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The correlation between codon and anticodon pools influences the efficiency of translation, but whether differences exist in these pools across individual cells is unknown. We determined that codon usage and amino acid demand are highly stable across different cell types using available mouse and human single-cell RNA-sequencing atlases. After showing the robustness of ATAC-sequencing measurements for the analysis of tRNA gene usage, we quantified anticodon usage and amino acid supply in both mouse and human single-cell ATAC-seq atlases. We found that tRNA gene usage is overall coordinated across cell types, except in neurons, which clustered separately from other cell types. Integration of these data sets revealed a strong and statistically significant correlation between amino acid supply and demand across almost all cell types. Neurons have an enhanced translation efficiency over other cell types, driven by an increased supply of tRNAAla (AGC) anticodons. This results in faster decoding of the Ala-GCC codon, as determined by cell type-specific ribosome profiling, suggesting that the reduction of tRNAAla (AGC) anticodon pools may be implicated in neurological pathologies. This study, the first such examination of codon usage, anticodon usage, and translation efficiency resolved at the cell-type level with single-cell information, identifies a conserved landscape of translation elongation across mammalian cellular diversity and evolution.
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Anticódon , RNA de Transferência , Animais , Anticódon/genética , Códon , Camundongos , Neurônios/metabolismo , Biossíntese de Proteínas , RNA Mensageiro/genética , RNA de Transferência/genética , RNA de Transferência/metabolismoRESUMO
Covariation induced by compensatory base substitutions in RNA alignments is a great way to deduce conserved RNA structure, in principle. In practice, success depends on many factors, importantly the quality and depth of the alignment and the choice of covariation statistic. Measuring covariation between pairs of aligned positions is easy. However, using covariation to infer evolutionarily conserved RNA structure is complicated by other extraneous sources of covariation such as that resulting from homologous sequences having evolved from a common ancestor. In order to provide evidence of evolutionarily conserved RNA structure, a method to distinguish covariation due to sources other than RNA structure is necessary. Moreover, there are several sorts of artifactually generated covariation signals that can further confound the analysis. Additionally, some covariation signal is difficult to detect due to incomplete comparative data. Here, we investigate and critically discuss the practice of inferring conserved RNA structure by comparative sequence analysis. We provide new methods on how to approach and decide which of the numerous long non-coding RNAs (lncRNAs) have biologically relevant structures.
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RNA Longo não Codificante , Conformação de Ácido Nucleico , Alinhamento de SequênciaRESUMO
Many non-coding RNAs with known functions are structurally conserved: their intramolecular secondary and tertiary interactions are maintained across evolutionary time. Consequently, the presence of conserved structure in multiple sequence alignments can be used to identify candidate functional non-coding RNAs. Here, we present a bioinformatics method that couples iterative homology search with covariation analysis to assess whether a genomic region has evidence of conserved RNA structure. We used this method to examine all unannotated regions of five well-studied fungal genomes (Saccharomyces cerevisiae, Candida albicans, Neurospora crassa, Aspergillus fumigatus, and Schizosaccharomyces pombe). We identified 17 novel structurally conserved non-coding RNA candidates, which include four H/ACA box small nucleolar RNAs, four intergenic RNAs and nine RNA structures located within the introns and untranslated regions (UTRs) of mRNAs. For the two structures in the 3' UTRs of the metabolic genes GLY1 and MET13, we performed experiments that provide evidence against them being eukaryotic riboswitches.
