Augmented Virtual Examination for Cosmetic and Functional Rhinoplasty.

Background: Few studies have critically evaluated the quality of data obtained during telemedical evaluations of patients with nasal complaints. Objective: To compare the quality of data provided by remote endoscopic and external nasal examination with those by in-person evaluations for rhinoplasty and functional nasal surgery, measured by detectability of anatomic features, and to assess associated patient experience measured by reported ease, discomfort, and likelihood of peer recommendation. Materials and Methods: Twenty healthy subjects performed a nasal self-examination using an endoscope and webcam under remote videoconferencing service (VCS) guidance. They subsequently underwent in-person examination and were surveyed about their experience. Inter-rater reliability was calculated using kappa coefficients. Detectability of anatomic features by in-person versus virtual examination was compared using Wilcoxon and chi-square tests. Results: Median subject age was 27.5 years (range 23-77). Kappa coefficients were 0.78 for in-person and 0.66 for virtual evaluations. Only the internal nasal valve and inferior turbinate were better visualized in person. There were no differences between detectability of external features on in-person versus virtual examinations. Subjects' average likelihood of recommending this technology (1-10) was 8.65 (SD 1.4). Conclusions: Intranasal examination by physician-guided remote endoscopy and webcam-based facial analysis demonstrate nasal anatomy comparable with in-person evaluation and anterior rhinoscopy.

GMP-grade human neural progenitors delivered subretinally protect vision in rat model of retinal degeneration and survive in minipigs.

BACKGROUND: Stem cell products are increasingly entering early stage clinical trials for treating retinal degeneration. The field is learning from experience about comparability of cells proposed for preclinical and clinical use. Without this, preclinical data supporting translation to a clinical study might not adequately reflect the performance of subsequent clinical-grade cells in patients. METHODS: Research-grade human neural progenitor cells (hNPC) and clinical-grade hNPC (termed CNS10-NPC) were injected into the subretinal space of the Royal College of Surgeons (RCS) rat, a rodent model of retinal degeneration such as retinitis pigmentosa. An investigational new drug (IND)-enabling study with CNS10-NPC was performed in the same rodent model. Finally, surgical methodology for subretinal cell delivery in the clinic was optimized in a large animal model with Yucatan minipigs. RESULTS: Both research-grade hNPC and clinical-grade hNPC can survive and provide functional and morphological protection in a dose-dependent fashion in RCS rats and the optimal cell dose was defined and used in IND-enabling studies. Grafted CNS10-NPC migrated from the injection site without differentiation into retinal cell phenotypes. Additionally, CNS10-NPC showed long-term survival, safety and efficacy in a good laboratory practice (GLP) toxicity and tumorigenicity study, with no observed cell overgrowth even at the maximum deliverable dose. Finally, using a large animal model with the Yucatan minipig, which has an eye size comparable to the human, we optimized the surgical methodology for subretinal cell delivery in the clinic. CONCLUSIONS: These extensive studies supported an approved IND and the translation of CNS10-NPC to an ongoing Phase 1/2a clinical trial (NCT04284293) for the treatment of retinitis pigmentosa.

Outcomes of Gender-Affirming Voice and Communication Modification Training for Non-binary Individuals: A Case Series.

OBJECTIVES: There is currently no research reporting solely on outcomes of voice and communication modification training (VCMT) in individuals who identify as non-binary and genderqueer (NBGQ) in the English literature. This study aimed to describe the objective and subjective impact of VCMT on the voice of NBGQ individuals undergoing a 12-week gender-affirming VCMT program. METHODS: A retrospective consecutive case series of NBGQ individuals enrolled in a VCMT program was performed. Demographics, Transgender Self-Evaluation Questionnaire (TSEQ), fundamental frequency (F0), and frequency range were collected before and after the program. RESULTS: Four NBGQ individuals enrolled between January 2019 and June 2021; the mean age was 27.0 years. While all four participants represented in this case series showed improvement in at least one of their initial goals, only one improved both their F0 and TSEQ scores; the other three participants had mixed results. CONCLUSION: NBGQ individuals experienced improvements in self-reported outcomes and changes in acoustic measures after completing VCMT in our case series. Individuals experienced significant improvement in subjective outcomes despite small changes in acoustic measures, and vice versa. More research is needed to better understand the voice and communication needs of NBGQ individuals, along with their outcomes with VCMT. LEVEL OF EVIDENCE: Level 4.

