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Background: Hair restoration surgery (HRS) is a commonly performed elective procedure but to date lacks a review of the full scope of complications., Objectives: To provide a comprehensive overview of observed complications associated with follicular unit extraction (FUE) and follicular unit transplantation (FUT)., Eligibility Criteria: Randomized control trials, cohort studies, case series, and case reports published in 1985 or later on adults (age>18). Nontraumatic or autoimmune etiologies of alopecia were excluded as procedure indications., Sources of Evidence: PubMed, EMBASE, Cochrane databases (last search December 31, 2022)., Charting Methods: Data-charting and extraction were independently performed with two reviewers using Covidence., Results: Forty-three publications were included. Two large series reported the overall complication rate to be 1.2 and 4.7%. Common complications included bleeding requiring intervention (up to 8%), persistent numbness (up to 11%), infection (up to 11% with two reports of Kaposi varicelliform eruptions and one of mucormycosis), effluvium at donor and recipient sites (up to 4.1% and 6.5%, respectively). The most common donor-site complication was hypertrophic scarring/keloid formation after FUT (up to 15.1%). Complications at the recipient site, including crusting (up to 54.8%), frontal edema (up to 50%), and sterile folliculitis (up to 53.3%), tended to be poorly defined with a broad range of incidences., Conclusion: Serious complications associated with HRS are rare in the hands of experienced providers. However, comprehensive discussions of risk must be had with prospective patients as any complication in the context of an elective procedure may be significant and psychologically devastating for the individual patient., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Alopecia, a widespread issue affecting both genders, often manifests as androgenetic alopecia, although a thorough examination is needed to rule out other causes. This chapter focuses on the treatment of androgenetic alopecia. Finasteride and minoxidil, the Food and Drug Administration-approved treatments, offer stability and in some cases improvement in scalp coverage. Platelet-rich plasma exhibits positive results as an off-label alopecia therapy. For eligible individuals, hair transplantation proves effective, using healthy follicular units to restore hair-bearing areas. Multiple options allow for the tailoring of interventions to each patient., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Facial filler is emerging as a nonsurgical alternative for addressing static asymmetry in facial paralysis (FP). Objectives: To elucidate the patient experience for facial filler and to facilitate preprocedure counseling and education. Materials and Methods: Patients receiving hyaluronic acid filler for FP at a tertiary academic medical center were prospectively recruited. Primary outcomes included patient-reported pain, facial symmetry (on a visual analog scale), and the results of quality-of-life surveys (FACE-Q satisfaction with facial appearance [SFA], FACE-Q psychosocial distress [PSD], Patient Health Questionnaire-9 [PHQ-9], and Euro Quality of Life 5-Dimension [EQ5D]) preprocedure and at 1 and 14 days postprocedure. Results: Twenty patients (90% women, average age 55 ± 11) completed the study. Sites of filler included the cheek, lower lip, nasolabial fold, chin, and temple regions. Patients reported minimal pain at postprocedure days (PPDs) 1 and 14. Patient-perceived symmetry scores improved significantly ( p  < 0.0001), as did FACE-Q SFA and FACE-Q PSD scores ( p  < 0.0001, <0.0001) when comparing preprocedure with PPD 14. Depression, assessed by PHQ-9, and the anxiety/depression domain of EQ5D, decreased after treatment ( p  = 0.016, 0.014) but no change was observed in the other domains of EQ5D. Conclusion: Facial filler for FP can be performed with minimal morbidity (pain, impact on daily routine, and complications) and leads to improvements across multiple psychosocial domains.

