Label-free histomorphometry of peripheral nerve by stimulated Raman spectroscopy.

BACKGROUND: Conventional processing of nerve for histomorphometry is resource-intensive, precluding use in intraoperative assessment of nerve quality during nerve transfer procedures. Stimulated Raman scattering (SRS) microscopy is a label-free technique that enables rapid and high-resolution histology. METHODS: Segments of healthy murine sciatic nerve, healthy human obturator nerve, and human cross-facial nerve autografts were imaged on a custom SRS microscope. Myelinated axon quantification was performed through segmentation using a random forest machine learning algorithm in commercial software. RESULTS: High contrast, high-resolution imaging of nerve morphology was obtained with SRS imaging. Automated myelinated axon quantification from cross-sections of healthy human nerve imaged using SRS was achieved. CONCLUSIONS: Herein, we demonstrate the use of a label-free technique for rapid imaging of murine and human peripheral nerve cryosections. We illustrate the potential of this technique to inform intraoperative decision-making through rapid automated quantification of myelinated axons using a machine learning algorithm.

Long-Term Outcomes of Free Gracilis Muscle Transfer for Smile Reanimation in Children.

OBJECTIVE: To evaluate long-term outcomes of free gracilis muscle transfer (FGMT) for smile reanimation on smile excursion, facial symmetry, and quality of life in a cohort of children with facial palsy. STUDY DESIGN: A retrospective analysis of 40 pediatric patients who underwent FGMT for facial palsy at the Massachusetts Eye and Ear Infirmary Facial Nerve Center was performed. Preoperative and postoperative photography and videography were used to quantify smile excursion and facial symmetry. Preoperative and postoperative quality of life was assessed with the Facial Clinimetric Evaluation (FaCE) survey, a validated, patient-based instrument for evaluating facial impairment and disability. RESULTS: Of the 40 patients who underwent FGMT for facial palsy, 38 patients had complete data including preoperative and postoperative photography and videography from 3 months to 10 years following surgery; 13 cases had >5 years of follow-up. FGMT resulted in significant improvements in smile excursion within several months, with continued improvements in smile excursion and symmetry demonstrated more than 5 years later. Fifteen patients completed preoperative and postoperative FaCE surveys, which demonstrated significant improvement in quality of life scores following FGMT. CONCLUSIONS: FGMT significantly improves smile, facial asymmetry, and quality of life for years after this surgery for facial palsy.

Functional and Cosmetic Considerations in Gender-Affirming Feminization Rhinoplasty.

Gender-affirming facial surgery is increasing in prevalence, and rhinoplasty plays an integral role in its success. The nose displays considerable gender dimorphism, and maneuvers performed during gender-affirming rhinoplasty may differ considerably from those performed during cis-gender surgery. During feminization rhinoplasty in particular, cosmetic goals often rely on reductive techniques such as osteotomies, dorsal reduction, sidewall narrowing, tip narrowing, and alar base narrowing. These maneuvers collectively have important ramifications when considering the functional aspects of the nose. Herein, we outline the status of feminization rhinoplasty, and the interplay of cosmetic and functional considerations of the field.

Applications of artificial intelligence in facial plastic and reconstructive surgery: a systematic review.

PURPOSE OF REVIEW: Arguably one of the most disruptive innovations in medicine of the past decade, artificial intelligence is dramatically changing how healthcare is practiced today. A systematic review of the most recent artificial intelligence advances in facial plastic surgery is presented for surgeons to stay abreast of the latest in our field. RECENT FINDINGS: Artificial intelligence applications developed for use in perioperative patient evaluation and management, education, and research in facial plastic surgery are highlighted. Selected themes include automated facial analysis with landmark detection, automated facial palsy grading and emotional assessment, generation of artificial facial profiles for testing and model training, automated postoperative patient communications, and improving ethnicity-sensitive facial morphometry norms. Inherent bias can exist in artificial intelligence models, and care must be taken to utilize algorithms trained with diverse datasets. SUMMARY: Artificial intelligence tools are helping clinicians provide more standardized, objective, and efficient care to their patients. Increasing surgeon awareness of available tools, and their widespread implementation into clinical workflows are the next frontier. Ethical considerations must also shape the adoption of any artificial intelligence functionality. As artificial intelligence applications become a fixture in medicine, surgeons must employ them effectively to stay at the vanguard of modern medicine.

