The Influence of Mallet Mass and Velocity on the Fracture Patterns in Osteotomies.

INTRODUCTION: Osteotomies are routinely incorporated in rhinoplasty, however, the influence of mass, velocity, kinetic energy (KE), and momentum (p) of the mallet on fracture patterns has not been studied. METHODS: An experimental sledge guillotine setup was designed simulating a mallet strike with adjustable height and mass and 2 mm-thick Sawbone blocks. KE and p were calculated using KE = ½ mass × velocity2 and p = mass × velocity formulas. Fracture lengths and angles were measured. RESULTS: Ten groups with varying mallet masses and drop heights were tested with 10 bones per group. Fracture length positively correlated with KE (R = 0.542, p < 0.001) and p (R = 0.508, p < 0.001). Fracture angle also positively correlated with KE (R = 0.367, p < 0.001) and p (R = 0.329, p < 0.001). In groups with similar KE, osteotomies with higher p (heavier mallet with slower velocity) had greater fracture lengths (29.31 ± 0.68 vs. 27.68 ± 2.12 mm, p = 0.013) but similar fracture angles (p = 0.189). In groups with similar p, osteotomies with higher KE (lighter hammer with faster velocity) had significantly greater fracture lengths (28.28 ± 1.28 vs. 20.45 ± 12.20 mm, p = 0.041) and greater divergent fracture angles (3.13 ± 1.97° vs. 1.40 ± 1.36°, p = 0.031). Regression modeling of the relationship between KE and fracture lengths and angles demonstrated that cubic followed by logarithmic regression models had the best fits. CONCLUSION: Osteotomy fracture patterns positively correlated with the mallet's KE more so than its p, suggesting that the mallet's velocity has an increased impact effect than its mass. Clinically, a heavier mallet with a lower velocity will likely generate a smaller fracture length and fracture angle, indicating a more controlled and ideal fracture. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Impact of Tissue Handling and Size Modification on Septal Chondrocyte Viability.

INTRODUCTION: The physical modification of cartilage grafts during rhinoplasty risks chondrocyte death at the margins where the tissue is cut. This study compares chondrocyte viability between diced, scaled, and pate samples in human models, and further computes percent chondrocyte viability as a function of sequential dicing size in a computational model. METHODS: Septal cartilage from 11 individuals was prepared as follows: diced (1 mm cubic), scaled (shaved to <1 mm thickness ~ translucent), pate (0.02 g of scraped cartilage surface), positive control (2 × 2 mm diced), and negative control (2 × 2 mm diced soaked in 70% EtOH). Viability analysis was performed using Live/Dead assay™ and confocal microscopy. Numerical simulation of cartilage dicing in 0.05 mm increments was performed using MATLAB assuming 250 chondrocytes/mm3 with each average chondrocyte size of 65 µm2. RESULTS: Chondrocyte viability was similar between 1 mm diced cartilage, scaled cartilage, and positive control samples (p > 0.05). Conversely, pate samples had significantly less viability compared to positive controls, diced samples, and scaled samples (all p < 0.01 after Bonferroni correction). Pate samples had similar chondrocyte viability compared to negative controls (p = 0.36). On computational modeling, cartilage viability decreased to 50% as the diced sample was cut from 1 mm edge length to 0.7-0.8 mm. Similarly, cartilage viability decreased to 26% at 0.55-0.65 mm, 11% at 0.4-0.5 mm, and <5% at <0.4 mm edge length. CONCLUSION: Modifying septal cartilage grafts into 1 mm diced or scaled samples maintains ideal chondrocyte viability whereas pate preparations result in significant chondrocyte death. According to computational analysis, chondrocyte viability sharply decreases as the cartilage is diced below 0.7-0.8 mm. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

How Variable are Patient Comorbidity Profiles Among Practicing Otolaryngologists?