Rhinoplasty is one of the most performed elective surgeries, and given the opioid crisis, increasing research and studies are focused on successful pain control with multimodality opioid-sparing techniques, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and gabapentin. Although limiting overuse of opioids is critical, this cannot be at the expense of inadequate pain control, particularly as insufficient pain control can be correlated with patient dissatisfaction and the postoperative experience in elective surgery. There is likely significant opioid overprescription, as patients often report taking less than 50% of their prescribed opioids. Furthermore, excess opioids provide opportunities for misuse and opioid diversion if not disposed of properly. To optimize postoperative pain control and minimize opioid requirements, interventions must occur at the preoperative, intraoperative, and postoperative time points. Preoperative counseling is imperative to set expectations for pain and to screen for predisposing factors for opioid misuse. Intraoperatively, use of local nerve blocks and long-acting analgesia in conjunction with modified surgical techniques can lead to prolonged pain control. Postoperatively, pain should be managed with a multimodal approach, incorporating acetaminophen, NSAIDs, and potentially gabapentin with opioids reserved for rescue analgesia. Rhinoplasty represents a category of short-stay, low/medium pain, and elective procedures highly susceptible to overprescription and consequently, are readily amenable to opioid minimization through standardized perioperative interventions. Recent literature on regimens and interventions to help limit opioids after rhinoplasty are reviewed and discussed here., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Little is known about pricing for reconstructive procedures of the head and neck. As of January 2021, the Centers for Medicare and Medicaid Services requires hospitals to disclose payer-negotiated prices for services, offering new insight into prices for privately insured patients., Study Design: Cross-sectional analysis., Setting: Turquoise database., Methods: Payer-negotiated facility fees for 41 reconstructive surgeries were grouped by procedure type: primary closure, skin grafts, tissue rearrangement, locoregional flaps, or free flaps. Prices were normalized to account for local labor costs, then calculated as percent markup in excess of Medicare reimbursement. The mean percent markup between procedure groups was compared by the Kruskal-Wallis test. Subset analyses were performed to compare mean percent markup using a Student's t test. We also assessed price variation by calculating the ratio of 90th/10th percentile mean prices both across and within hospitals., Results: In total, 1324 hospitals (85% urban, 81% nonprofit, 49% teaching) were included. Median payer-negotiated fees showed an increasing trend with more complex procedures, ranging from $379.54 (interquartile range [IQR], $230.87-$656.96) for Current Procedural Terminology (CPT) code 12001 ("simple repair of superficial wounds ≤2.5 cm") to $5422.60 ($3983.55-$8169.41) for CPT code 20969 ("free osteocutaneous flap with microvascular anastomosis"). Median percent markup was highest for primary closure procedures (576.17% [IQR, 326.28%-1089.34%]) and lowest for free flaps (99.56% [37.86%-194.02%]). Higher mean percent markups were observed for rural, for-profit, non-Northeast, nonteaching, and smaller hospitals., Conclusion: Wide variation in private payer-negotiated facility fees exists for head/neck reconstruction surgeries. Further research is necessary to better understand how pricing variation may correlate with out-of-pocket costs and quality of care., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Facial filler is an effective nonsurgical treatment option for improving facial symmetry in patients with facial paralysis (FP). Objective: To compare the effects of filler among patients with FP that is self-perceived as major or minor asymmetry, by measuring psychosocial distress. Methods: In this prospective cohort study of patients with FP undergoing filler at a tertiary academic center, patients were classified as having minor or major self-perceived asymmetry using a visual analog scale (VAS). FACE-Q Appearance-Related Psychosocial Distress was administered before and after filler. Descriptive statistics and a random-effects generalized linear model assessed the relationship between perceived facial asymmetry and change in psychosocial distress. Results: A total of 28 patients participated. Twenty-five (89%) patients were female with median age of 54 (interquartile range [IQR]: 49-66). Median VAS score was 2 (IQR: 1-3.5, 0 = completely asymmetric, 10 = no asymmetry). Psychosocial distress improved in all patients after filler. In multivariable modeling, patients with major asymmetry experienced 2.45 (confidence interval: 0.46-4.44, p  = 0.016) points more improvement in psychosocial distress than patients with minor asymmetry. Age, gender, and FP duration were not associated with change in psychosocial distress. Conclusion: Facial filler treatment was seen to improve psychosocial distress in patients with FP, especially by those with more self-perceived deficit.

Competing Interests: None

Competing Interests: The authors have disclosed no conflicts of interest.

Background: Hair loss causes significant psychosocial distress to patients. Health utility measurements offer an objective, quantitative assessment of health-related quality of life (QOL)., Methods: We performed a prospective cohort study on patients with hair loss between January 1, 2018 and December 31, 2020. Patient metrics were compared with layperson perception of alopecia, prospectively collected between August 1 and December 31, 2017. Health utility measures were quantified using the visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) in quality-adjusted life-years (QALYs) and relative to the minimal clinically important difference (MCID). Bonferroni correction to the significance threshold was performed., Results: Thirty-one patients with alopecia were compared with 237 laypeople. Patient metrics for female hair loss were all significantly lower than laypeople measures (VAS QALYs 0.65 ± 0.21 vs. 0.83 ± 0.18, p = 0.0001). Mean SG QALYs were lower for patients in the male alopecia state (0.86 ± 0.23 vs. 0.96 ± 0.12, p = 0.0278). Post-hair transplant improvement in TTO was significantly greater for patients (+ 0.08 ± 0.12 vs. + 0.02 ± 0.09, p = 0.0070) and significantly more often exceeded the MCID (45.2% vs. 16.9%, p = 0.0006)., Conclusions: Alopecia negatively impacts QOL, and the true patient experience is more taxing than what is perceived by laypeople. Hair transplantation improves QOL more for male patients than common perception., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine., (© 2023. The Author(s).)

Protein acetylation plays a key role in regulating cellular processes and is subject to aberrant control in diverse pathologies. Although histone deacetylase (HDAC) inhibitors are approved drugs for certain cancers, it is not known whether they can be deployed in other therapeutic contexts. We have explored the clinical HDAC inhibitor, zabadinostat/CXD101, and found that it is a stand-alone regulator of the adaptive immune response. Zabadinostat treatment increased expression of MHC class I and II genes in a variety of cells, including dendritic cells (DCs) and healthy tissue. Remarkably, zabadinostat enhanced the activity of DCs, and CD4 and CD8 T lymphocytes. Using an antigenic peptide presented to the immune system by MHC class I, zabadinostat caused an increase in antigen-specific CD8 T lymphocytes. Further, mice immunised with covid19 spike protein and treated with zabadinostat exhibit enhanced covid19 neutralising antibodies and an increased level of T lymphocytes. The enhanced humoral response reflected increased activity of T follicular helper (Tfh) cells and germinal centre (GC) B cells. Our results argue strongly that zabadinostat has potential to augment diverse therapeutic agents that act through the immune system., (© 2023. The Author(s).)