Sacral metastases in a patient with BRAF V600E+ papillary thyroid carcinoma.

Lack of consensus exists on an algorithm to screen for synchronous distant metastases in patients presenting with papillary thyroid carcinoma (PTC). A 68-year-old male presented with a 3 cm supraclavicular neck mass. Computed tomography (CT) scan revealed a 1.3 cm left thyroid lobe nodule and 3 cm left level 3 and 4 lymphadenopathy. Ultrasound-guided fine needle aspiration was positive for PTC. Patient underwent total thyroidectomy and lymph node dissection with molecular testing confirming BRAF V600E+ PTC. Six weeks post-operatively, he developed left hip pain and numbness. Magnetic resonance imaging (MRI) revealed a large sacral mass and multiple bony lesions confirmed to be osseous metastases. Given the relatively rapid report of hip pain after surgery, metastases were likely synchronous at presentation and may have been detected with earlier suspicion. Further investigation is necessary to systematically stratify risk of synchronous distant metastases in patients with metastatic PTC.

Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis.

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.

Super-resolved fluorescence imaging of peripheral nerve.

Traditional histopathologic evaluation of peripheral nerve employs brightfield microscopy with diffraction limited resolution of ~ 250 nm. Though electron microscopy yields nanoscale resolution of the nervous system, sample preparation is costly and the technique is incompatible with living samples. Super-resolution microscopy (SRM) comprises a set of imaging techniques that permit nanoscale resolution of fluorescent objects using visible light. The advent of SRM has transformed biomedical science in establishing non-toxic means for investigation of nanoscale cellular structures. Herein, sciatic nerve sections from GFP-variant expressing mice, and regenerating human nerve from cross-facial autografts labelled with a myelin-specific fluorescent dye were imaged by super-resolution radial fluctuation microscopy, stimulated emission depletion microscopy, and structured illumination microscopy. Super-resolution imaging of axial cryosections of murine sciatic nerves yielded robust visualization myelinated and unmyelinated axons. Super-resolution imaging of axial cryosections of human cross-facial nerve grafts demonstrated enhanced resolution of small-caliber thinly-myelinated regenerating motor axons. Resolution and contrast enhancement afforded by super-resolution imaging techniques enables visualization of unmyelinated axons, regenerating axons, cytoskeleton ultrastructure, and neuronal appendages of mammalian peripheral nerves using light microscopes.

Automated stain-free histomorphometry of peripheral nerve by contrast-enhancing techniques and artificial intelligence.

BACKGROUND: Traditional histopathologic evaluation of peripheral nerve using brightfield microscopy is resource-intensive, necessitating complex sample preparation. Label-free imaging techniques paired with artificial intelligence-based image reconstruction and segmentation may facilitate peripheral nerve histomorphometry. NEW METHOD: Herein, the utility of label-free phase contrast techniques paired with artificial intelligence-based image processing for imaging of mammalian peripheral nerve is demonstrated. RESULTS: Fresh frozen murine sciatic nerve sections were imaged in transmission modalities using differential interference and phase contrast microscopy and in epifluorescent modality following staining with myelin-specific dye. Deep learning was employed to predict epifluorescent images from transmitted phase contrast images, and machine learning employed for automated segmentation of myelinated axons for reporting of axons counts and g-ratios. COMPARISON WITH EXISTING METHODS: Conventional peripheral nerve histomorphometry employs resource intensive resin embedding, ultra-microtome sectioning, and staining steps. Herein we demonstrate feasibility of high-throughput nerve histomorphometry via label-free phase contrast imaging of frozen sections. CONCLUSIONS: Clinical applications of label-free phase contrast microscopy paired with deep learning algorithms are discussed.

Considerations in Management of Acute Otitis Media in the COVID-19 Era.