Differential effects of exposure to toxic or nontoxic mold spores on brain inflammation and Morris water maze performance.

People who live or work in moldy buildings often complain of "brain fog" that interferes with cognitive performance. Until recently, there was no published research on the effects of controlled exposure to mold stimuli on cognitive function or an obvious mechanism of action, fueling controversy over these claims. The constellation of health problems reported by mold-exposed individuals (respiratory issues, fatigue, pain, anxiety, depression, and cognitive deficits) correspond to those caused by innate immune activation following exposure to bacterial or viral stimuli. To determine if mold-induced innate immune activation might cause cognitive issues, we quantified the effects of both toxic and nontoxic mold on brain immune activation and spatial memory in the Morris water maze. We intranasally administered either 1) intact, toxic Stachybotrys chartarum spores; 2) ethanol-extracted, nontoxic Stachybotrys chartarum spores; or 3) control saline vehicle to mice. Inhalation of nontoxic spores caused significant deficits in the test of long-term memory of platform location, while not affecting short-term memory. Inhalation of toxic spores increased motivation to reach the platform. Interestingly, in both groups of mold-exposed males, numbers of interleukin-1ß-immunoreactive cells in many areas of the hippocampus significantly correlated with latency to find the platform, path length, and swimming speed during training, but not during testing for long-term memory. These data add to our prior evidence that mold inhalation can interfere with cognitive processing in different ways depending on the task, and that brain inflammation is significantly correlated with changes in behavior.

Pegcetacoplan treatment for geographic atrophy due to age-related macular degeneration: a plain language summary of the FILLY study.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a publication about the FILLY study, which was published in Ophthalmology in 2020. The FILLY study looked at an investigational medicine called pegcetacoplan as a possible treatment for geographic atrophy. Geographic atrophy, also known as GA, is the late stage of an eye disease called dry age-related macular degeneration, also known as dry AMD. In people with GA, lesions form on a part of the back of the eye called the retina. GA lesions are patches of thin retina. Growth of GA lesions ultimately causes blindness, which cannot be reversed. There is currently no approved treatment for GA. Pegcetacoplan, also called APL-2, could be a possible treatment for GA. Pegcetacoplan is an investigational medicine, which means it has not yet been approved. It is currently being studied in clinical studies to see how well it works. WHAT HAPPENED IN THE FILLY STUDY?: The FILLY study included participants with GA and tested how well pegcetacoplan worked compared to a sham injection (an injection that looks like the study treatment but does not have any medicine in it). The study also looked at how safe it was in adults with GA. WHAT WERE THE RESULTS?: The main questions the researchers wanted to answer were: Did pegcetacoplan slow the growth of the study participants' GA lesions? ○Yes. Overall, the researchers found that pegcetacoplan did slow the growth of the study participants' GA lesions. Did pegcetacoplan change the participants' vision? ○No. Overall, the researchers found that pegcetacoplan did not change the participants' vision. What medical problems happened after the participants received pegcetacoplan? ○The researchers kept track of any serious medical problems that happened during the study, also called serious adverse events. They also kept track of other medical problems that happened, or got worse, only at some point after the participants received the study treatment. These are called treatment emergent adverse events, also known as TEAEs. The serious adverse events and TEAEs that the participants had are described later in this summary. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, results from this study showed that participants who received pegcetacoplan had slower growth of GA lesions than participants who received the sham injection. After the participants had stopped receiving pegcetacaoplan, the effect of the treatment seemed to be reduced. Pegcetacoplan did not change how well the participants could see during their vision tests in this trial. ClinicalTrials.gov NCT number: NCT02503332.