Virus-based tumour vaccines offer many advantages compared to other antigen-delivering systems. They generate concerted innate and adaptive immune response, and robust CD8 + T cell responses. We engineered a non-replicating pseudotyped influenza virus (S-FLU) to deliver the well-known cancer testis antigen, NY-ESO-1 (NY-ESO-1 S-FLU). Intranasal or intramuscular immunization of NY-ESO-1 S-FLU virus in mice elicited a strong NY-ESO-1-specific CD8 + T cell response in lungs and spleen that resulted in the regression of NY-ESO-1-expressing lung tumour and subcutaneous tumour, respectively. Combined administration with anti-PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen-specific CD8 + T cell response and protection against tumour development in combination with PD-1 blockade., Competing Interests: MK, UG, PR, TT, LL, JC, GP, PK, AT, VC No competing interests declared, (© 2023, Kandasamy et al.)

Introduction: The use of computed tomography (CT) in healthcare institutions has increased rapidly in recent years. The Singapore Health Services (SingHealth) cluster of healthcare institutions has taken the first step in establishing a local cluster-wide CT Diagnostic Reference Levels (DRL) in Singapore. CT dose data from each institution were collected through two primary dosimetry metrics: volume CT dose index (CTDI vol measured in mGy) and dose-length product (DLP measured in mGy.cm)., Methods: Data from 19 CT scanners in seven institutions under one of Singapore healthcare cluster were retrospectively collected and analysed. The five common adult CT examinations analysed were CT Brain (non-contrast enhanced), CT Chest (IV contrast enhanced), CT Kidney-Ureter-Bladder (CT KUB, non-contrast enhanced), CT Pulmonary Angiogram (CT PA, IV contrast enhanced) and CT Abdomen-Pelvis (CT AP, IV contrast enhanced, single phase). Median CTDI vol and DLP values for the five CT examinations from each institution were derived, with the cluster DRLs determined as the 75th percentile of the distribution of the institution median dose values., Results: A total of 2413 dose data points were collected over a six-month period from June to November 2020. The cluster CT DRLs for the five CT examinations were determined to be 47 mGy and 820 mGy.cm for CT Brain, 5.4 mGy and 225 mGy.cm for CT Chest, 6.7 mGy and 248 mGy.cm for CT PA, 4.6 mGy and 190 mGy.cm for CT KUB and 6.9 mGy and 349 mGy.cm for CT AP., Conclusion: The establishment of the cluster CT DRLs provided individual institutions with a better understanding if their CT doses are unusually high or low, while emphasising that these DRLs are not meant as hard dose limits or constraints to follow strictly., Competing Interests: Conflict of interest statement All authors have no conflict of interest to declare., (Copyright © 2022 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

This study aims at identifying characteristics, risk factors and mortality of community-acquired (CAP) and health-care-associated pneumonia (HCAP) by Staphylococcus aureus (S. aureus). We retrieved adults with S. aureus CAP or HCAP diagnosed by blood or pleural effusion culture in 2.6 years, and compared with those of Streptococcus pneumoniae (S. pneumoniae) CAP or HCAP diagnosed by blood or respiratory culture, or urine antigen. We found 18 patients with CAP and 9 HCAP due to S. aureus (female 33%, 66.6 ± 12.4 years-old), and 48 patients with CAP and 15 HCAP due to S pneumoniae (female 41%, 69.5 ± 17.5 years). Diabetes mellitus (52% vs. 24%, p = 0.019), hemodialysis (11% vs. 0%, p = 0.046), skin lesions (44% vs. 0%, p < 0.001), cavitary nodules (37% vs. 1.6%, p < 0.001) and pleural effusions (48% vs. 18%, p = 0.007) were more common in staphylococcal than pneumococcal group. Three patients with staphylococcal pneumonia had acute myocardial infarction. Pneumonia severity index (139 ± 52 vs. 109 ± 43, p = 0.005) and 30-day mortality (41% vs. 9.5%, p = 0.001) were higher in staphylococcal group. Multivariate analysis showed underlying disease (especially cancer and cirrhosis), risk class 4/5, altered mentality, shock and bilateral pneumonia were risk factors for 30-day mortality., (© 2022. The Author(s).)

The cardinal electrophysiological signs in Parkinson's disease (PD) include augmented beta oscillations in the motor cortex-subthalamic nucleus (MC-STN) axis and excessive burst discharges in STN. We have shown that excessive STN burst discharges have a direct causal relation with the locomotor deficits in PD. To investigate the correlation between the two cardinal signs, we characterized the courses of development of the electrophysiological abnormalities in the hemiparkinsonian rat model. The loss of dopaminergic neurons develops fast, and is histologically completed within 4-7 days of the lesion. The increase in STN burst discharges is limited to the lesioned side, and follows a very similar course. In contrast, beta augmentation has a bilateral presentation, and requires 14-21 days for full development. Behaviorally, the gross locomotor deficits in open field test and limb akinesia in stepping test match the foregoing fast and slow time courses, respectively. A further look into the spike entrainment shows that the oscillations in local field potential (LFP) of the MC effectively entrain the multi-unit (MU) spikes of MC, STN and entopeduncular nucleus (EPN), a rat homolog of human globus pallidus interna (GPi), whereas the LFP of STN or EPN (GPi) cannot entrain the spikes in MC. We conclude that excessive STN burst discharges are a direct consequence, whereas beta augmentation is probably a secondary or adaptive changes in the cortico-subcortical re-entrant loops, to dopaminergic deprivation. Beta augmentation is therefore not so consistently present as excessive STN burst discharges, but could signal more delicate derangements at the level of cortical programming in PD., (Copyright © 2022. Published by Elsevier Inc.)