OBJECTIVE: To determine whether certain groups of otolaryngologists (ORLs) are treating cohorts of patients with more comorbidities. STUDY DESIGN: Cross-sectional population-based analysis. SETTING: 2019 Medicare Provider Utilization and Payment Dataset. METHODS: Each ORL's average Medicare hierarchical condition category (HCC) risk score, a comorbidity index calculated from a patient's comorbidities, was collected. These were stratified and compared by various physician characteristics, including practice region and rurality, years in practice, gender, subspecialty, and setting (academic vs community). RESULTS: Among 8959 ORLs, the mean HCC risk score for Medicare patients was 1.35 ± 0.35. On univariate analysis, ORLs practicing in urban (compared to rural), ORLs in academic settings (compared to community), and early career ORLs all had a patient population with a higher HCC risk score (P < .001 for all). On multivariate analysis controlling for gender, rurality, graduation year, and region, rural setting was associated with decreased odds of having a high-risk patient population (odds ratio: 0.58 [95% confidence interval, CI: 0.48-0.71]; P < .001), while those more recently graduated has an increased risk (2000-2009: 1.41 [1.01-1.96], P = .046; 2010-2015: 2.30 [1.63-3.25], P < .001). In a separate subgroup analysis, subspecialty differences were seen and community setting was associated with decreased odds of having a high-risk patient population (0.36 [0.23-0.55]; P < .001). CONCLUSION: There is variability in patient comorbidity profiles among ORLs, with those in urban settings, those more recently graduated, and those in academic settings treating a group with more comorbidities. As the comorbidity burden may increase the cost of practice and complications, these findings may have important implications for health inequity.

miR-644a is a tumor cell-intrinsic mediator of sex bias in glioblastoma.

Background: Biological sex is an important risk factor for glioblastoma (GBM), with males having a higher incidence and poorer prognosis. The mechanisms for this sex bias are thought to be both tumor intrinsic and tumor extrinsic. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have been previously linked to sex differences in various cell types and diseases, but their role in the sex bias of GBM remains unknown. Methods: We leveraged previously published paired miRNA and mRNA sequencing of 39 GBM patients (22 male, 17 female) to identify sex-biased miRNAs. We further interrogated a separate single-cell RNA sequencing dataset of 110 GBM patients to examine whether differences in miRNA target gene expression were tumor cell intrinsic or tumor cell extrinsic. Results were validated in a panel of patient-derived cell models. Results: We identified 10 sex-biased miRNAs (adjusted < 0.1), of which 3 were more highly expressed in males and 7 more highly expressed in females. Of these, miR-644a was higher in females, and increased expression of miR-644a target genes was significantly associated with decreased overall survival (HR 1.3, p = 0.02). Furthermore, analysis of an independent single-cell RNA sequencing dataset confirmed sex-specific expression of miR-644a target genes in tumor cells (p < 10-15). Among patient derived models, miR-644a was expressed a median of 4.8-fold higher in females compared to males. Conclusions: Our findings implicate miR-644a as a candidate tumor cell-intrinsic regulator of sex-biased gene expression in GBM.

Androgen loss weakens anti-tumor immunity and accelerates brain tumor growth.

Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this sex bias are unclear but likely involve differences in tumor cell state and immune response. This effect is further amplified by sex hormones, including androgens, which have been shown to inhibit anti-tumor T cell immunity. Here, we show that androgens drive anti-tumor immunity in brain tumors, in contrast to its effect in other tumor types. Upon castration, tumor growth was accelerated with attenuated T cell function in GBM and brain tumor models, but the opposite was observed when tumors were located outside the brain. Activity of the hypothalamus-pituitary-adrenal gland (HPA) axis was increased in castrated mice, particularly in those with brain tumors. Blockade of glucocorticoid receptors reversed the accelerated tumor growth in castrated mice, indicating that the effect of castration was mediated by elevated glucocorticoid signaling. Furthermore, this mechanism was not GBM specific, but brain specific, as hyperactivation of the HPA axis was observed with intracranial implantation of non-GBM tumors in the brain. Together, our findings establish that brain tumors drive distinct endocrine-mediated mechanisms in the androgen-deprived setting and highlight the importance of organ-specific effects on anti-tumor immunity.

Assessing and Improving the Effectiveness of Online Patient Education Materials on Essential Vocal Tremor: A Comprehensive Evaluation.