OBJECTIVES: To present the otologic findings of a patient with COVID-19 and complicated acute otitis media, evaluate for the presence of SARS-CoV-2 in middle ear fluid, and assess whether suctioning of middle ear fluid may be aerosol- generating. METHODS: The case of a man with SARS-CoV-2 infection and complicated acute otitis media with facial paralysis is presented to illustrate unique clinical decisions made in context of the COVID-19 pandemic. A cadaveric temporal bone was used to simulate droplet spread during suctioning of fluorescein-labelled middle ear fluid and visualized with a blue-light filter. RESULTS: A 23-year-old male who presented with complicated acute otitis media with facial paralysis was found to have an acute infection with SARS-CoV-2, with positive viral PCR of nasopharyngeal swab, and a negative PCR of the middle ear fluid. He was placed on isolation precautions and treated with myringotomy, topical and systemic antibiotics, and antivirals. Consistent with observations during endonasal suctioning, suctioning of middle ear fluid was not found to be aerosol or droplet generating. CONCLUSION: The case of a patient with active COVID-19 presenting with complicated acute otitis media in whom middle ear fluid was sampled to evaluate the etiology of the infection and the potential middle ear predilection of SARS-CoV-2 is described. This study has implications for the clinical management of patients with both known and unknown SARS-CoV-2 infection who present with ear disease. While middle ear suctioning may not be aerosol-generating, the risk of coughing or prolonged close contact requires heightened precautions during otologic procedures in patients with suspected or confirmed COVID-19.

Embolization of the internal maxillary artery via open retrograde superficial temporal artery approach.

Sentinel bleeds in head and neck cancer patients present as an ominous symptom often necessitating urgent endovascular embolization. However, this approach can be complicated in patients who have previously undergone head and neck cancer ablation and reconstruction, thus altering the standard arterial vascular supply. Herein we describe an innovative method of internal maxillary artery (IMA) access in a patient with a sentinel bleed who previously underwent proximal external carotid artery (ECA) rerouting for free flap reconstruction. The open retrograde superficial temporal artery approach for IMA embolization is minimally invasive and effective and should be considered for head and neck cancer patients at risk of hemorrhage from distal ECA branches without a proximal ECA embolization option.

An Anatomic Variant of the Ansa Cervicalis Precluding Its Use as a Donor Nerve.

BACKGROUND: The ansa cervicalis is useful for cranial nerve repair, and may be harvested without apparent morbidity. Herein we report an unusual and surgically relevant anatomic variant of the ansa cervicalis. METHODS: An adult male with left parotid adenoid cystic carcinoma underwent parotidectomy with upper-division facial nerve resection and planned interposition repair using the ansa cervicalis. The ipsilateral hypoglossal nerve was identified, together with a descending branch producing strap muscle contraction when stimulated. This presumed descendens hypoglossi was unusually large in caliber; further dissection revealed continuity with the vagus nerve. RESULTS: Ansa cervicalis harvest was aborted when its separation from vagus nerve epineurium was not possible. The sural nerve was alternatively harvested. The patient awoke with left vocal fold palsy, which completely resolved within 3 months. CONCLUSION: Anatomic variants of the ansa cervicalis exist that may preclude graft harvest and place the vagus nerve at risk of inadvertent injury.

Implantable wireless device for study of entrapment neuropathy.

BACKGROUND: Disease processes causing increased neural compartment pressure may induce transient or permanent neural dysfunction. Surgical decompression can prevent and reverse such nerve damage. Owing to insufficient evidence from controlled studies, the efficacy and optimal timing of decompression surgery remains poorly characterized for several entrapment syndromes. NEW METHOD: We describe the design, manufacture, and validation of a device for study of entrapment neuropathy in a small animal model. This device applies graded extrinsic pressure to a peripheral nerve and wirelessly transmits applied pressure levels in real-time. We implanted the device in rats applying low (under 100 mmHg), intermediate (200-300 mmHg) and high (above 300 mmHg) pressures to induce entrapment neuropathy of the facial nerve to mimic Bell's palsy. Facial nerve function was quantitatively assessed by tracking whisker displacements before, during, and after compression. RESULTS: At low pressure, no functional loss was observed. At intermediate pressure, partial functional loss developed with return of normal function several days after decompression. High pressure demonstrated complete functional loss with incomplete recovery following decompression. Histology demonstrated uninjured, Sunderland grade III, and Sunderland grade V injury in nerves exposed to low, medium, and high pressure, respectively. COMPARISON WITH EXISTING METHODS: Existing animal models of entrapment neuropathy are limited by inability to measure and titrate applied pressure over time. CONCLUSIONS: Described is a miniaturized, wireless, fully implantable device for study of entrapment neuropathy in a murine model, which may be broadly employed to induce various degrees of neural dysfunction and functional recovery in live animal models.