Background: Mental health issues among emerging adults (aged 19-25 years) on a global scale have underscored the need to address their widespread experiences of depression and anxiety. As a result of the COVID-19 pandemic, emerging studies are being directed toward the development and deployment of digital peer emotional disclosure and support for the psychological well-being of emerging adults. However, it is important to explore the implementation and clinical effectiveness, as well as associated mechanisms of change, for optimal approaches in conducting digital peer support interventions for emerging adults' psychological well-being., Objective: We describe a randomized controlled trial to evaluate the implementation and clinical effectiveness of Acceset, a digital peer support intervention to address emerging adult mental well-being. The intervention has 2 components. First, the digital peer support training equips befrienders (ie, peers who provide support) to harness 4 components of psychological well-being-mattering, selfhood, compassion, and mindfulness-to provide effective peer support for seekers (ie, peers who seek support). Second, Acceset incorporates psychological well-being digital markers and harnesses community engagement to drive emotional disclosure among peers., Methods: A total of 100 participants (aged 19-25 years) from the National University of Singapore will be recruited and randomized into 2 arms. In arm 1 (n=50), the seekers will use Acceset with befrienders (n=30) as well as moderators (n=30) for 3 weeks. Arm 2 comprises a wait-listed control group (n=50). A questionnaire battery will be used to monitor seekers and befrienders at 4 time points. These include baseline (before the intervention), 3 weeks (end of the intervention), and 6 and 9 weeks (carryover effect measurement). Implementation outcomes of the intervention will involve evaluation of the training curriculum with respect to adoption and fidelity as well as user acceptability of the Acceset platform and its feasibility for broader deployment. Clinical outcomes will include mattering, selfhood, compassion, mindfulness, perceived social support, and psychological well-being scores., Results: This protocol received National University of Singapore Institutional Ethics Review Board approval in October 2021. Recruitment will commence in January 2022. We expect data collection and analyses to be completed in June 2022. Preliminary findings are expected to be published in December 2022. The Cohen d index will be used for effect size estimation with a .05 (95% reliability) significance level and 80% power., Conclusions: This protocol considers a novel digital peer support intervention-Acceset-that incorporates components and digital markers of emerging adult mental well-being. Through the validation of the Acceset intervention, this study defines the parameters and conditions for digital peer support interventions for emerging adults., Trial Registration: ClinicalTrials.gov NCT05083676; https://clinicaltrials.gov/ct2/show/NCT05083676., International Registered Report Identifier (irrid): PRR1-10.2196/34602., (©GeckHong Yeo, Weining Chang, Li Neng Lee, Matt Oon, Dean Ho. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 20.09.2022.)

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.

The success of deep brain stimulation (DBS) therapy indicates that Parkinson's disease is a brain rhythm disorder. However, the manifestations of the erroneous rhythms corrected by DBS remain to be established. We found that augmentation of α rhythms and α coherence between the motor cortex (MC) and the subthalamic nucleus (STN) is characteristically prokinetic and is decreased in parkinsonian rats. In multi-unit recordings, movement is normally associated with increased changes in spatiotemporal activities rather than overall spike rates in MC. In parkinsonian rats, MC shows higher spike rates at rest but less spatiotemporal activity changes upon movement, and STN burst discharges are more prevalent, longer lasting, and less responsive to MC inputs. DBS at STN rectifies the foregoing pathological MC-STN oscillations and consequently locomotor deficits, yet overstimulation may cause behavioral restlessness. These results indicate that delicate electrophysiological considerations at both cortical and subcortical levels should be exercised for optimal DBS therapy., (© 2022. The Author(s).)

Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatment of patients with chronic obstructive pulmonary disease (COPD). To evaluate the efficacy of HFNC, impulse oscillation system (IOS) is a new noninvasive technique in measuring the impedance of different portions of lungs. It shows higher sensitivity in contrast to conventional pulmonary function tests (PFT). However, whether IOS is an appropriate technique to evaluate the efficacy of HFNC in improving the impedance of small airways or peripheral lung in patients with COPD is still unclear. We enrolled 26 stable COPD participants randomised into two groups receiving HFNC or nasal cannula (NC) for 10 min followed by a 4-week washout period and crossover alternatively. IOS was used to detect the difference of respiratory impedance after HFNC or NC interventions. IOS parameters, PFT results, transcutaneous partial pressure of carbon dioxide, peripheral oxygen saturation, body temperature, respiratory rate, pulse rate, and blood pressure at the time of pre-HFNC, post-HFNC, pre-NC, and post-NC, were collected and analysed using SPSS (version 25.0, IBM, Armonk, NY, USA). The IOS measurement indicated that HFNC significantly improved R5, R5% predicted, R5-R20, X5-predicted, and Fres compared with NC, whereas no significant difference was observed through the PFT measurement. The beneficial effect of HFNC in improving small airway resistance and peripheral lung reactance compared with that of NC in patients with stable COPD was confirmed through IOS measurement.Trial registration: ClinicalTrials.gov NCT05130112 22/11/2021., (© 2022. The Author(s).)