What's in a Name? A Cost-Effectiveness Analysis of the Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features' Nomenclature Revision.

Background: The noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (eFVPTC) has been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reflect the indolent behavior and favorable prognosis of this type of tumor. This terminology change has also de-escalated its management approach from cancer treatment to a more conservative treatment strategy befitting a benign thyroid neoplasm. Objective: To characterize the reduced health care costs and improved quality of life (QOL) from management of NIFTP as a nonmalignant tumor compared with the previous management as eFVPTC. Methods: A cost-effectiveness analysis was performed by creating Markov models to simulate two management strategies for NIFTP: (i) de-escalated management of the tumor as NIFTP involving lobectomy with reduced follow-up, (ii) management of the tumor as eFVPTC involving completion thyroidectomy/radioactive iodine ablation for some patients, and follow-up recommended for carcinoma. The model was simulated for 5 and 20 years following diagnosis of NIFTP. Aggregate costs and quality-life years were measured. One-way sensitivity analysis was performed for all variables. Results: Over a five-year simulation period, de-escalated management of NIFTP had a total cost of $12,380.99 per patient while the more aggressive management of the tumor as eFVPTC had a total cost of $16,264.03 per patient (saving $3883.05 over five years). Management of NIFTP provided 5.00 quality-adjusted life years, whereas management as eFVPTC provided 4.97 quality-adjusted life years. Sensitivity analyses showed that management of NIFTP always resulted in lower costs and greater quality-adjusted life years (QALYs) over the sensitivity ranges for individual variables. De-escalated management for NIFTP is expected to produce ∼$6-42 million in cost savings over a five-year period for these patients, and incremental 54-370 QALYs of increased utility in the United States. Conclusion: The degree of cost savings and improved patient utility of de-escalated NIFTP management compared with traditional management was estimated to be $3883.05 and 0.03 QALYs per patient. We demonstrate that these findings persisted in sensitivity analysis to account for variability in recurrence rate, surveillance approaches, and other model inputs. These findings allow for greater understanding of the economic and QOL impact of the NIFTP reclassification.

Impact of COVID-19 on Endoscopy Training: Perspectives from a Global Survey of Program Directors and Endoscopy Trainers.

BACKGROUND/AIMS: The coronavirus disease of 2019 (COVID-19) pandemic has impacted the training of medical trainees internationally. The aim of this study was to assess the global impact of COVID-19 on endoscopy training from the perspective of endoscopy trainers and to identify strategies implemented to mitigate the impact on trainee education. METHODS: Teaching faculty of gastroenterology (GI) training programs globally were invited to complete a 36-question web-based survey to report the characteristics of their training programs and the impact of COVID-19 on various aspects of endoscopy training, including what factors decisions were based on. RESULTS: The survey response rate was 52.6% (305 out of 580 individuals); 92.8% reported a negative impact on endoscopy training, with suspension of elective procedures (77.1%) being the most detrimental factor. Geographic variations were noted, with European programs reporting the lowest percentage of trainee participation in procedures. A higher proportion of trainees in the Americas were allowed to continue performing procedures, and trainers from the Americas reported receiving the greatest support for endoscopy teaching. CONCLUSION: This study demonstrated that the COVID-19 pandemic has had a significant negative impact on GI endoscopy training internationally, as reported by endoscopy trainers. Focus-optimizing endoscopy training and assessment of competencies are necessary to ensure adequate endoscopy training.