INTRODUCTION: Health literacy, a strong indicator of health outcomes, is an important aspect of good patient care. With an increasing reliance on the Internet for health information, online patient materials should be easily understood by the average reader. The American Medical Association (AMA) and National Institutes of Health (NIH) recommend that patient education materials be written at a sixth-grade level. Creating effective digital information requires careful consideration of not only word choice, but also many other factors including actionability, comprehensiveness, evidence, and visual organization. To support the creation of valuable online health content, the Office of Disease Prevention and Health Promotion (ODPHP) published Health Literacy Online, a research-based guide that discusses why and how to design digital health information tools.This study aims to assess the effectiveness of online patient education materials regarding vocal tremor, assess the effectiveness of patient education materials published by the American Laryngological Association, and to evaluate the usefulness of the Health Literacy Online guide in creating effective online patient education materials on laryngological diseases. METHODS: The first 50 unsponsored search results for the terms "vocal tremor" and "essential vocal tremor" were evaluated. Each website was analyzed using the Flesch Reading Ease Score (FRES) and Flesch-Kincaid Grade Level (FKGL) readability tests, the DISCERN instrument, and the Patient Education Materials Assessment Tool (PEMAT). The resources published by the American Laryngological Association were also evaluated in this manner. RESULTS: Of the 100 websites identified from the initial queries, 14 websites were included in this analysis. The average FRES and FKGL scores were 47.21 ± 10.47 and 10.96 ± 2.46, respectively, indicating that readers need a 11th-grade education to comprehend the materials. The average DISCERN score was 22.50 ± 9.76, indicating "very poor" quality with serious shortcomings and not appropriate sources of information about treatment choices. The average PEMAT understandability score was 68.43% ± 9.80% with an actionability score of 20.00% ± 23.53%, indicating the information was fairly difficult to process and do not help identify next steps. For the materials published by the American Laryngological Association (ALA), the average FRES and FKGL scores were 38.33 ± 12.81 and 12.56 ± 2.15, respectively, indicating a 12th-grade reading level. A DISCERN score of 27 was consistent across each item, indicating "very poor" quality. A PEMAT understandability score was 45% with an actionability score of 0%, indicating they are difficult to process and do not help identify next steps. After writing a revised sample of the information provided by the ALA based on the ODPHP's Health Literacy Online tool, the new FRES and FKGL score was 75.6 and 5.9, respectively. The new DISCERN score was 35. The new PEMAT understandability scores was 79% with actionability scores of 80%. CONCLUSION: This study found that most publicly available online patient education materials on essential vocal tremor and other laryngological diseases do not use plain language and require reading levels too advanced for the average reader to comprehend. In addition, most websites were of very poor quality readability, and were therefore less likely to benefit individuals in their decision-making. In an age where most people seek information on the Internet, the lack of easily understood online patient resources reduces the usefulness of these resources for many individuals. Professional organizations and societies like the American Laryngological Association may consider the use of the Health Literacy Online tool as a resource to provide both accurate and easily understandable patient education resources.

Long-range optical coherence tomography of pediatric airway during drug induced sleep endoscopy: A preliminary report.

OBJECTIVE: Drug induced sleep endoscopy (DISE) is often performed for pediatric obstructive sleep apnea (OSA) when initial diagnostic studies do not provide adequate information for therapy. However, DISE scoring is subjective and with limitations. This proof-of-concept study demonstrates the use of a novel long-range optical coherence tomography (LR-OCT) system during DISE of two pediatric patients. METHODS: LR-OCT was used to visualize the airway of pediatric patients during DISE. At the conclusion of DISE, the OCT probe was guided in the airway under endoscopic visual guidance, and cross-sectional images were acquired at the four VOTE locations. Data processing involved image resizing and alignment, followed by rendering of three-dimensional (3D) volumetric models of the airways. RESULTS: Two patients were included in this study. Patient one had 18.4%, 20.9%, 72.3%, and 97.3% maximal obstruction at velum, oropharynx, tongue base, and epiglottis, while patient two had 40.2%, 41.4%, 8.0%, and 17.5% maximal obstruction at these regions, respectively. Three-dimensional reconstructions of patients' airways were also constructed from the OCT images. CONCLUSION: This proof-of-concept study demonstrates the successful evaluation of pediatric airway during DISE using LR-OCT, which accurately identified sites and degrees of obstruction with respective 3D airway reconstruction.

Medical Student Research Activity in Otolaryngology.