Objectives/hypothesis: Dermal filler (DF) is a widely used nonsurgical option for facial rejuvenation with a rapidly expanding market. Physician payments by DF industry leaders have yet to be characterized. We sought to investigate trends in physician-industry payments by DF companies over 6 years. Differences in payments based on physician specialty and time were characterized., Study Design: Database review., Methods: The Open Payments Database was queried from 2013 to 2018. Payments made by the three largest DF companies by market share to otolaryngologists, plastic surgeons, and dermatologists were analyzed. Total dollars paid, number of payments made, type of payments made, and total number of specialists paid were recorded. One-way ANOVA was used for statistical analysis., Results: Otolaryngologists, plastic surgeons, and dermatologists received average annual payments of $0.36 million, $6.3 million, and $6.6 million respectively (P < .001). An average of 330 otolaryngologists, 2,128 plastic surgeons, and 5,980 dermatologists were paid annually (P < .001). Accredited speaking arrangements, consulting fees, and royalty/licensing fees comprised the majority of dollars paid to physicians., Conclusions: Average physician payment by DF companies exceeds $12 million annually, with otolaryngologists receiving significantly less compared to plastic surgeons and dermatologists., Level of Evidence: NA Laryngoscope, 132:301-306, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Parkinson's disease (PD), or paralysis agitans, is a common neurodegenerative disease characterized by dopaminergic deprivation in the basal ganglia because of neuronal loss in the substantia nigra pars compacta. Clinically, PD apparently involves both hypokinetic (e.g. akinetic rigidity) and hyperkinetic (e.g. tremor/propulsion) symptoms. The symptomatic pathogenesis, however, has remained elusive. The recent success of deep brain stimulation (DBS) therapy applied to the subthalamic nucleus (STN) or the globus pallidus pars internus indicates that there are essential electrophysiological abnormalities in PD. Consistently, dopamine-deprived STN shows excessive burst discharges. This proves to be a central pathophysiological element causally linked to the locomotor deficits in PD, as maneuvers (such as DBS of different polarities) decreasing and increasing STN burst discharges would decrease and increase the locomotor deficits, respectively. STN bursts are not so autonomous but show a "relay" feature, requiring glutamatergic synaptic inputs from the motor cortex (MC) to develop. In PD, there is an increase in overall MC activities and the corticosubthalamic input is enhanced and contributory to excessive burst discharges in STN. The increase in MC activities may be relevant to the enhanced beta power in local field potentials (LFP) as well as the deranged motor programming at the cortical level in PD. Moreover, MC could not only drive erroneous STN bursts, but also be driven by STN discharges at specific LFP frequencies (~ 4 to 6 Hz) to produce coherent tremulous muscle contractions. In essence, PD may be viewed as a disorder with deranged rhythms in the cortico-subcortical re-entrant loops, manifestly including STN, the major component of the oscillating core, and MC, the origin of the final common descending motor pathways. The configurations of the deranged rhythms may play a determinant role in the symptomatic pathogenesis of PD, and provide insight into the mechanism underlying normal motor control. Therapeutic brain stimulation for PD and relevant disorders should be adaptively exercised with in-depth pathophysiological considerations for each individual patient, and aim at a final normalization of cortical discharge patterns for the best ameliorating effect on the locomotor and even non-motor symptoms., (© 2021. The Author(s).)

Objective: To evaluate opioid prescribing patterns among American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS) members in the Medicare population. Methods: Retrospective cohort study of AAFPRS members in the Medicare Part D Prescriber dataset. Results: From 2014 to 2016, there was a significant decrease in the number of days of opioids supplied per beneficiary (5.9 vs. 4.9 days, p  < 0.005), as well as the opioid prescription cost per beneficiary ($14.52 vs. $11.79, p  = 0.005). The highest prescription rate was found in the Midwest (20.5%) and lowest in the Northeast (14.0%), however, the difference between geographic regions was not significant ( p  = 0.11). There was a significant decrease in the number of total opioid days supplied per beneficiary in the South ( p  = 0.001), Midwest ( p  = 0.05), and West regions ( p  < 0.001). There was no significant difference in opioid prescription rate ( p  = 0.89) or total opioid days supplied per beneficiary ( p  = 0.26) when states were stratified by age-adjusted opioid-specific death rate. Conclusion: This study demonstrates a national trend toward fewer opioid days supplied and less opioid cost per Medicare beneficiary among AAFPRS members between 2014 and 2016.