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RNA Fúngico/química , RNA não Traduzido/química , Regiões 3' não Traduzidas , Biologia Computacional/métodos , Genoma Fúngico , Íntrons , Lisina-tRNA Ligase/genética , Cadeias de Markov , Conformação de Ácido Nucleico , RNA Nucleolar Pequeno/química , Proteínas Ribossômicas/genética , Riboswitch , Alinhamento de Sequência , Tiorredoxinas/genéticaRESUMO
The morphogenesis of vaccinia virus (VACV, family Poxviridae), the smallpox vaccine, is a complex process involving multiple distinct cellular membranes and resulting in multiple different forms of infectious virion. Efficient release of enveloped virions, which promote systemic spread of infection within hosts, requires the VACV protein E2 but the molecular basis of E2 function remains unclear and E2 lacks sequence homology to any well-characterised family of proteins. We solved the crystal structure of VACV E2 to 2.3 Å resolution, revealing that it comprises two domains with novel folds: an N-terminal annular (ring) domain and a C-terminal globular (head) domain. The C-terminal head domain displays weak structural homology with cellular (pseudo)kinases but lacks conserved surface residues or kinase features, suggesting that it is not enzymatically active, and possesses a large surface basic patch that might interact with phosphoinositide lipid headgroups. Recent deep learning methods have revolutionised our ability to predict the three-dimensional structures of proteins from primary sequence alone. VACV E2 is an exemplar 'difficult' viral protein target for structure prediction, being comprised of multiple novel domains and lacking sequence homologues outside Poxviridae. AlphaFold2 nonetheless succeeds in predicting the structures of the head and ring domains with high and moderate accuracy, respectively, allowing accurate inference of multiple structural properties. The advent of highly accurate virus structure prediction marks a step-change in structural virology and beckons a new era of structurally-informed molecular virology.
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Poxviridae/metabolismo , Vaccinia virus/química , Vaccinia virus/fisiologia , Proteínas Virais/química , Proteínas Virais/metabolismo , Replicação Viral , Sítios de Ligação , Cristalografia por Raios X , Ligação Proteica , Conformação Proteica , Vaccinia virus/genética , Proteínas Virais/genéticaRESUMO
Vaccinia virus (VACV) utilizes microtubule-mediated trafficking at several stages of its life cycle, of which virus egress is the most intensely studied. During egress VACV proteins A36, F12 and E2 are involved in kinesin-1 interactions; however, the roles of these proteins remain poorly understood. A36 forms a direct link between virions and kinesin-1, yet in its absence VACV egress still occurs on microtubules. During a co-immunoprecipitation screen to seek an alternative link between virions and kinesin, A36 was found to bind isoform KLC1 rather than KLC2. The F12/E2 complex associates preferentially with the C-terminal tail of KLC2, to a region that overlaps the binding site of cellular 14-3-3 proteins. F12/E2 displaces 14-3-3 from KLC and, unlike 14-3-3, does not require phosphorylation of KLC for its binding. The region determining the KLC1 specificity of A36 was mapped to the KLC N-terminal heptad repeat region that is responsible for its association with kinesin heavy chain. Despite these differing binding properties F12/E2 can co-operatively enhance A36 association with KLC, particularly when using a KLC1-KLC2 chimaera that resembles several KLC1 spliceforms and can bind A36 and F12/E2 efficiently. This is the first example of a pathogen encoding multiple proteins that co-operatively associate with kinesin-1.
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Cinesinas/metabolismo , Isoformas de Proteínas/metabolismo , Vaccinia virus/metabolismo , Proteínas Virais/metabolismo , Proteínas 14-3-3/metabolismo , Animais , Linhagem Celular , Humanos , Ligação Proteica , Transporte ProteicoRESUMO
Implantation of acellular biomimetic scaffolds with proangiogenic motifs may have exciting clinical utility for the treatment of ischemic pathologies such as myocardial infarction. Although direct delivery of angiogenic proteins is a possible treatment option, smaller synthetic peptide-based nanostructured alternatives are being investigated due to favorable factors, such as sustained efficacy and high-density epitope presentation of functional moieties. These peptides may be implanted in vivo at the site of ischemia, bypassing the first-pass metabolism and enabling long-term retention and sustained efficacy. Mimics of angiogenic proteins show tremendous potential for clinical use. We discuss possible approaches to integrate the functionality of such angiogenic peptide mimics into self-assembled peptide scaffolds for application in functional tissue regeneration.
