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Δευτέρα 16 Αυγούστου 2021

Exercise-Induced Hypoalgesia Profile in a Rat Neuropathic Pain Model Predicts Pain Severity Following Infraorbital Nerve Injury and Is Associated with Local Cytokine Levels, Systemic Endocannabinoids, and Endogenous Opioids

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J Oral Facial Pain Headache. 2021 Aug 16. doi: 10.11607/ofph.3003. Online ahead of print.

ABSTRACT

AIMS: To investigate the role of exercise-induced hypoalgesia (EIH) in the development of neuropathic pain (NP) following infraorbital nerve (ION) injury and to explore possible underlying mechanisms defining the differences between rats with high and low EIH.

METHODS: EIH was evaluated by measuring the percentage of withdrawal responses to a series of 30 mechanical stimu li applied to the hind paw before and after 180 seconds of exercise on a rotating rod. The rats were assigned to low- and high-EIH groups based on reduction in the percent of withdrawal responses following exercise. NP was induced in high- and low-EIH rats via ION constriction injury. Rats were tested with graded nylon monofilaments to establish the withdrawal threshold. Increasingly stiff monofilaments were applied to the ION territory until there was a clear withdrawal by the rat. This was repeated a total of three times. A decreased withdrawal threshold indicates allodynia. Testing was performed at baseline and at 3, 10, and 17 days following the injury. On day 17 postinjury, IONs were harvested for the assessment of interleukin (IL)-6, IL-1β, and IL-10 levels. Samples from high-EIH and low-EIH surgically naïve rats served as control for the cytokines study. In this second part of the study, the effects of cannabinoid 1 (CB1) and cannabinoid 2 (CB2) antagonists and naltrexone o n EIH profiles and on the withdrawal thresholds to mechanical stimulation were measured. EIH and withdrawal thresholds in high- and low-EIH rats were measured before and after administration of antagonists.

RESULTS: Low-EIH rats developed significantly more pronounced allodynia in the ION territory following injury compared to high-EIH rats. At 17 days postinjury, ION IL-1β levels were higher in low-EIH rats, and IL-10 levels were higher in high-EIH rats. CB1 antagonist blocked the analgesic effect induced by exercise in high- but not in low-EIH rats. The CB2 antagonist had no significant effect on high- or low-EIH rats. Naltrexone blocked the effects of EIH in both high- and low-EIH rats. Exercise induced a significant analgesic effect in high-EIH but not in low-EIH rats. CB1 or CB2 antagonist administration had no effect on pre-exercise responses to mechanical stimulation, while naltrexone administration resulted in significant allodynia in both low- and high-EIH rats.

< p>CONCLUSION: This study demonstrated substantial differences between rats with high and low EIH. The results suggest that following ION injury, high-EIH rats may have a more prominent or activated endocannabinoids system and that their inflammatory response is moderated, with higher levels of IL-10 and lower levels of IL-1β.

PMID:34398938 | DOI:10.11607/ofph.3003

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Is Fas‐mediated apoptosis of melanocytes indispensable in vitiligo?

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Abstract

With interest, we have read the article by Jimbo et al. in Experimental Dermatology 1. The authors reported that the Fas pathway is involved in CD8+ T-lymphocyte-dependent depigmentation in a vitiligo mouse model. Tumor necrosis factor (TNF)-α and interferon, (IFN)-γ whose expression is elevated in lesional skin of vitiligo patients, synergistically upregulated Fas expression but suppressed Fas-mediated apoptosis of human melanocytes in vitro. While there is no doubt that vitiligo results in cell death of these cells we wondered if patients with mutations of the FAS gene are resistant to develop vitiligo.

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Κυριακή 15 Αυγούστου 2021

Outcomes between intensity‐modulated radiation therapy versus 3D‐conformal in early stage glottic cancer

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Abstract

Background

The purpose of this study is to evaluate practice patterns and outcomes between intensity-modulated radiation therapy (IMRT) and 3D-conformal radiation (3D-CRT) in early stage glottic cancer.

Methods

The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify and compare patient and disease profiles, mortality, and toxicity in patients with T1-2 larynx cancer undergoing definitive radiation (RT).

Results

A total of 1520 patients underwent definitive radiation with 3D-CRT (n = 1309) or IMRT (n = 211). Non-white race, those with a Charlson Comorbidity Index ≥2, T2 disease, and those treated at community practices were more likely to undergo IMRT. Rates of IMRT increased from 2006 to 2015, while relative rates of 3D-CRT decreased. Two-year CSS was superior with 3D-CRT (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.22–0.65; p < 0.001). There was no difference in OS between 3D-CRT and IMRT (p = 0.119).