Effluent discharge from wastewater treatment plants can be a substantial source of microplastics in receiving water bodies including rivers. Despite growing concern about microplastic pollution in freshwater habitats, the literature has not yet addressed effluent-dependent rivers, which derive 100% of their baseflow from effluent. The objective of this study was to document and explore trends in microplastic pollution within the effluent-dependent lower Santa Cruz River near Tucson, Arizona (USA). We examined microplastic concentrations in the water column and benthic sediment and microplastic consumption by mosquitofish (Gambusia affinis) at 10 sites along a ~40 km stretch of the lower Santa Cruz River across two time periods: baseflow (effluent only) and post-flood (effluent immediately following urban runoff). In total, across both sampling periods, we detected microplastics in 95% of water column samples, 99% of sediment samples, and 6% of mosquitofish stomachs. Flow status (baseflow vs post-flood) was the only significant predictor of microplastic presence and concentrations in our models. Microplastic fragment concentrations in the water column were higher post-flood, microplastic fiber concentrations in benthic sediment were lower post-flood, and mosquitofish were more likely to have consumed microplastics post-flood than during baseflow. The additional microplastics detected after flooding was likely due to a combination of allochthonous material entering the channel via runoff and bed scour that exhumed microplastics previously buried in the riverbed. Effluent-dependent urban streams are becoming increasingly common; more work is needed to identify microplastic pollution baselines and trends in effluent rivers worldwide., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Gender-affirming surgery may be pursued by individuals experiencing gender dysphoria. Although genital and chest procedures are classified as medically necessary, facial feminization surgeries (FFSs) are often considered cosmetic. Insurance companies may limit coverage of these procedures, especially in states less supportive of transgender individuals. Objectives: To determine insurance coverage and ease of finding policy information for FFSs, and to analyze differences based on state advocacy. Methods: Insurance policies for the top three commercial health plans per state were reviewed. Coverage status was determined by web-based search and telephone interviews. Ease of gathering policy information was assessed using a post-task questionnaire graded on a 7-point Likert scale, with higher numbers (e.g., 7) representing relative ease. State advocacy was determined by the number of state laws and policies affecting the transgender community. Results: Of the 150 insurance policies, only 27 (18%) held favorable policies for FFS. Most favorable companies covered chondrolaryngoplasty, with 78% ( n  = 21) offering preauthorization. Mean ease of use was rated 6, with 12 companies requiring a telephone interview. Insurance policies in states with laws driving transgender equity covered more FFS procedures ( p  = 0.043), whereas those in restrictive states offered less overall coverage ( p  = 0.023). Conclusions: FFS is rarely covered by commercial insurance companies, especially in states with less legal support for transgender individuals. Policy information remains difficult to obtain, with variable coverage by employer and no standardized medical necessity criteria. Limited coverage, lack of easily accessible information, and absence of universal criteria may act as barriers to FFS.

Moderate angle cutting maneuvers (between 45º and 90º) are common and essential performance skills for success in multidirectional sports. Research addresses the injury risks of cutting but few studies have attempted to quantify the performance of the cut itself., Purpose: To identify any anthropometric, kinematic, and/or kinetic markers of a high-performance cut so they may be taught and lead to more effective training., Methods: Ten college-aged male athletes (mass 73.97 ± 8.77kg, height 1.81 ± 0.07m) and ten non-athletes (mass 87.37 ± 13.93kg, height 1.85 ± 0.04m) completed five moderate angle cutting trials with a speed constraint of 4.03 m/s - 4.44 m/s through a 3 m in to and 3 m out of a 60° change in direction set-up. Kinetic and kinematic measurements were recorded through ground reaction forces and lower limb angles., Results: A Bonferroni correction revealed that athletes spent significantly less time in the propulsion phase (52.0% ± 0.02%, p < 0.02) compared to non-athletes (55.4% ± 0.03%, p < 0.02). The propulsion phase was determined as the percentage of the contact phase the knee was extending (e.g. Green, et al, 2012). The athletes produced significantly greater instantaneous values of X GRF, Y GRF, and Z GRF during the propulsion phase ( p < .05)., Conclusion: Greater GRFs coupled with shorter propulsion phases by the athletes accounted for the lack of differences in the propulsion impulse between the two groups. Changing direction in a shorter time improves an athlete's ability to evade an opponent, by decreasing the time an opponent has to react to a new direction.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Adenoviral vectors emerged as important platforms for cancer immunotherapy. Vaccination with adenoviral vectors is promising in this respect, however, their specific mechanisms of action are not fully understood. Here, we assessed the development and maintenance of vaccine-induced tumor-specific CD8 + T cells elicited upon immunization with adenoviral vectors., Methods: Adenoviral vaccine vectors encoding the full-length E7 protein from human papilloma virus (HPV) or the immunodominant epitope from E7 were generated, and mice were immunized intravenously with different quantities (10 7 , 10 8 or 10 9 infectious units). The magnitude, kinetics and tumor protection capacity of the induced vaccine-specific T cell responses were evaluated., Results: The adenoviral vaccines elicited inflationary E7-specific memory CD8 + T cell responses in a dose-dependent manner. The magnitude of these vaccine-specific CD8 + T cells in the circulation related to the development of E7-specific CD8 + tissue-resident memory T (T RM ) cells, which were maintained for months in multiple tissues after vaccination. The vaccine-specific CD8 + T cell responses conferred long-term protection against HPV-induced carcinomas in the skin and liver, and this protection required the induction and accumulation of CD8 + T RM cells. Moreover, the formation of CD8 + T RM cells could be enhanced by temporal targeting CD80/CD86 costimulatory interactions via CTLA-4 blockade early after immunization., Conclusions: Together, these data show that adenoviral vector-induced CD8 + T cell inflation promotes protective T RM cell populations, and this can be enhanced by targeting CTLA-4., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In an era of widespread Internet access, patients increasingly look online for health information. Given the frequency with which cosmetic botulinum toxin injection is performed, there is a need to provide patients with high-quality information about this procedure., Objectives: The aim of this study was to examine the quality of printed online education materials (POEMs) about cosmetic botulinum toxin., Methods: An Internet search was performed to identify 32 websites of various authorship types. Materials were evaluated for accuracy and inclusion of key content points. Readability was measured by Flesch Reading Ease and Flesch-Kincaid Grade Level. Understandability and actionability were assessed with the Patient Education Materials Assessment Tool for Printed Materials. The effect of authorship was measured by undertaking analysis of variance between groups., Results: The mean [standard deviation] accuracy score among all POEMs was 4.2 [0.7], which represents an accuracy of 76% to 99%. Mean comprehensiveness was 47.0% [16.4%]. Mean Flesch-Kincaid Grade Level and Flesch Reading Ease scores were 10.7 [2.1] and 47.9 [10.0], respectively. Mean understandability and actionability were 62.8% [18.8%] and 36.2% [26.5%], respectively. There were no significant differences between accuracy (P > 0.2), comprehensiveness (P > 0.5), readability (P > 0.1), understandability (P > 0.3), or actionability (P > 0.2) by authorship., Conclusions: There is wide variability in the quality of cosmetic botulinum toxin POEMs regardless of authorship type. The majority of materials are written above the recommended reading level and fail to include important content points. It is critical that providers take an active role in the evaluation and endorsement of online patient education materials., (© 2020 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019.ResultsAll samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5-6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic.ConclusionAlthough blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak.