Impact of Nonadherence to NCCN Adjuvant Radiotherapy Initiation Guidelines in Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

BACKGROUND: Nonadherence to NCCN Guidelines during time from surgery to postoperative radiotherapy (S-PORT) can alter survival outcomes in head and neck squamous cell carcinomna (HNSCC). There is a need to validate this impact in an underserved urban population and to understand risk factors and reasons for delay. We sought to investigate the impact of delayed PORT with outcomes of overall survival (OS) in HNSCC, to analyze predictive factors of delayed PORT, and to identify reasons for delay. METHODS: We conducted a retrospective cohort study in an urban, community-based academic center. A total of 184 patients with primary HNSCC were identified through the Montefiore Medical Center cancer registry who had been treated between March 1, 2005, and March 8, 2017, and met the inclusion and exclusion criteria. The primary exposure was S-PORT. OS, recurrence, and risk factors and reasons for treatment delay were the main outcomes and measures. RESULTS: Among 184 patients with HNSCC treated with PORT, the median S-PORT was 48.5 days (interquartile range, 41-67 days). The S-PORT threshold that optimally differentiated worse OS outcomes was >50 days (46.7% of our cohort; n=86). Independent of other relevant factors, patients with HNSCC and S-PORT >50 days had worse OS (hazard ratio, 2.30; 95% CI, 1.34-3.95) and greater recurrence (odds ratio, 3.51; 95% CI, 1.31-9.39). Predictors of delayed S-PORT included being underweight or obese, prolonged postoperative length of stay, and age >70 years. The most frequent reasons for PORT delay were complications related to surgery (22.09%), unrelated medical comorbidities (18.60%), and nonadherence/missed appointments (6.98%). CONCLUSIONS: Delayed PORT beyond 50 days after surgery was associated with decreased OS and greater recurrence. Identification of predictive factors and reasons for treatment delay helps to target at-risk patients and facilitates interventions in underserved populations.

Tracheotomy Outcomes in 64 Ventilated COVID-19 Patients at a High-Volume Center in Bronx, NY.

OBJECTIVES/HYPOTHESIS: The COVID-19 pandemic has resulted in a dramatic increase in the number of patients requiring prolonged mechanical ventilation. Few studies have reported COVID-19 specific tracheotomy outcomes, and the optimal timing and patient selection criteria for tracheotomy remains undetermined. We delineate our outcomes for tracheotomies performed on COVID-19 patients during the peak of the pandemic at a major epicenter in the United States. METHODS: This is a retrospective observational cohort study. Mortality, ventilation liberation rate, complication rate, and decannulation rate were analyzed. RESULTS: Sixty-four patients with COVID-19 underwent tracheotomy between April 1, 2020 and May 19, 2020 at two tertiary care hospitals in Bronx, New York. The average duration of intubation prior to tracheotomy was 20 days ((interquartile range [IQR] 16.5-26.0). The mortality rate was 33% (n = 21), the ventilation liberation rate was 47% (n = 30), the decannulation rate was 28% (n = 18), and the complication rate was 19% (n = 12). Tracheotomies performed by Otolaryngology were associated with significantly improved survival (P < .05) with 60% of patients alive at the conclusion of the study compared to 9%, 12%, and 19% of patients undergoing tracheotomy performed by Critical Care, General Surgery, and Pulmonology, respectively. CONCLUSIONS: So far, this is the second largest study describing tracheotomy outcomes in COVID-19 patients in the United States. Our early outcomes demonstrate successful ventilation liberation and decannulation in COVID-19 patients. Further inquiry is necessary to determine the optimal timing and identification of patient risk factors predictive of improved survival in COVID-19 patients undergoing tracheotomy. LEVEL OF EVIDENCE: 4-retrospective cohort study Laryngoscope, 131:E1797-E1804, 2021.

The Valuation of Rhytidectomy in Different Economic Markets.