Conclusions

Patients receiving 3D-CRT had improved CSS compared to IMRT with no difference in OS.

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Transoral endoscopic thyroidectomy vestibular approach: Experience from a multicenter national group with 412 patients

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Abstract

Background

Well-established conventional thyroidectomy has satisfactory outcomes; however, robotic and endoscopic thyroid surgery can avoid visible anterior neck scars. Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is the most recent of these techniques.

Methods

This was a retrospective review of 412 patients who underwent TOETVA from 2017 to 2020 in 13 Brazilian centers.

Results

The study included 359 (87.1%) females and 53 (12.9%) males, with a mean age of 40 years. There were 231 (56.1%) total thyroidectomies. The conversion rate was 0.7%. The transient vocal cord palsy rate was 7.6% (30 patients). Temporary and persistent hypocalcemia rates were 4.0% and 0.8%, respectively. There were two cases of infection (0.5%).

Discussion

This is a large multi-institute TOETVA study, with one of the largest cohorts published to date that; despite its retrospective nature and selection bias, reached outcomes comparable to previously reported series, this study reinforced safeness, feasibility, and nationwide reproducibility for this technique.

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Evaluation of Sarcopenia in Older Patients Undergoing Head and Neck Cancer Surgery

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Objectives/Hypothesis

Sarcopenia is a hallmark of aging and its identification may help predict adverse postoperative events in patients undergoing head and neck surgery. The study objective was to assess the relationship between sarcopenia and postoperative complications and length of stay in patients undergoing major head and neck cancer surgery.

Study Design

Prospective cohort study.

Methods

A prospective cohort study was performed of patients 50 years and older undergoing major head and neck surgery. Sarcopenia was defined as low muscle mass (determined by neck muscle cross-sectional imaging) with either low muscle strength (grip strength) or low muscle performance (timed walk test). Logistic regression was applied on binary outcomes, and linear regression was used for log-transformed length of hospital stay (LOS). Univariate and multivariate analyses were performed.

Results

Of the 251 patients enrolled, pre-sarcopenia was present in 34.9% (n = 87) and sarcopenia in 15.6% (n = 39) of patients. Patients with sarcopenia were more likely to be older (P = .001), female (P = .001), have a lower body mass index (P = .001), and lower preoperative hemoglobin (P < .001). On univariate analysis, the presence and severity of sarcopenia was associated with the development of medical complications (P = .029), higher grade of complications (P = .032), LOS (P = .015), and overall survival (P = .001). On multivariate analysis, sarcopenia was associated with a longer LOS (β = 0.32 [95% CI: 0.19–0.45], P < .001) and worse overall survival (HR = 2.21 [95% CI: 1.01–4.23], P = .017).

Conclusions

Sarcopenia may aid in the prediction of prolonged hospital stay and death in patients who are candidates for major head and neck surgery.

Level of Evidence

3 Laryngoscope, 2021

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Assessing Human Papillomavirus Awareness and the Role of Oropharyngeal Squamous Cell Carcinoma Education on Improving Intention to Vaccinate

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Objectives/Hypothesis

The current state of the U.S. public's knowledge of the relationship between human papillomavirus (HPV) and HPV vaccinations to oropharyngeal squamous cell carcinoma (OPSCC) is unknown. Our objective was to 1) assess the general population's knowledge of human papillomavirus (HPV) and willingness to vaccinate, and 2) assess whether targeted education on HPV-related OPSCC can change intentions to vaccinate.

Study Design

Online cross-sectional survey.

Methods

An online, cross-sectional survey utilizing U.S. census-derived quotas to represent the U.S. population was distributed and analyzed to 517 adults in 2020.

Results

Exactly 72.7% of participants stated that they had or would vaccinate their child against HPV and were designated as "vaccinators." In multivariate regression, Black individuals were less likely to be vaccinators (OR 0.51 [95% CI 0.27–0.94]), but those who were aware of HPV's role in OPSCC were more likely to vaccinate (OR 2.56 [95% CI 1.47–4.46]). Knowledge about vaccination side-effects, eligibility, and mechanisms of HPV spread was low. Only 30.6% of the sample reported understanding the role of HPV in OPSCC. Of these, 43.0% gained this knowledge exclusively from nonhealthcare professional sources, like television. When presented with four short HPV-OPSCC-centered facts (HPV's role in OPSCC etiology, prevalence of infection, clinically silent course, and vaccine preventative effects), 54.0% of "nonvaccinators" indicated a willingness to change their minds.