OBJECTIVE: To investigate medical student research productivity by institutions associated with otolaryngology residency programs and identify correlates of productivity. STUDY DESIGN: Retrospective review. SETTING: N/A. METHODS: A systematic search for articles indexed on PubMed published by 116 programs from January 1, 2016 to February 28, 2021 was conducted. Primary outcomes were number of faculty publications, first-author medical student publications and medical students from each institution. Secondary outcomes included geographic region, number of otolaryngology faculty members, and program rankings. RESULTS: Nationally, the mean number of faculty per institution was 21.7 at the time of search. Over a 5-year period, there was a mean 98.7 total publications and 15.8 medical student first-author publications per institution consisting of a mean of 10.03 distinct medical students. One-way analysis of variance showed no statistically significant difference in medical student productivity (P = .09) or department size (P = .12) between regions. Number of medical student first-author publications positively correlated to number of faculty (R = .43, P < .05) and number of faculty publications (R = .63, P < .05). The top 30 programs ranked by United States News & World Report or National Institute of Health for funding had a statistically significantly greater mean number of medical student first-author publications and distinct medical student first authors than all other programs (P < .05). CONCLUSION: Greater numbers of faculty members likely provide more mentorship and opportunities that allow medical students to engage in projects that lead to first-author publications. These findings allow institutions to reflect on efforts in medical student engagement and provide data to students for career planning.

Severe unilateral refractory epistaxis arising from the septal branch of the anterior ethmoid artery.

KEY POINTS: The septal branch of the anterior ethmoid artery (sbAEA) is an underrecognized source of severe refractory epistaxis. Herein, we describe the presentation, predisposing factors, treatment strategies, and outcomes of a series of patients with this condition.

Homeostatic iron regulatory protein drives glioblastoma growth via tumor cell-intrinsic and sex-specific responses.

Background: Glioblastoma (GBM) displays alterations in iron that drive proliferation and tumor growth. Iron regulation is complex and involves many regulatory mechanisms, including the homeostatic iron regulator (HFE) gene, which encodes the homeostatic iron regulatory protein. While HFE is upregulated in GBM and correlates with poor survival outcomes, the function of HFE in GBM remains unclear. Methods: We interrogated the impact of cell-intrinsic Hfe expression on proliferation and survival of intracranially implanted animals through genetic gain- and loss-of-function approaches in syngeneic mouse glioma models, along with in vivo immune assessments. We also determined the expression of iron-associated genes and their relationship to survival in GBM using public data sets and used transcriptional profiling to identify differentially expressed pathways in control compared to Hfe-knockdown cells. Results: Overexpression of Hfe accelerated GBM proliferation and reduced animal survival, whereas suppression of Hfe induced apoptotic cell death and extended survival, which was more pronounced in females and associated with attenuation of natural killer cells and CD8+ T cell activity. Analysis of iron gene signatures in Hfe-knockdown cells revealed alterations in the expression of several iron-associated genes, suggesting global disruption of intracellular iron homeostasis. Further analysis of differentially expressed pathways revealed oxidative stress as the top pathway upregulated following Hfe loss. Hfe knockdown indeed resulted in enhanced 55Fe uptake and generation of reactive oxygen species. Conclusions: These findings reveal an essential function for HFE in GBM cell growth and survival, as well as a sex-specific interaction with the immune response.

Electrochemical Lipolysis Induces Adipocyte Death and Fat Necrosis: In Vivo Pilot Study in Pigs.

BACKGROUND: Current minimally invasive fat reduction modalities use equipment that can cost thousands of U.S. dollars. Electrochemical lipolysis (ECLL), using low-cost battery and electrodes (approximately $10), creates acid/base within fat (width, approximately 3 mm), damaging adipocytes. Longitudinal effects of ECLL have not been studied. In this pilot study, the authors hypothesize that in vivo ECLL induces fat necrosis, decreases adipocyte number/viability, and forms lipid droplets. METHODS: Two female Yorkshire pigs (50 to 60 kg) received ECLL. In pig 1, 10 sites received ECLL, and 10 sites were untreated. In pig 2, 12 sites received ECLL and 12 sites were untreated. For ECLL, two electrodes were inserted into dorsal subcutaneous fat and direct current was applied for 5 minutes. Adverse effects of excessive pain, bleeding, infection, and agitation were monitored. Histology, live-dead (calcein, Hoechst, ethidium homodimer-1), and morphology (Bodipy and Hoechst) assays were performed on day 0 and postprocedure days 1, 2, 7, 14 (pig 1 and pig 2), and 28 (pig 2). Average particle area, fluorescence signal areas, and adipocytes and lipid droplet numbers were compared. RESULTS: No adverse effects occurred. Live-dead assays showed adipocyte death on the anode on days 0 to 7 and the cathode on days 1 to 2 (not significant). Bodipy showed significant adipocyte loss at all sites ( P < 0.001) and lipid droplet formation at the cathode site on day 2 ( P = 0.0046). Histology revealed fat necrosis with significant increases in average particle area at the anode and cathode sites by day 14 (+277.3% change compared with untreated, P < 0.0001; +143.4%, P < 0.0001) and day 28 (+498.6%, P < 0.0001; +354.5%, P < 0.0001). CONCLUSIONS: In vivo ECLL induces fat necrosis in pigs. Further studies are needed to evaluate volumetric fat reduction. CLINICAL RELEVANCE STATEMENT: In vivo ECLL induces adipocyte death and fat necrosis. ECLL has the potential to be utilized in body fat contouring.

