENTION: CI with and without intracochlear real-time electrocochleography (RT-ECochG). MAIN OUTCOME MEASURE: HP (LFPTA ≤80 dB HL), LFPTA shift, speech-perception performance measures, postoperative CT reconstruction. RESULTS: Forty-two subjects were implanted with the SLWE. Thirty patients underwent full insertion without RT-ECochG feedback, and HP was maintained at 3-months postactivation for 7 (23.3%) patients with mean LFPTA shift of 57.5 ±â€Š25.6 dB HL. RT-ECochG feedback was utilized on 12 patients, of whom 6 patients had full insertions and 6 patients had anywhere from 1 to 3 electrodes left outside of the cochlea based on RT-ECochG feedback. At 3 months postoperatively, HP was achieved on 10 (83.3%) patients and mean LFPTA shift was 18.9 c 11.7 dB HL. Mean difference between LFPTA threshold shift at 3-months postactivation with and without RT-ECochG was 38.6 dB HL (95% CI, 25.6-51.67). There was an improvement in delta CNC from preoperative to 3-months postactivation when using RT-ECochG, with mean difference 20.7% (95% CI, 3.3-38.1). CONCLUSIONS: Use of RT-ECochG monitoring during SLWE placement results in fewer full electrode insertions and significantly better HP rates and speech-perception outcomes when compared with unmonitored insertions. Further investigation is needed to evaluate long-term audiologic outcomes to better understand the relationships among ECochG, cochlear trauma, functional outcomes, and HP.

Development and Psychometric Validation of the Olfactory Dysfunction Outcomes Rating.

Importance: Olfactory dysfunction (OD) is an increasingly common and morbid condition, especially given the ongoing COVID-19 pandemic. Thus, the ability to reproducibly measure smell loss-associated quality of life (QOL) and its response to treatment is paramount. Objective: To develop and validate a concise and visually appealing smell loss-associated QOL patient-reported outcome measure for OD. Design, Setting, and Participants: A secondary analysis of comments to an online survey by 1000 patients with olfactory dysfunction published in 2013 was used as the primary source to generate items of the Olfactory Dysfunction Outcomes Rating (ODOR). In addition, 30 patients with OD enrolled in 2 clinical studies at a tertiary care medical center (Washington University) were asked to identify their main concerns associated with smell loss. And finally, 4 otolaryngologists reviewed the items generated from the online survey and the patients' interviews to identify any additional items. Prospective study design was used for data collection from the 30 patients and 4 otolaryngologists. Prospective study design was used for survey validation. Validation of the ODOR was performed with 283 patients enrolled in several prospective studies at a single institution that completed the ODOR as an outcome measure. Main Outcomes and Measures: Item generation and selection were the outcomes of ODOR development. The psychometric and clinimetric measures evaluated for validation were internal consistency, test-retest reliability, face and content validity, concurrent validity, and discriminant validity. Minimal clinically important difference was also determined. Results: The ODOR is a 28-item instrument with each item scored as either no difficulty or very rarely bothered (0) to complete difficulty or very frequently bothered (4) with a total instrument score range of 0 to 112 points. Higher scores indicate higher degree of dysfunction and limitation. Validation in the cohort of 283 patients (mean [SD] age, 47.0 [14.4] years; 198 female participants [73%]; 179 White participants [80%]) revealed that the instrument has high internal consistency (Cronbach α = 0.968), test-retest reliability (r = 0.90 [95% CI, 0.81-0.95]), face validity, content validity, concurrent validity (r = 0.87 [95% CI, 0.80-0.91] compared with the Questionnaire of Olfactory Disorders-Negative Statements; ρ = -0.76 [95% CI, -0.81 to -0.71] compared with a patient-reported symptom severity scale), and divergent validity (mean score difference, -33.9 [95% CI, -38.3 to -29.6] between normosmic patients and hyposmic/anosmic patients). The minimal clinically important difference was 15 points. The estimated time for survey completion was approximately 5 minutes. Conclusions and Relevance: In this survey creation and validation study, the ODOR was shown to be a novel, concise, reliable, and valid patient-reported outcome measure of OD-associated QOL. It can be used to measure physical problems, functional limitations, and emotional consequences associated with OD and how they change after a given intervention, which is clinically applicable and particularly pertinent given the growing burden of OD associated with COVID-19.