Associations between national financial trends and facial plastic surgery procedural volume.

OBJECTIVE(S): To characterize procedural trends in facial plastic and reconstructive surgery procedures in relation to the United States economy. METHODS: Retrospective cohort study examining annual procedure rates were determined from the American Society of Plastic Surgeons (ASPS) National Clearinghouse of Plastic Surgery Procedural Statistics from January 1 2007 to December 30, 2017. Procedures were compared to economic activity of the United States as measured by gross domestic product (GDP) were compared using Kolmogorov-Smirnov goodness of fit testing and piecewise multivariate regression modeling. RESULTS: Annual trends in procedural rates showed an overall decrease in the rates of rhinoplasty (284,960 to 218,924), blepharoplasty (240,660 to 209,571), and otoplasty (28,571 to 23,433) from 2007 to 2017. Total cosmetic surgery remained fairly stable, while minimally invasive cosmetic surgery increased in frequency over the study period. On piecewise regression analysis, rhinoplasty (P = .02), rhytidectomy (P = .007), invasive cosmetic surgery (P < .001) were significantly associated with GDP, whereas otoplasty (P = .98) and reconstructive surgery (P = .11) were not associated with GDP. CONCLUSION: Cosmetic plastic surgery procedures show a greater correlation to GDP than reconstructive procedures. Trends in plastic surgery cases over the last decade show a decreasing number of rhinoplasty, otoplasty, and blepharoplasty, with stabilization in the last few years. An increasing number of reconstructive cases are found. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:632-636, 2020.

Toward an Automatic System for Computer-Aided Assessment in Facial Palsy.

Importance: Quantitative assessment of facial function is challenging, and subjective grading scales such as House-Brackmann, Sunnybrook, and eFACE have well-recognized limitations. Machine learning (ML) approaches to facial landmark localization carry great clinical potential as they enable high-throughput automated quantification of relevant facial metrics from photographs and videos. However, the translation from research settings to clinical application still requires important improvements. Objective: To develop a novel ML algorithm for fast and accurate localization of facial landmarks in photographs of facial palsy patients and utilize this technology as part of an automated computer-aided diagnosis system. Design, Setting, and Participants: Portrait photographs of 8 expressions obtained from 200 facial palsy patients and 10 healthy participants were manually annotated by localizing 68 facial landmarks in each photograph and by 3 trained clinicians using a custom graphical user interface. A novel ML model for automated facial landmark localization was trained using this disease-specific database. Algorithm accuracy was compared with manual markings and the output of a model trained using a larger database consisting only of healthy subjects. Main Outcomes and Measurements: Root mean square error normalized by the interocular distance (NRMSE) of facial landmark localization between prediction of ML algorithm and manually localized landmarks. Results: Publicly available algorithms for facial landmark localization provide poor localization accuracy when applied to photographs of patients compared with photographs of healthy controls (NRMSE, 8.56 ± 2.16 vs. 7.09 ± 2.34, p ≪ 0.01). We found significant improvement in facial landmark localization accuracy for the facial palsy patient population when using a model trained with a relatively small number photographs (1440) of patients compared with a model trained using several thousand more images of healthy faces (NRMSE, 6.03 ± 2.43 vs. 8.56 ± 2.16, p ≪ 0.01). Conclusions and Relevance: Retraining a computer vision facial landmark detection model with fewer than 1600 annotated images of patients significantly improved landmark detection performance in frontal view photographs of this population. The new annotated database and facial landmark localization model represent the first steps toward an automatic system for computer-aided assessment in facial palsy. Level of Evidence: 4.