Temporal chromatin accessibility changes define transcriptional states essential for osteosarcoma metastasis.

The metastasis-invasion cascade describes the series of steps required for a cancer cell to successfully spread from its primary tumor and ultimately grow within a secondary organ. Despite metastasis being a dynamic, multistep process, most omics studies to date have focused on comparing primary tumors to the metastatic deposits that define end-stage disease. This static approach means we lack information about the genomic and epigenomic changes that occur during the majority of tumor progression. One particularly understudied phase of tumor progression is metastatic colonization, during which cells must adapt to the new microenvironment of the secondary organ. Through temporal profiling of chromatin accessibility and gene expression in vivo, we identify dynamic changes in the epigenome that occur as osteosarcoma tumors form and grow within the lung microenvironment. Furthermore, we show through paired in vivo and in vitro CRISPR drop-out screens and pharmacological validation that the upstream transcription factors represent a class of metastasis-specific dependency genes. While current models depict lung colonization as a discrete step within the metastatic cascade, our study shows it is a defined trajectory through multiple epigenetic states, revealing new therapeutic opportunities undetectable with standard approaches.

Tumor cell-derived spermidine promotes a pro-tumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition.

The glioblastoma microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly impact the immune system, but the mechanisms driving these interactions are not completely clear. Here we demonstrate that the polyamine metabolite spermidine is elevated in the glioblastoma tumor microenvironment. Exogenous administration of spermidine drives tumor aggressiveness in an immune-dependent manner in pre-clinical mouse models via reduction of CD8+ T cell frequency and phenotype. Knockdown of ornithine decarboxylase, the rate-limiting enzyme in spermidine synthesis, did not impact cancer cell growth in vitro but did result in extended survival. Furthermore, glioblastoma patients with a more favorable outcome had a significant reduction in spermidine compared to patients with a poor prognosis. Our results demonstrate that spermidine functions as a cancer cell-derived metabolite that drives tumor progression by reducing CD8+T cell number and function.

Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma.

Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, and emerging evidence suggests that these extend to genetic/epigenetic and cellular differences, including immune responses. However, the mechanisms driving immunologic sex differences are not fully understood. Here, we demonstrate that T cells play a critical role in driving GBM sex differences. Male mice exhibited accelerated tumor growth, with decreased frequency and increased exhaustion of CD8+ T cells in the tumor. Furthermore, a higher frequency of progenitor exhausted T cells was found in males, with improved responsiveness to anti-PD-1 treatment. Moreover, increased T-cell exhaustion was observed in male GBM patients. Bone marrow chimera and adoptive transfer models indicated that T cell-mediated tumor control was predominantly regulated in a cell-intrinsic manner, partially mediated by the X chromosome inactivation escape gene Kdm6a. These findings demonstrate that sex-biased predetermined behavior of T cells is critical for inducing sex differences in GBM progression and immunotherapy response. SIGNIFICANCE: Immunotherapies in patients with GBM have been unsuccessful due to a variety of factors, including the highly immunosuppressive tumor microenvironment in GBM. This study demonstrates that sex-biased T-cell behaviors are predominantly intrinsically regulated, further suggesting sex-specific approaches can be leveraged to potentially improve the therapeutic efficacy of immunotherapy in GBM. See related commentary by Alspach, p. 1966. This article is featured in Selected Articles from This Issue, p. 1949.

Effect of obesity on outcomes after open laryngeal surgery including total laryngectomy: A NSQIP database analysis.