This study demonstrates that the trend of how rhytidectomy is valued can be used to determine not only the pricing of this good but also how receptive developing economic markets are to the export of cosmetic facial plastic surgery. This study seeks to analyze and compare the value of rhytidectomy in an established market and an emerging market. A cross-sectional survey was administered through public online forums to 162 casual observers in the United States and 74 casual observers in India. Participants were shown pre- and postoperative photos of 10 patients who underwent cosmetic rhinoplasty and 2 patients who did not undergo surgery. Observers were asked to quantify the perceived change in attractiveness, change in age, and willingness to pay (WTP). There is a similar nonlinear trend between WTP and change in attractiveness in both the United States and India. Baseline values of rhytidectomy in the United States and India have a similar ratio of 2.122 compared with the ratio between both countries in the 2018 Big Mac index. The comparison of the trend in WTP in the United States and India shows that facial cosmetic surgery functions as a luxury good in both an established market and an emerging market. Our model successfully approximates the relationship between each country's purchasing power parity. Since the market behavior of rhytidectomy can be predicted based on purchasing power parity, there may be an untapped market for facial cosmetic surgery among populations with growing economies.

Impact of Smoking on Survival Outcomes in HPV-Related Oropharyngeal Carcinoma: A Meta-analysis.

OBJECTIVE: Characterize the survival impact of smoking on HPV-related (human papillomavirus) oropharyngeal squamous cell carcinoma. DATA SOURCES: Articles from 2000 to 2019 in the PubMed, Embase, and Cochrane Library databases were systematically reviewed for content and inclusion/exclusion criteria. REVIEW METHODS: Two reviewers independently analyzed the databases for eligibility and quality of the articles. Demographic data, smoking history, and survival outcomes were recorded. Hazard ratios and 95% CIs were collectively analyzed through a random effects meta-analysis model. RESULTS: Fifteen articles were included in the meta-analysis for overall survival, disease-specific survival, disease-free survival, progression-free survival, and locoregional recurrence outcomes. The overall survival hazard ratio was 2.4 for ever having smoked (95% CI, 1.4-4.0; P = .0006, I2 = .384) and 3.2 for current smoking (95% CI, 2.2-4.6; P < .0001, I2 = 0). The hazard ratio for disease-specific survival in current smokers was 6.3 (95% CI, 1.3-29.3; P = .0194, I2 = 0). Ever smoking had a larger impact on overall survival and disease-specific survival than the 10-pack year smoking threshold. CONCLUSION: Smoking negatively affects survival in patients with HPV-related oropharyngeal carcinoma across all outcomes. Current smoking during treatment is associated with the greatest reduction in survival, possibly secondary to diminished radiation therapy efficacy.

The Health Utility and Valuation of Cosmetic Rhinoplasty.

Importance: The importance of this study is to understand the impact of rhinoplasty as perceived by society and to conceptualize the health utility metric of cosmetic rhinoplasty in relation to other health interventions. Objective: This novel study seeks to measure and quantify the health state utility and valuation of cosmetic rhinoplasty. Design, Setting, Participants: This is a cross-sectional survey administered through public online forums to 161 casual observers in America. Main Outcomes and Measures: Participants were shown pre- and postoperative photographs of six patients who underwent cosmetic rhinoplasty and two patients who did not undergo surgery. Observers were asked to imagine that the external nose in each image was on their own face and rated (1) their health state utility and (2) how much they were willing to pay (WTP) to have the ideal nose. Results: Established metrics of standard gamble and visual analog scale were explored in detail. Using these valuation and health utility data, we calculated WTP per quality-adjusted-life-year (WTP/QALY). The WTP/QALY for cosmetic rhinoplasty is $12,264 per QALY, which is significantly below cost-effective thresholds. Participants were willing to accept 10% risk of death to undergo cosmetic rhinoplasty. Conclusions and Relevance: Calculating WTP/QALY as a metric, we assess and quantify the social importance of rhinoplasty. This is the first study to demonstrate that elective cosmetic rhinoplasty can be a high-value intervention as perceived by society. Furthermore, the high percentage of risk of death that participants are willing to accept for cosmetic rhinoplasty suggests there is a profound psychosocial impact of external nasal deformity. These findings have implications for patients, surgeons, and health policy makers.

Normal Gaze Patterns of the Face in Lateral View.