Use of Off-Label Nasal Steroid Irrigations in Long-Term Management of Chronic Rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is an inflammatory disease of the paranasal sinuses and mucosa. Topical nasal corticosteroids are a mainstay treatment for CRS by reducing sinonasal inflammation and improving mucociliary clearance. However, topical corticosteroids have limited paranasal distribution, and patient response to treatment has been variable in randomized controlled trials (RCT). Thus, there is significant interest in evaluating the efficacy of nasal steroids delivered by nasal irrigation in order to improve penetration and absorption of topical steroids into the sinonasal mucosa. In this review, we discuss the use of off-label nasal steroid irrigations in the management of CRS. METHODS: A review of clinical trials evaluating the use of nasal steroid irrigations for CRS in the PubMed electronic database was performed. RESULTS: Of the 12 clinical studies identified, 10 evaluated budesonide irrigations while the remaining 2 focused on mometasone. The overwhelming majority of studies for both budesonide and mometasone supported the use of nasal irrigations with corticosteroids over nasal corticosteroid sprays alone. However, the heterogeneity in study design, patient cohort, and volume of steroid irrigation limit the interpretations of these studies. CONCLUSIONS: Nasal irrigation with corticosteroids is beneficial and safe for the treatment of CRS. Future RCTs controlling for type of surgical intervention, CRS pheno- and endo-type, as well as dosing and duration of nasal corticosteroid irrigations are warranted.

Computed Tomography as a Predictor of Sinonasal Inverted Papilloma Origin, Skull Base Involvement, and Stage.

Objective To investigate the diagnostic performance of computed tomography (CT) to determine the origin, skull base involvement, and stage of sinonasal inverted papilloma (IP). Design This is a retrospective cohort study. Setting This is set at a tertiary care medical center. Participants Patients with preoperative CT imaging who underwent extirpative surgery for histologically confirmed sinonasal IP between January 2005 and October 2019. Main Outcome Measures The likely sites of tumor origin, skull base involvement, and radiographic tumor stage were determined by two board-certified neuroradiologists after re-reviewing preoperative CT imaging. These radiologic findings were then compared with intraoperative and pathologic findings. Results Of 86 patients, 74% (64/86) had IP lesions with correctly classified sites of origin on CT. CT was not sensitive for diagnosing ethmoid sinus origin (48%, 52%), frontal sinus origin (80%, 40%), and skull base origin (17%, 17%). CT was not sensitive (62%, 57%) but specific (86%, 98%) for identifying any skull base involvement. There was substantial-to-near perfect agreement between radiographic and pathologic Cannady stages (weighted κ = 0.61 for rater 1; weighted κ = 0.81 for rater 2). Interrater agreement was substantial for identifying tumor origin (κ = 0.75) and stage (weighted κ = 0.62) and moderate for identifying skull base involvement (κ = 0.43). Conclusion Interrater agreement on CT findings was substantial except on skull base involvement. CT correctly predicted site of tumor origin in up to 74% of subjects. CT was not sensitive for diagnosing skull base involvement but had substantial-to-near perfect agreement with pathologic tumor staging. CT is a useful but albeit limited adjunct for tumor localization and surgical planning for sinonasal IP.

Association of Olfactory Training With Neural Connectivity in Adults With Postviral Olfactory Dysfunction.