Stain-Free Resolution of Unmyelinated Axons in Transgenic Mice Using Fluorescence Microscopy.

Though unmyelinated fibers predominate axon counts within peripheral nerves, they are frequently excluded in histomorphometric assessment as they cannot be readily resolved by light microscopy. Herein, we demonstrate stain-free resolution of unmyelinated axons in Sox10-Venus mice by widefield fluorescence imaging of sciatic nerve cryosections. Optional staining of cryosections using a rapid and nontoxic myelin-specific dye (FluoroMyelin Red) enables robust synchronous resolution of myelinated and unmyelinated fibers, comprising a high-throughput platform for neural histomorphometry.

A Comparative Health Utility Value Analysis of Outcomes for Patients Following Septorhinoplasty With Previous Nasal Surgery.

IMPORTANCE: Using health utility values (HUVs) as an outcome measure for surgical procedures, including rhinoplasty, allows for a standardized measurement of the qualitative and financial benefit of that procedure on overall health. OBJECTIVE: To use Euroqol 5-Dimension (EQ-5D)-derived HUVs to evaluate nasal obstruction outcomes following surgery between primary rhinoplasty (PSRP) and rhinoplasty with previous nasal surgery (RNS) in a prospective cohort study. DESIGN, SETTING, AND PARTICIPANTS: A single-institution prospective cohort study between 2013 and 2017 was carried out including 185 patients who underwent RNS before functional rhinoplasty and 278 patients who underwent PSRP for nasal obstruction. The analysis was carried out between December 2018 and February 2019. MAIN OUTCOMES AND MEASURES: Patients in the RNS cohort and PSRP cohort who completed the EQ-5D questionnaire immediately prior to surgery and postoperatively at 2, 4, 6, and 12 months were included in the study. The EQ-5D scores were converted to HUV scores and compared to evaluate for improvement in health status following surgery. RESULTS: Of the 185 patients in the RNS cohort, 97 (52%) were women and the mean (SD) age was 42.6 (13.4) years. Of the 278 in the PSRP cohort, 156 (55%) were women and the mean (SD) age was 36.0 (15.8) years. Both cohorts experienced significant improvement in HUV postoperatively. The mean (SD) HUV values were decreased in the RNS cohort versus the PSRP cohort both preoperatively (0.85 [0.16] versus 0.89 [0.14]) and postoperatively at 1 year (0.92 [0.14] versus 0.94 [0.11]); however, the difference in HUV was not statistically significant after 6 months postoperatively. Patients in the RNS cohort were typically older (76 [41%] older than 40 years vs 84 [31%], P = .02) and more likely to have sleep apnea (31 [19%] vs 24 [10%], P = .01) than in the PSRP cohort. On multivariable analysis, the use of spreader grafts and alar rim grafts in the PSRP cohort was significantly associated with improved HUV at 12 months. (r = -0.06; 95% CI, -0.11 to -0.01, P = .03). CONCLUSIONS AND RELEVANCE: Patients with a history of prior nasal surgery may represent a unique cohort when assessing health utility outcomes. Euroqol 5-dimension questionnaire-derived HUVs are a valid predictor of outcomes in all patients who undergo septorhinoplasty. Although outcomes were significantly improved for both cohorts, previous surgical history should be considered when performing cost utility analysis on the benefits of functional rhinoplasty. LEVEL OF EVIDENCE: 3.

Health Utility Values as an Outcome Measure in Patients Undergoing Functional Septorhinoplasty.