Importance: Current efforts to quantify the attentional distraction of facial deformities have been limited to deformities that are best perceived when the face is in frontal view, and there remains a paucity of knowledge of societal perception of the face in lateral view. To date, no attempts have been made to characterize the fixation patterns of the face in lateral view. Objective: To characterize the fixation patterns and gaze patterns of the face in lateral view. Design, Setting, and Participants: This was a prospective randomized controlled trial at an academic tertiary medical center. Eighty participants (mean age 23.6 ± 1.7 years, 52.5% female) gazed freely at 11 images of faces in lateral view for 10 s each as an infrared eye-tracker recorded eye movements in real time. Main Outcomes and Measures: Recorded eye movements are superimposed on the images to visualize areas of interest (AOIs) that attract the most attention. Fixation duration targeted at each AOI is transformed into relative fixation of the entire face and neck. Hotelling's test of variance followed by post hoc t-testing assessed for the significance of fixation differences between the mouth and cheeks. Results: Participants spent an average of 6.0 (95% CI 5.8-6.2) s gazing at the face and neck areas of each image. Of this attention, 2.8 s or 49.8% (45.4-54.2%) was directed toward the eye, followed distantly by the nose (mean, 95% CI) (16.4%, 14.5-18.3%), cheek (12.0%, 11.4-14.5%), neck (4.6%, 3.8-5.4%), and mouth (4.0%, 3.4-4.6%). These differences were found to be significant by Hotelling's analysis and post hoc testing. A student's t-test also indicated observers directed significantly more attention within the eye-nose-cheek triangle [4.6 s or 79.5% (75.6-83.5)] compared with the eye-nose-mouth triangle [4.1 s or 71.2% (66.9-75.5)] (p < 0.001). Conclusions and Relevance: When perceiving novel faces in lateral view, casual observers preferentially directed attention toward the eye, nose, and cheek. These findings suggest that we draw from a slightly different collection of features to build a schema of the sagittal face, which may serve to complement the central triangle and build upon a three-dimensional model of the "normal" human face. Level of Evidence: NA.

How Old Do I Look? Exploring the Facial Cues of Age in a Tasked Eye-Tracking Study.

Importance: This is the first eye-tracking study to use a tasked age estimation paradigm to explore the facial cues of age as seen by casual observers. Objectives: Determine where observers gaze on faces when tasked with estimating an individual's age. Design, Setting, and Participants: This was a prospective controlled experiment, which took place at an academic tertiary referral center. In total, 220 casual observers (80 untasked, 140 tasked) viewed frontal facial images of women while an infrared eye-tracking monitor recorded their eye movements and fixations in real time. Main Outcomes and Measures: Multivariate Hotelling's analysis followed by planned posthypothesis testing was used to compare fixation durations for predefined regions of interest, including the central triangle, upper face, midface, lower face, and neck between tasked and untasked observers. Results: A total of 80 observers (mean age 23.6 years, 53% female) successfully completed the first untasked eye-tracking experiment. A total of 140 observers (mean age 26.1 years, 60% female) successfully completed the second age estimation experiment. On multivariate analysis, there were significant differences in the distribution of attention between observers in the two experiments (T2 = 99.70; F(5,2084) = 19.9012, p < 0.0001). On planned posthypothesis testing, observers attended significantly more to the lower third of the face (0.20 s, p < 0.0001, 95% confidence interval (CI) 0.14-0.27 s) and neck (0.05 s, p = 0.0074, 95% CI 0.01-0.08 s) and less to the upper third of the face (-0.27 s, p < 0.0001, 95% CI -0.40 to -0.14 s) when tasked. There was no significant difference in time spent on the whole face in the two experiments, suggesting that peripheral elements such as hair color or jewelry did not significantly influence gaze patterns. Conclusions and Relevance: Humans form judgments about others every day of their lives, and age perception colors their every interaction. To our knowledge, this study is the first to use eye tracking to investigate facial cues of age. The results showed that when tasked with estimating age, casual observer visual attention was shifted toward the lower face when compared with those who were untasked. These data inform our understanding of facial age perception and potential areas to target for facial rejuvenation. Level of Evidence: NA.