Objectives: Chronic pulmonary aspergillosis (CPA) is an emerging global disease with tuberculosis (TB) being the most important risk factor. Epidemiologic data on the seroprevalence of Aspergillus IgG and prevalence of CPA in different areas, especially in country with intermediate burden of TB, are lacking., Methods: We prospectively recruited healthy volunteers, TB close contacts, active TB patients and participants with old pulmonary TB in Taiwan during 2012-2019. We measured serum Aspergillus fumigatus and niger-specific IgG levels and assessed if the participants were having CPA., Results: A total of 1242 participants (including 200 healthy volunteers, 326 TB close contacts, 524 active TB patients and 192 old TB cases) were recruited. Using 27 mgA/L (milligrams of antigen-specific antibodies per liter) as cut-off level, the seropositive rate of A. fumigatus-specific IgG was 33.0% (66/200), 37.7% (123/326), 26.5% (139/524) and 43.2% (83/192) among the four groups, respectively. In multivariate logistic regression, pulmonary cavitation (OR 1.73; 95% CI 1.07-2.80), female sex (OR 1.49; 95% CI 1.14-1.95), old TB (OR 1.59; 1.05-2.42) were independent risk factors for Aspergillus IgG positivity. One (0.2%) active TB patient and four (2.1%) old TB patients developed CPA. Correlation between A. fumigatus and A. niger-specific IgG was high (Spearman correlation coefficient: 0.942)., Discussion: Geographic variation in Aspergillus IgG seroprevalence and CPA prevalence exists. A universal cut-off value for Aspergillus IgG may not exist. In areas and populations in which background Aspergillus IgG level is unknown, Aspergillus IgG may be better used as a test of exclusion for CPA using prespecified cut-off level., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: The SARS-CoV-2 coronavirus pandemic, referred to as COVID-19, has spread throughout the globe since its first case in China in December 2019, leaving a significant number of people infected and clinically ill. The purpose of this review is to provide the current known clinical characteristics of and management for COVID-19 as it relates to otolaryngology., Recent Findings: COVID-19 is a highly transmissible respiratory disease with common presenting symptoms of fever, cough, and fatigue. In the absence of available vaccines or antiviral therapies, symptomatic and respiratory support is the current standard of therapy. Measures to prevent further transmission have been enacted globally including social distancing and cancellation of public events. Given elevated viral load in the upper aerodigestive tract, extra precautions in patients with otolaryngology needs have been recommended for protection of both healthcare workers and patients., Summary: Otolaryngologists face unique risk from COVID-19. Maintaining appropriate preventive health measures and remaining updated on institutional clinical guidelines is paramount for both caretaker safety and patient care.