IMPORTANCE: By measuring health utility values (HUVs) for patients with nasal obstruction after septorhinoplasty, the association of nasal congestion with overall health can be measured and the functional outcomes of septorhinoplasty can be determined. OBJECTIVE: To use the EuroQol 5-Dimension (EQ-5D) questionnaire to evaluate nasal obstruction outcomes after septorhinoplasty and to determine HUVs. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included patients who underwent septorhinoplasty for nasal obstruction at a single institution by a single surgeon from January 1, 2013, through December 31, 2017. Participants completed the EQ-5D questionnaire immediately before surgery and postoperatively at 2, 4, 6, and 12 months. The EQ-5D scores were converted to HUVs using population-based data for individuals with chronic diseases. Data were analyzed from May 1 through December 31, 2018. EXPOSURE: Functional septorhinoplasty. MAIN OUTCOMES AND MEASURES: Preoperative and postoperative EQ-5D scores were compared to evaluate improvement in overall health after septorhinoplasty. RESULTS: A total of 463 patients (53.8% women; mean [SD] age, 36.8 [15.7] years) who underwent septorhinoplasty and completed EQ-5D surveys at baseline and postoperatively were included in the study population. Overall mean (SD) preoperative HUV was 0.872 (0.01), compared with 1.00 for those with a perfect state of health. On univariate analysis, female sex (mean [SD] HUV, 0.853 [0.01]; P = .004), previous nasal surgery (mean [SD] HUV, 0.85 [0.16]; P = .02), previous septoplasty (mean [SD] HUV, 0.88 [0.15]; P = .02), and previous sinus surgery (mean [SD] HUV, 0.79 [0.20]; P = .009) were associated with significantly lower baseline HUVs. On multivariate regression including these variables, only previous septoplasty was significantly associated with a positive change in mean (SD) HUV (0.88 [0.15] vs 0.85 [0.16]; P = .02). Mean (SD) HUV was significantly improved at 2 months postoperatively to 0.91 (0.14; P = .001) and remained significantly improved from baseline at 12 months, at 0.93 (0.13; P < .001). CONCLUSIONS AND RELEVANCE: Nasal obstruction is associated with significant detriment to overall health, in line with other chronic conditions affecting the US population. Functional septorhinoplasty appears to substantially improve overall health, as measured by HUV, in an immediate and sustained fashion. LEVEL OF EVIDENCE: 3.

Opioids and the Otolaryngologist: An Ambulatory Assessment.

Objectives To recognize current opioid prescription patterns in otolaryngology and determine changes in rates of outpatient opioid prescribing over time. Study Design Cross-sectional analysis of national survey database. Setting Ambulatory care settings in the United States. Subjects and Methods The National Ambulatory Medical Care Survey from 2006 to 2013 was analyzed for outpatient otolaryngology visits. The rate of opioid medication prescribing was determined with patient and visit characteristics associated with an opioid prescription, including corresponding diagnoses. Calendar trends for the rate of opioid prescribing were determined and compared biennially. Results Among 19.2 ± 1.7 million otolaryngology visits annually (raw N = 11,905), there were 728,000 ± 96,000 visits with an opioid prescription (3.8% ± 0.4%). Adults were more likely than children to receive a narcotic (4.3% vs 1.9%, P < .001); there was no significant difference according to sex (3.9% female vs 3.7% male, P = .567). With respect to calendar trend, the opioid prescription rate increased significantly from 2.3% in 2006-2007 to 4.6% in 2008-2011 and then decreased to 3.5% in 2012-2013 ( P < .031). The most common visit diagnosis categories associated with opioid prescribing were as follows: postoperative care (19.7% of prescriptions), adenotonsillitis (13.9%), chronic otitis media (8.7%), otitis externa (6.2%), and nasal obstruction (5.6%). Conclusion Despite the opioid epidemic in the United States, only a small portion of otolaryngology visits were associated with opioid prescription. However, given the significant increase in prescribing from 2008 to 2011, continued surveillance of prescribing patterns is warranted.

Outcome Tracking in Facial Palsy.

Outcome tracking in facial palsy is multimodal, consisting of patient-reported outcome measures, clinician-graded scoring systems, objective assessment tools, and novel tools for layperson and spontaneity assessment. Patient-reported outcome measures are critical to understanding burden of disease in facial palsy and effects of interventions from the patient perspective. Clinician-graded scoring systems are inherently subjective and no 1 single system satisfies all needs. Objective assessment tools quantify facial movements but can be laborious. Recent advances in facial recognition technology have enabled automated facial measurements. Novel assessment tools analyze attributes such as spontaneous smile, emotional expressivity, disfigurement, and attractiveness as determined by laypersons.