Conclusions

General knowledge about HPV, HPV's role in OPSCC, and the vaccine remains low in the general population. There are racial disparities in willingness to vaccinate within this sample, but these may be overcome by effective education on HPV-related OPSCC.

Level of Evidence

3 Laryngoscope, 2021

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Magnetic Resonance Imaging Findings Among Individuals With Olfactory and Cognitive Impairment

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Objectives

The underlying mechanism of the association between olfactory impairment and dementia may be explained by neurodegenerative changes detected on magnetic resonance imaging (MRI). The purpose of this systematic review is to describe neurodegenerative changes on MRI in patients with olfactory impairment and mild cognitive impairment (MCI) or dementia.

Study design

Systematic review.

Methods

A literature search encompassing PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Google Scholar for studies with MRI and olfactory testing among participants diagnosed with MCI or dementia was performed. Sample size, study design, cognitive impairment type, olfactory testing, and MRI findings were abstracted. Two investigators independently reviewed all articles.

Results

The search yielded 556 nonduplicate abstracts, from which 86 articles were reviewed and 24 were included. Seventeen (71%) of 24 studies reported hippocampal volume findings, with 14 studies reporting a relationship between hippocampal volume and olfactory performance. Two (50%) of four prospective studies reported the potential utility of baseline hippocampal volume as a marker of dementia conversion from MCI. Five (21%) of 24 studies reporting olfactory functional MRI (fMRI) findings highlighted the utility of olfactory fMRI to identify individuals in the early stages of cognitive decline.

Conclusion

Current evidence suggests hippocampal volume correlates with olfactory performance in individuals with cognitive impairment, and that olfactory fMRI may improve early detection of AD. However, the predictive utility of these imaging markers is limited in prospective studies. MRI may be a useful modality for selecting patients at high risk of future cognitive decline for enrollment in early treatment trials. Laryngoscope, 2021

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Cell Type–Specific Expression Analysis of the Inner Ear: A Technical Report

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Objective

The cellular diversity of the inner ear has presented a technical challenge in obtaining molecular insight into its development and function. The application of technological advancements in cell type–specific expression enable clinicians and researchers to leap forward from classic genetics to obtaining mechanistic understanding of congenital and acquired hearing loss. This understanding is essential for development of therapeutics to prevent and reverse diseases of the inner ear, including hearing loss. The objective of this study is to describe and compare the available tools for cell type–specific analysis of the ear, as a means to support decision making in study design.

Study Design

Three major approaches for cell type–specific analysis of the ear including fluorescence-activated cell sorting (FACS), ribosomal and RNA pulldown techniques, and single cell RNA-seq (scRNA-seq) are compared and contrasted using both published and original data.

Results

We demonstrate the strength and weaknesses of these approaches leading to the inevitable conclusion that to maximize the utility of these approaches, it is important to match the experimental approach with the tissue of origin, cell type of interest, and the biological question. Often, a combined approach (eg, cell sorting and scRNA-seq or expression analysis using 2 separate approaches) is required. Finally, new tools for visualization and analysis of complex expression data, such as the gEAR platform (umgear.org), collate cell type–specific gene expression from the ear field and provide unprecedented access to both clinicians and researchers.

Level of Evidence

N/A Laryngoscope, 131:S1–S16, 2021

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Development of a Bioinspired, Self‐Adhering, and Drug‐Eluting Laryngotracheal Patch

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Objectives/Hypothesis

Novel laryngotracheal wound coverage devices are limited by complex anatomy, smooth surfaces, and dynamic pressure changes and airflow during breathing. We hypothesize that a bioinspired mucoadhesive patch mimicking how geckos climb smooth surfaces will permit sutureless wound coverage and also allow drug delivery.

Study Design

ex-vivo.

Methods

Polycaprolactone (PCL) fibers were electrospun onto a substrate and polyethylene glycol (PEG) – acrylate flocks in varying densities were deposited to create a composite patch. Sample topography was assessed with laser profilometry, material stiffness with biaxial mechanical testing, and mucoadhesive testing determined cohesive material failure on porcine tracheal tissue. Degradation rate was measured over 21 days in vitro along with dexamethasone drug release profiles. Material handleability was evaluated via suture retention and in cadaveric larynges.