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Neovascularização Fisiológica , Peptídeos/química , Regeneração , Alicerces Teciduais/química , Indutores da Angiogênese/química , Indutores da Angiogênese/farmacologia , Animais , HumanosRESUMO
During vaccinia virus morphogenesis, intracellular mature virus (IMV) particles are wrapped by a double lipid bilayer to form triple enveloped virions called intracellular enveloped virus (IEV). IEV are then transported to the cell surface where the outer IEV membrane fuses with the cell membrane to expose a double enveloped virion outside the cell. The F12, E2 and A36 proteins are involved in transport of IEVs to the cell surface. Deletion of the F12L or E2L genes causes a severe inhibition of IEV transport and a tiny plaque size. Deletion of the A36R gene leads to a smaller reduction in plaque size and less severe inhibition of IEV egress. The A36 protein is present in the outer membrane of IEVs, and over-expressed fragments of this protein interact with kinesin light chain (KLC). However, no interaction of F12 or E2 with the kinesin complex has been reported hitherto. Here the F12/E2 complex is shown to associate with kinesin-1 through an interaction of E2 with the C-terminal tail of KLC isoform 2, which varies considerably between different KLC isoforms. siRNA-mediated knockdown of KLC isoform 1 increased IEV transport to the cell surface and virus plaque size, suggesting interaction with KLC isoform 1 is somehow inhibitory of IEV transport. In contrast, knockdown of KLC isoform 2 did not affect IEV egress or plaque formation, indicating redundancy in virion egress pathways. Lastly, the enhancement of plaque size resulting from loss of KLC isoform 1 was abrogated by removal of KLC isoforms 1 and 2 simultaneously. These observations suggest redundancy in the mechanisms used for IEV egress, with involvement of KLC isoforms 1 and 2, and provide evidence of interaction of F12/E2 complex with the kinesin-1 complex.
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Proteínas Associadas aos Microtúbulos/metabolismo , Vaccinia virus/metabolismo , Vaccinia virus/patogenicidade , Proteínas Virais/metabolismo , Citometria de Fluxo , Células HeLa , Humanos , Immunoblotting , Imunoprecipitação , Cinesinas , Microscopia Confocal , Transporte Proteico/fisiologia , TransfecçãoRESUMO
During aerial exposure (emersion), most sessile intertidal invertebrates experience cellular stress caused by hypoxia, and the amount and types of hypoxia-induced stress will differ as exposure time increases, likely leading to altered metabolic responses. We examined proteomic responses to increasing emersion times and decreasing recovery (immersion) times in the mussel Geukensia demissa, which occurs in salt marshes along the east coast of North America. Individuals are found above mean tide level, and can be emersed for over 18 h during spring tides. We acclimated mussels to full immersion at 15°C for 4 weeks, and compared changes in gill protein expression between groups of mussels that were continually immersed (control), were emersed for 6 h and immersed during recovery for 18 h (6E/18R), were emersed for 12 h and recovered for 12 h (12E/12R), or were emersed for 18 h with a 6 h recovery (18E/6R). We found clear differences in protein expression patterns among the treatments. Proteins associated with anaerobic fermentation increased in abundance in 6E/18R but not in 12E/12R or 18E/6R. Increases in oxidative stress proteins were most apparent in 12E/12R, and in 18E/6R changes in cytoskeletal protein expression predominated. We conclude that G. demissa alters its strategy for coping with emersion stress over time, relying on anaerobic metabolism for short- to medium-duration exposure, but switching to an air-gaping strategy for long-term exposure, which reduces hypoxia stress but may cause structural damage to gill tissue.
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Bivalves/metabolismo , Brânquias/metabolismo , Hipóxia , Proteoma/metabolismo , Estresse Fisiológico , Aerobiose , Anaerobiose , Animais , Bivalves/fisiologia , Imersão , Proteínas/metabolismo , Ondas de MaréRESUMO
OBJECTIVE: Vocal fold scar and sulcus pose significant treatment challenges with no current optimal treatment. Platelet-rich plasma (PRP), an autologous concentration of growth factors, holds promise for regenerating the superficial lamina propria. This study aims to evaluate the potential benefits of serial PRP injections on mucosal wave restoration and vocal function. METHODS: In a prospective clinical trial across two institutions, patients with vocal fold scar underwent four serial PRP injections, one month apart. Blinded independent laryngologists and expert listeners used pretreatment and one-month post-fourth injection videostroboscopy and CAPE-V assessments to evaluate mucosal wave and voice quality changes, respectively. Additionally, patient reported outcome measures (PROMs) were evaluated. RESULTS: In the study, 15 patients received 55 PRP injections without adverse effects. Eight patients (53.3%) had mild, three patients (20%) had moderate, and four patients (26.7%) had severe scar. There was an average reduction of 8.7 points in post-treatment VHI-10 scores (p = 0.007). The raters observed an improvement in post-treatment voice in 73.4% of cases, and CAPE-V scores showed a reduction of 18.8 points on average (p = 0.036). The videostroboscopic VALI ratings showed an improvement in mucosal wave rating from 2.0 to 4.0. On average, the raters perceived the post-PRP exams to be better in 56.7% of cases. CONCLUSIONS: PRP has been validated as a safe autologous option for treatment of vocal fold scar. While results for mucosal wave and voice quality varied, there was a consistent improvement in PROMs. LEVEL OF EVIDENCE: Level 3: Prospective cohort study, with blinded analysis Laryngoscope, 2024.