Objectives: Advanced nasal malignancies may require rhinectomy, which can have profound psychosocial impacts. Rhinectomy defects can be rehabilitated through surgery or prosthetics. We seek to understand the health utility of the rhinectomy defect, surgical, and prosthetic reconstruction, which have not been previously studied., Study Design: Prospective clinical study METHODS: Adult naïve observers (n = 273) ranked the utility of five randomized health states (monocular blindness, binocular blindness, post-rhinectomy nasal defect, postsurgical reconstruction, and post-prosthetic rehabilitation). Health utilities were measured using visual analogue scale (VAS), standard gamble (SG), and time trade-off (TTO). One-way analysis of variance (ANOVA) with post hoc Scheffe's test and the independent samples T-test for a priori comparisons were performed. Multiple linear regression was performed using participant demographics as independent predictors of utility scores., Results: Health utilities (VAS, SG, TTO) were reported as follows (mean ± SD): monocular blindness (0.71 ± 0.21, 0.84 ± 0.20, 0.85 ± 0.19), binocular blindness (0.48 ± 0.25, 0.68 ± 0.28, 0.63 ± 0.28), post-rhinectomy nasal defect (0.59 ± 0.24, 0.74 ± 0.24, 0.74 ± 0.24), postsurgical reconstruction (0.88 ± 0.16, 0.90 ± 0.18, 0.89 ± 0.13), and post-prosthetic rehabilitation (0.67 ± 0.22, 0.80 ± 0.23, 0.82 ± 0.20). Both surgical reconstruction (P < .001) and prosthetic rehabilitation (P < .001) significantly improved health utility. SG and TTO utility scores were inversely associated with observer age (P < .001) and participants who identified themselves as non-Caucasians (P < .05) in post-rhinectomy nasal defect, post-nasal surgical reconstruction, and post-nasal prosthetic rehabilitation health states, while higher levels of education were directly associated with SG scores (P < .05), respectively., Conclusion: This is the first study to demonstrate the significant negative impact of the rhinectomy nasal defect on health utility. Rehabilitation by surgical or prosthetic techniques significantly increases health utility as rated by naïve observers. Laryngoscope, 130:1674-1679, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: In the care of the facial paralysis (FP) patient, outcomes have historically focused on facial function rather than the psychosocial burden of the disease state. Yet, FP patients often describe the impact of their disease on domains of psychosocial health. These patient concerns have motivated clinicians to formally recognize and treat nonfunctional sequelae of the disease. Dermal filler therapy (DFT) is a minimally invasive reversible procedure that can be used to treat facial asymmetry and improve psychosocial well-being in FP patients. However, there are no data describing outcomes of DFT in FP-related facial asymmetry. Therefore, we sought to formally characterize FP patients' facial symmetry and psychosocial well-being before and after DFT. Methods: FP patients presenting for DFT at a tertiary academic medical center were prospectively interviewed. Patients completed the validated FACE-Q for Appearance-Related Psychosocial Distress instrument. Self-reported facial symmetry scores were recorded. Patients were evaluated before and 2 weeks after DFT. Statistical analysis was performed on R software using paired sample t -tests. Results: Twenty FP patients completed DFT treatment and two surveys. The cohort was predominantly female ( n  = 19, 95%) with an average age of 54 years. After a single treatment of DFT averaging 2.3 mL, patients had significant improvement in facial symmetry and psychosocial well-being. Patients felt particular improvement in self-confidence and emotional expression ( p  < 0.0001 for all stated comparisons). Conclusion: FP of varying etiologies is associated with significant functional, psychosocial, and quality-of-life impairments. This is the first prospective study to demonstrate statistically significant improvements in facial symmetry and psychosocial well-being after a single office-based treatment of dermal filler. In addition, our study's emphasis on psychosocial health instruments reflects an increased awareness of this important domain in the care of the FP patient.

Background: Understanding the multidimensional postoperative patient experience after rhinoplasty is critical for preoperative counseling and postoperative management. Methods: A prospective clinical study was conducted from June to December 2019 for 60 patients undergoing cosmetic and/or functional rhinoplasty by two facial plastic surgeons. All patients were administered the brief pain inventory, a clinically validated pain instrument, including multiple quality of life (QOL) domains, survey at postoperative days (PODs) 1, 2, 3, and 8. Nasal Obstruction Symptom Evaluation (NOSE) scores were used to predict patients having greatest QOL disturbance. Primary outcomes were postoperative QOL domains, pain scores, and oxycodone usage. Statistical analysis was performed using STATA 14.0 (STATA Corp., College Station, TX). Preoperative NOSE and postoperative Euro Quality of Life 5-Dimension scores were also recorded. Results: Patients showed greatest disruption to QOL in the first 3 PODs and essentially returned to normal levels by POD8, which mirrored trends in pain and opioid usage. All tested QOL domains (general activity, sleep, work, mood, enjoyment, and relationships) were strongly correlated with overall pain. NOSE scores were not significantly associated with pain or QOL impairment. Conclusions: This is the first study to prospectively evaluate the rhinoplasty patient's postoperative experience using a pain instrument, including multiple QOL domains. Utilizing a validated clinical instrument allows for standardized comparison of postrhinoplasty pain and QOL disruption with other surgical procedures and disease processes. These data may help guide preoperative counseling and set accurate patient expectations for the postoperative period.

Platelet-rich plasma (PRP) is a promising treatment for hair restoration in patients with androgenic alopecia. Created from a platelet concentrate from an autologous blood draw, PRP is a safe therapeutic option for patients with hair loss. It is used alone or in conjunction with topical and oral therapies. Most studies of hair restoration with PRP report positive outcomes. Further research to optimize PRP preparation/administration procedures and identify patient populations that benefit most from this treatment are needed, as is long-term follow-up of objective hair loss outcomes. PRP appears to be a safe technology with excellent potential for promoting hair restoration., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Facial analysis is a foundational aspect of facial plastic and reconstructive surgery. Unfortunately, ideal proportions of beauty are commonly discussed without much thought regarding their historical derivation and associated cultural implications. Facial analysis often is limited to narrow ethnic and gender-normative aesthetics. As we evolve as a specialty that treats disparate patient populations and embraces a diverse community of surgical trainees, it may be time to reframe our approach to facial analysis education.