Importance: Viral upper respiratory tract infections are a major cause of olfactory loss. Olfactory training (OT) is a promising intervention for smell restoration; however, a mechanistic understanding of the changes in neural plasticity induced by OT is absent. Objective: To evaluate functional brain connectivity in adults with postviral olfactory dysfunction (PVOD) before and after OT using resting-state functional magnetic resonance imaging. Design, Setting, and Participants: This prospective cohort study, conducted from September 1, 2017, to November 30, 2019, recruited adults with clinically diagnosed or self-reported PVOD of 3 months or longer. Baseline olfaction was measured using the University of Pennsylvania Smell Identification Test (UPSIT) and the Sniffin' Sticks test. Analysis was performed between December 1, 2020, and July 1, 2020. Interventions: Participants completed 12 weeks of OT using 4 essential oils: rose, eucalyptus, lemon, and clove. The resting-state functional magnetic resonance imaging measurements were obtained before and after intervention. Main Outcome and Measures: The primary outcome measure was the change in functional brain connectivity before and after OT. Secondary outcome measures included changes in UPSIT and Sniffin' Sticks test scores, as well as patient-reported changes in treatment response as measured by subjective changes in smell and quality-of-life measures. Results: A total of 16 participants with PVOD (11 female [69%] and 14 White [88%]; mean [SD] age, 60.0 [10.5] years; median duration of smell loss, 12 months [range, 3-240 months]) and 20 control participants (15 [75%] female; 17 [85%] White; mean [SD] age, 55.0 [9.2] years; median UPSIT score, 37 [range, 34-39]) completed the study. At baseline, participants had increased connectivity within the visual cortex when compared with normosmic control participants, a connection that subsequently decreased after OT. Furthermore, 4 other network connectivity values were observed to change after OT, including an increase in connectivity between the left parietal occipital junction, a region of interest associated with olfactory processing, and the cerebellum. Conclusions and Relevance: The use of OT is associated with connectivity changes within the visual cortex. This case-control cohort study suggests that there is a visual connection to smell that has not been previously explored with OT and that further studies examining the efficacy of a bimodal visual and OT program are needed.

Randomized clinical trial to evaluate mometasone lavage vs spray for patients with chronic rhinosinusitis without nasal polyps who have not undergone sinus surgery.

BACKGROUND: There is no consensus regarding the best route of intranasal delivery of corticosteroids in the treatment of chronic rhinosinusitis (CRS). The study objective of this work was to compare the impact of mometasone furoate nasal spray (MFNS) vs mometasone nasal irrigation in the management of CRS patients who have not undergone sinus surgery. METHODS: A double-blind, placebo-controlled, randomized clinical trial was conducted in adults with CRS. Individuals with nasal polyps and/or history of sinus surgery were excluded. Patients were randomized to receive 8 weeks of either MFNS or mometasone nasal irrigation. The primary outcome measure was change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score between the 2 groups. Secondary outcome measures included patient global response to treatment and Lund-Kennedy endoscopy scores. RESULTS: A total of 43 participants completed the study (n = 22, MFNS; n = 21,mometasone nasal irrigation). Fourteen (64%) participants in the MFNS group and 17 (81%) in the mometasone lavage group had a clinically meaningful improvement in SNOT-22 scores with a proportion difference of 17% (95% confidence interval [CI], -9% to 44%). The least-squares (LS) mean difference between the 2 groups for SNOT-22 was -8.6 (95% CI, -17.7 to 0.58; p = 0.07), whereas the LS mean difference between the 2 groups for Lund-Kennedy endoscopy scores was 0.16 (95% CI, -0.84 to 1.15; p = 0.75). No adverse events were associated with the study. CONCLUSION: Both MFNS and mometasone nasal irrigations are beneficial in symptom management of CRS. Our study suggests that patients who perform mometasone lavage do better in a clinically meaningful way, but our results are not definitive and further studies are warranted.

Trend of surgery for orbital cellulitis: An analysis of state inpatient databases.