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Breast cancer is one of the leading causes of cancer mortality. Breast cancer patients in developing countries, especially sub-Saharan Africa, South Asia, and South America, suffer from the highest mortality rate in the world. One crucial factor contributing to the global disparity in mortality rate is long delay of diagnosis due to a severe shortage of trained pathologists, which consequently has led to a large proportion of late-stage presentation at diagnosis. To tackle this critical healthcare disparity, we have developed a deep learning-based diagnosis system for metastatic breast cancer that can achieve high diagnostic accuracy as well as computational efficiency and mobile readiness suitable for an under-resourced environment. We evaluated 4 Convolutional Neural Network (CNN) architectures: MobileNetV2, VGG16, ResNet50 and ResNet101. The MobileNetV2-based diagnostic model outperformed the more complex VGG16, ResNet50 and ResNet101 models in diagnostic accuracy, model generalization, and model training efficiency. The ROC AUC of MobilenetV2 (0.933, 95% CI: 0.930, 0.936) was higher than VGG16 (0.911, 95% CI: 0.908, 0.915), ResNet50 (0.869, 95% CI: 0.866, 0.873), and ResNet101 (0.873, 95% CI: 0.869, 0.876). The time per inference step for the MobileNetV2 model (15 ms/step) was substantially lower than that of VGG16 (48 ms/step), ResNet50 (37 ms/step), and ResNet110 (56 ms/step). The visual comparisons between the model prediction and ground truth have demonstrated that the MobileNetV2 diagnostic models can identify very small cancerous nodes embedded in a large area of normal cells which is challenging for manual image analysis. Equally Important, the light weight MobleNetV2 models were computationally efficient and ready for mobile devices or devices of low computational power. These advances empower the development of a resource-efficient and high performing AI-based metastatic breast cancer diagnostic system that can adapt to under-resourced healthcare facilities in developing countries.
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Nearly 30 million (about 1 in 10) Americans have a rare disease. On average, rare disease patients wait 6 years for an accurate and definitive diagnosis and see as many as 12 specialists along their diagnostic journey. In this brief article, we highlight some of what is being done across patient care, medical education, policy, and innovation in order to improve the diagnostic and treatment journeys of rare disease patients. We hope that members of the medical education community will appreciate this call to action and engage in the rare disease space.
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OBJECTIVES: To report a case of ingested wire bristle embedded within the extrinsic musculature of the tongue requiring a transcervical approach for removal and to provide a revised algorithm for the management of ingested wire bristles. METHODS: The clinical record of 1 patient who ingested a grill brush wire bristle was reviewed. A literature review was also conducted to refine a treatment algorithm for managing ingested wire bristles. RESULTS: We present a case of a 53-year-old male who accidentally ingested a grill brush wire bristle. After multiple unsuccessful endoscopic attempts at removal, the wire bristle migrated deep into the extrinsic musculature of the tongue, necessitating a transcervical approach for adequate visualization and retrieval. CONCLUSIONS: This is the first case reported of a wire bristle migrating deep into the tongue musculature that was successfully removed via a transcervical approach. Our proposed algorithm provides a comprehensive approach to the management of ingested wire bristles, specifically in cases where endoscopic retrieval is not feasible.