Results

Increased flocking density was inversely related to cohesive failure in mucoadhesive testing, with a flocking density of PCL-PEG-2XFLK increasing failure strength to 6880 ± 1810 Pa compared to 3028 ± 791 in PCL-PEG-4XFLK density and 1182 ± 262 in PCL-PEG-6XFLK density. The PCL-PEG-2XFLK specimens had a higher failure strength than PCL alone (1404 ± 545 Pa) or PCL-PEG (2732 ± 840). Flocking progressively reduced composite stiffness from 1347 ± 15 to 763 ± 21 N/m. Degradation increased from 12% at 7 days to 16% after 10 days and 20% after 21 days. Cumulative dexamethasone release at 0.4 mg/cm2 concentration was maintained over 21 days. Optimized PCL-PEG-2XFLK density flocked patches were easy to maneuver endoscopically in laryngeal evaluation.

Conclusions

This novel, sutureless, patch is a mucoadhesive platform suitable to laryngeal and tracheal anatomy with drug delivery capability.

Level of Evidence

NA Laryngoscope, 131:1958–1966, 2021

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Office‐Based Procedure Training in Laryngology Fellowship Programs

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Objective

To assess the current practices and challenges of training office-based procedures to laryngology fellows in the United States.

Methods

An anonymous web-based survey study was distributed to laryngology fellowship program directors, as listed by the American Laryngological Association. The survey was a 19-item questionnaire with free-text, Likert scale, and multiple-choice answers.

Results

Twenty-two of 27 program directors (81.4%) replied to the survey. Many programs (8/16) have three or more laryngologists and do more than 10 procedures each week (10/16). Sixty-nine percent (11/16) of directors had not been trained for office procedures in their fellowship. The fellows are allowed to be primary surgeon on 68.75% and 75% of vocal fold augmentation and laser procedures, respectively. The expected competencies for these procedures on graduation are average-moderate and moderate. When program directors asked about the methods used for training, a minority of them use simulators (2/16), procedural checklists (2/16), or structured debriefing (2/16). The most commonly used methods were case-based troubleshooting (13/16) and unstructured debriefing (13/16). Patients being awake and patients' expectations are seen as the most important obstacles. Most of the directors thought office-based procedure training could be improved (14/16). The most common suggestions were using step-wise checklists, simulator-labs, and formal debriefings.

Conclusion

This is the first study evaluating the training of office-based laryngeal procedures during laryngology fellowship. Given the increasing importance of these procedures in practice and the herein identified barriers and need for improvement, fellowships should investigate the use of systematic training tools to improve fellow competency with office-based procedures. Laryngoscope, 131:2054–2058, 2021

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Laryngeal Pathologies Associated with the Genre of Singing and Professional Singing Status in a Treatment‐Seeking Population

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Objectives/Hypothesis

Singers have high vocal demands and are at increased risk of developing voice disorders. Different singing genres place different technical demands on the voice. However, differences in laryngeal pathology based on genre have not been well-researched. The purpose of this study was to determine the prevalence of laryngeal pathology in different genres of professional and amateur singers who present with a voice complaint.

Study Design

Retrospective review.

Methods

Retrospective review of patients seen at a tertiary laryngology practice. Self-identified singers who reported their primary singing genre and categorized their singing as a full-time job, part-time job, or amateur involvement were included. Type and prevalence of pathology were calculated based on genre and professional status.

Results

Of the 302 self-identified singers, 54% (n = 164) had laryngeal pathology. Among those with pathology, the most common finding was fibrotic lesion (38.4%, 63/164). Genres in which a majority of singers had pathology were other (69.2%, 9/13), choral (64.7%, 11/17), pop (63.2%, 12/19), musical theater (61.4%, 43/70), country (100%, 4/4), and Latin (100%, 2/2). The highest prevalence of pathology was seen in part-time professional singers (62.2%, 41/66) and full-time professionals (60.8%, 62/102), compared to amateurs (45.1%, 60/133).

Conclusions

Laryngeal pathology is prevalent in singers presenting with a voice complaint. Regardless of genre or professional status, fibrotic lesions were the most common pathological finding. This study provides preliminary data on the prevalence of different laryngeal pathologies found in singers by genre and degree of professional involvement.

Level of Evidence

4 Laryngoscope, 131:2076–2080, 2021

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