OBJECTIVES/HYPOTHESIS: To evaluate the trend and factors associated with surgical management of orbital cellulitis. STUDY DESIGN: Retrospective database study. METHODS: Study using the State Inpatient Databases (SIDs) from 2008 to 2015. Patients with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for orbital cellulitis were identified in the SIDs for the following states: Arkansas, Florida, Iowa, Maryland, Nebraska, New York, and Wisconsin. Surgery was defined as an ICD-9-CM procedure code for orbitotomy and/or functional endoscopic sinus surgery. The trend of surgery over time was evaluated using the Cochran-Armitage test. Multivariable logistic regression models were used to identify patient- and hospital-level factors associated with surgery. RESULTS: From 2008 to 2013, the number of hospitalizations for orbital cellulitis ranged from 1,349 to 1,574, but declined to 865 in 2014. From 2008 to 2015, the number of surgeries ranged from 103 to 154. For children (n = 3,041), age, ophthalmologic comorbidity, and conjunctival edema were significantly associated with surgery, whereas for adults (n = 7,961), male gender, private insurance, optic neuritis, and cranial nerves III/VI/VI palsy were associated with surgery. CONCLUSIONS: Although the number of inpatient hospitalizations for orbital cellulitis has markedly declined, the number of surgeries for orbital cellulitis has remained fairly stable, leading to an observed higher proportion of hospitalized patients undergoing surgery. Future directions include extending the time frame to the present day to assess current rates of hospitalization and surgery. Knowledge of surgical trends and patient- and hospital-level characteristics associated with surgery may help improve management guidelines for and understanding of this vision-threatening disease. LEVEL OF EVIDENCE: NA Laryngoscope, 130:567-574, 2020.

Morphologic, intraoperative, and histologic risk factors for sinonasal inverted papilloma recurrence.

OBJECTIVE: Sinonasal inverted papillomas (IP) are benign neoplasms with a propensity for local recurrence. Many risk factors are reported, with little consistency between studies. This study aimed to comprehensively assess for demographic, imaging, histopathologic, and intraoperative risk factors for recurrence. METHODS: We performed a single-center retrospective cohort study of patients with pathologically diagnosed IP without malignancy who underwent surgical resection between 1997 and 2018. Eligible patients were identified through a database maintained by the Department of Pathology. Logistic regression identified variables associated with recurrence, and conjunctive consolidation was performed to create a predictive model. RESULTS: Of 76 subjects, 37% (n = 28) had recurrence. Median follow-up and time to recurrence were 2.9 (range 0.5-21.1) and 1.7 (range 0.2-13.0) years, respectively. Confirmed negative margins on histology were protective (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.08-0.85). Frontal sinus involvement (adjusted odds ratio [aOR] 5.83, 95% CI 1.20-28.37), incomplete resection (aOR 9.67, 95% CI 2.24-41.72), and presence of dysplasia (aOR 4.38, 95% CI 1.01-19.10) were significantly associated with recurrence on multivariable analysis. A three-level composite recurrence risk staging system was created by consolidating the above three variables. The recurrence risks of composite stage I, II, and III disease were 20%, 38%, and 100%, respectively. No demographic, imaging, staging, or surgical approach variables were associated with recurrence. CONCLUSION: Frontal sinus involvement, incomplete resection, and dysplasia were significant risk factors for IP recurrence, whereas confirmed negative margins were protective. Creation of a composite staging system using the above variables may allow for risk stratification and a patient-specific approach to postoperative IP management. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:590-596, 2020.

Development of a Mixed Reality Platform for Lateral Skull Base Anatomy.

OBJECTIVES: A mixed reality (MR) headset that enables three-dimensional (3D) visualization of interactive holograms anchored to specific points in physical space was developed for use with lateral skull base anatomy. The objectives of this study are to: 1) develop an augmented reality platform using the headset for visualization of temporal bone structures, and 2) measure the accuracy of the platform as an image guidance system. METHODS: A combination of semiautomatic and manual segmentation was used to generate 3D reconstructions of soft tissue and bony anatomy of cadaver heads and temporal bones from 2D computed tomography images. A Mixed-Reality platform was developed using C# programming to generate interactive 3D holograms that could be displayed in the HoloLens headset. Accuracy of visual surface registration was determined by target registration error between seven predefined points on a 3D holographic skull and 3D printed model. RESULTS: Interactive 3D holograms of soft tissue, bony anatomy, and internal ear structures of cadaveric models were generated and visualized in the MR headset. Software user interface was developed to allow for user control of the virtual images through gaze, voice, and gesture commands. Visual surface point matching registration was used to align and anchor holograms to physical objects. The average target registration error of our system was 5.76 mm ±â€Š0.54. CONCLUSION: In this article, we demonstrate that an MR headset can be applied to display interactive 3D anatomic structures of the temporal bone that can be overlaid on physical models. This technology has the potential to be used as an image guidance tool during anatomic dissection and lateral skull base surgery.