BACKGROUND: The impact of obesity on outcomes after open laryngeal surgery has not been well-described. METHODS: The NSQIP database was queried for all open laryngeal surgeries including total laryngectomies between 2005 and 2018. Outcomes of patients identified as obese or nonobese by BMI were compared. RESULTS: Of 1865 patients, 20.1% classified as obese. The most common operation performed was total laryngectomy with or without radical neck dissection (73.2%). Operation time and length of hospital stay were significantly less for obese patients. On multivariate analysis, obesity was associated with less bleeding transfusions occurrences (aOR, 0.395, p = 0.0052), surgical complications (aOR, 0.604, p < 0.001), and any complication (aOR, 0.730, p = 0.0019). CONCLUSION: Though there may be an inverse association of obesity with complications and bleeding transfusion occurrences, as well as decreased operation time and length of hospital stay, several confounders and bias may exist; therefore, it is difficult to conclude that the obesity paradox is present.

Neurosarcoidosis Presenting as Longitudinally Extensive Transverse Myelitis and Orbital Mass: A Case Report.

We describe a case of neurosarcoidosis in a 64-year-old female who presented with proptosis and orbital inflammation together with bilateral lower extremity neuropathy and longitudinally extensive transverse myelitis. These two entities are not commonly associated, and the etiology of the transverse myelitis was facilitated by an orbital biopsy. The transverse myelitis caused numbness in her lower extremities and tightness in her chest and abdomen, which progressed over weeks to difficulty walking and bilateral neuromuscular weakness. Magnetic resonance imaging (MRI) revealed longitudinally extensive transverse myelitis in the cervical and thoracic spine. Computed tomography (CT) imaging of the chest revealed right hilar and mediastinal lymphadenopathy and calcified subcarinal nodes. Positron emission tomography (PET) scan revealed hypermetabolism in the mediastinum and medial left orbit. Orbital biopsy revealed non-necrotizing granulomatous inflammation suggestive of sarcoidosis. The neurologic deficits and orbital inflammation responded well to intravenous corticosteroids. Neurosarcoidosis can present with unusual clinical manifestations, as evidenced by this patient.

Diagnosis and Management of Barosinusitis: A Systematic Review.

OBJECTIVE: To perform a systematic review to investigate the common presenting symptoms of barosinusitis, the incidence of those findings, the methods for diagnosis, as well as the medical and surgical treatment options. METHODS: A review of PubMed/MEDLINE, EMBASE, and Cochrane Library for articles published between 1967 and 2020 was conducted with the following search term: aerosinusitis OR "sinus squeeze" OR barosinusitis OR (barotrauma AND sinusitis) OR (barotrauma AND rhinosinusitis). Twenty-seven articles encompassing 232 patients met inclusion criteria and were queried for demographics, etiology, presentation, and medical and surgical treatments. RESULTS: Mean age of patients was 33.3 years, where 21.7% were females and 78.3% were males. Causes of barotrauma include diving (57.3%), airplane descent (26.7%), and general anesthesia (0.4%). The most common presentations were frontal pain (44.0%), epistaxis (25.4%), and maxillary pain (10.3%). Most patients received topical steroids (44.0%), oral steroids (28.4%), decongestants (20.7%), and antibiotics (15.5%). For surgical treatment, most patients received functional endoscopic sinus surgery (FESS) (49.6%). Adjunctive surgeries include middle meatal or maxillary antrostomy (20.7%), septoplasty (15.5%), and turbinate surgery (9.1%). The most efficacious medical treatments are as follows: 63.6% success rate with oral steroids (66 treated), 50.0% success rate with topical steroids (102 treated), and 50.0% success rate analgesics (10 treated). For surgical treatments received by greater than 10% of the sample, the most efficacious was FESS (91.5% success rate, 108 treated). CONCLUSION: Oral and topical steroids should be first line therapies. If refractory, then functional endoscopic sinus surgery is an effective treatment.

In vivo electrochemical lipolysis of fat in a Yucatan pig model: A proof of concept study.

OBJECTIVES: Traditional fat contouring is now regularly performed using numerous office- based less invasive techniques. However, some limitations of these minimally invasive techniques include high cost or limited selectivity with performing localized contouring and reduction of fat. These shortcomings may potentially be addressed by electrochemical lipolysis (ECLL), a novel approach that involves the insertion of electrodes into tissue followed by application of a direct current (DC) electrical potential. This results in the hydrolysis of tissue water creating active species that lead to fat necrosis and apoptosis. ECLL can be accomplished using a simple voltage-driven system (V-ECLL) or a potential-driven feedback cell (P-ECLL) both leading to water electrolysis and the creation of acid and base in situ. The aim of this study is to determine the long-lasting effects of targeted ECLL in a Yucatan pig model. METHODS: A 5-year-old Yucatan pig was treated with both V-ECLL and P-ECLL in the subcutaneous fat layer using 80:20 platinum:iridium needle electrodes along an 8 cm length. Dosimetry parameters included 5 V V-ECLL for 5, 10, and 20 minutes, and -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL for 5 minutes. The pig was assessed for changes in fat reduction over 3 months with digital photography and ultrasound. After euthanasia, tissue sections were harvested and gross pathology and histology were examined. RESULTS: V-ECLL and P-ECLL treatments led to visible fat reduction (12.1%-27.7% and 9.4%-40.8%, respectively) and contour changes across several parameters. An increased reduction of the superficial fat layer occurred with increased dosimetry parameters with an average charge transfer of 12.5, 24.3, and 47.5 C transferred for 5 V V-ECLL for 5, 10, and 20 minutes, respectively, and 2.0, 11.5, and 24.0 C for -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL for 5 minutes, respectively. These dose-dependent changes were also evidenced by digital photography, gross pathology, ultrasound imaging, and histology. CONCLUSIONS: ECLL results in selective damage and long-lasting changes to the adipose layer in vivo. These changes are dose-dependent, thus allowing for more precise contouring of target areas. P-ECLL has greater efficiency and control of total charge transfer compared to V-ECLL, suggesting that a low-voltage potentiostat treatment can result in fat apoptosis equivalent to a high-voltage DC system.

Mitochondrial Autoantibodies and the Role of Apoptosis in Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is an IgG autoantibody-mediated, potentially fatal mucocutaneous disease manifested by progressive non-healing erosions and blisters. Beyond acting to inhibit adhesion molecules, PVIgGs elicit a unique process of programmed cell death and detachment of epidermal keratinocytes termed apoptolysis. Mitochondrial damage by antimitochondrial antibodies (AMA) has proven to be a critical link in this process. AMA act synergistically with other autoantibodies in the pathogenesis of PV. Importantly, absorption of AMA inhibits the ability of PVIgGs to induce blisters. Pharmacologic agents that protect mitochondrial function offer a new targeted approach to treating this severe immunoblistering disease.

Visualization of ex vivo rabbit olfactory mucosa and foramina with three-dimensional optical coherence tomography.

There is increasing interest in developing a minimally invasive imaging modality to safely evaluate dynamic microscopic changes of the olfactory mucosa and cribriform foramina. Herein, we utilized three-dimensional (3D) optical coherence tomography (OCT) to characterize the ex vivo stratified substructure of olfactory mucosa in rabbits and create 3D reconstructed images of olfactory foramina. Olfactory mucosa and cribriform plates from four New Zealand White rabbits were dissected and imaged using two swept-source OCT systems: (1) 1.3-µm (µm) center wavelength, 100-nm bandwidth, 200-kHz sweep rate, and (2) 1.7-µm center wavelength, 120-nm bandwidth, 90-kHz sweep rate. Volumetric OCT images were compiled to create a 3D reconstruction of the cribriform plate. The ability of OCT to distinguish the olfactory mucosa substructure and foramina was compared to histology. To estimate imaging penetration depth of each system, the first-order exponential decays of depth-resolved intensity were calculated and compared using a paired t-test. Three-dimensional OCT depicted the stratified layered structures within the olfactory mucosa correlating with histology. The epithelium and lamina propria were measured to be 32 µm and 107 µm in 1.3-µm OCT compared to 30 µm and 105 µm in histology. Olfactory foramina were visualized via 3D reconstruction. The 1.7-µm system provided greater depth penetration compared to the 1.3-µm system, allowing for improved foramina visualization. We have shown that OCT can be used to image non-pathologic olfactory mucosa and foramina. Implications for this work include diagnostic and therapeutic potentials for neurorhinological and neurodegenerative diseases.