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Corpos Estranhos , Laringe , Masculino , Humanos , Pessoa de Meia-Idade , Língua/cirurgia , Laringoscopia , Corpos Estranhos/cirurgia , AlgoritmosRESUMO
INTRODUCTION: Vocal fold atrophy and scar can lead to loss of normal superficial lamina propria, negatively affecting the vibratory function of the vocal fold. These changes can lead to dysphonia, vocal fatigue, decreased volume, and altered pitch. Treatment options for these conditions are limited. Platelet-rich plasma (PRP) consists of platelets, growth factors, and cytokines derived from the patient's own blood and is believed to activate tissue regeneration. The purpose of this study was to review the technical aspects of collecting PRP and injecting it into the vocal fold injection - based on our initial experience with this procedure. CASE: A patient with vocal fold scar was identified and enrolled in an ongoing prospective clinical trial study of a series of 4 monthly subepithelial vocal fold PRP injections, which was temporarily halted due to the COVID-19 pandemic. Patient underwent a single injection of autologous PRP into the left vocal fold. There were no adverse events during the study period. Subjective improvement in voice was noted at 1 month after injection with subsequent return to baseline over the next 4 months. Videostroboscopy performed on postinjection day 1 and day 7 and demonstrated no concerning exam changes. Compared to the preinjection baseline, the patient-reported voice-handicap index-10 (VHI-10) and voice catastrophization index were similar at 4 months following injection (20 to 20 and 4 to 3, respectively). Independent perceptual analysis of voice showed improvement at 4 months postinjection, compared to baseline consensus auditory-perceptual evaluation of voice 60 to 44. CONCLUSIONS: This preliminary report was part of a prospective trial investigating the use of PRP to treat vocal fold atrophy and scar. This work highlights the technical considerations for injecting PRP into the vocal fold. Planned prospective enrollment in this study will help to validate the safety and efficacy of PRP injections.
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COVID-19 , Disfonia , Doenças da Laringe , Plasma Rico em Plaquetas , Humanos , Atrofia/patologia , Cicatriz/patologia , COVID-19/patologia , Pandemias , Estudos Prospectivos , Resultado do Tratamento , Prega VocalRESUMO
OBJECTIVE: Vocal fold injection medialization (VFIM) is widely used as an initial treatment for unilateral vocal fold paralysis (UVFP). Current practices employ materials that share the limitation of temporary clinical effect from variable resorption rates. A novel silk protein microparticle-hyaluronic acid-based material (silk-HA) has demonstrated cellular infiltration and tissue deposition that may portend a durable medialization effect. We report on ≥12 months outcomes after VFIM with silk-HA. METHODS: Prospective open-label study of patients with UVFP that elected treatment with VFIM with silk-HA. Blinded experts rated laryngeal stroboscopic exams. RESULTS: Seventeen patients with UVFP underwent VFIM with silk-HA. Twelve of the 17 patients have ≥12 months follow-up. Seven patients demonstrated durable treatment benefit ≥12 months after injection with median improvement of 19 (p = 0.0156) in VHI-10. There was no significant change in VHI-10 between 1 and 12 months for these patients. Blinded ratings indicated that 5/7 patients with sustained improvements in VHI-10 exhibited complete or touch glottal closure at 12 months. Two of the seven patients exhibited a small (<1 mm) glottal gap at 12 months. Seven patients experienced initial benefit with later regression 3-4 months after injection. CONCLUSION: VFIM with silk-HA can offer durable improvement in voice-related outcomes for UVFP past 12 months. A subset of patients treated with silk-HA experienced early loss of effect around 3-4 months postinjection. Clinical factors predictive of sustained treatment response to silk-HA injection require further exploration. LEVEL OF EVIDENCE: 3 Laryngoscope, 2023.
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OBJECTIVE: To compare flexible distal-chip laryngoscopy (FDL) and rigid telescopic laryngoscopy (RTL) in image quality and diagnostic ability. STUDY DESIGN: Prospective cohort study; blinded comparison. METHODS: Eighteen normal adult subjects were recruited to undergo both FDL and RTL and normalized videos were recorded. Three blinded laryngologists compared the videos for color fidelity, illumination, resolution, and vascularity, and indicated superiority with FDL, RTL, or no difference. Raters also reported if an abnormality was seen and in which video it was better visualized. Videos for two subjects were repeated to assess intra-rater reliability, making 20 video comparisons across 3 raters for a total of 60 ratings. Differences in responses were analyzed via Mann-Whitney U and Pearson Χ2. Inter-rater reliability was assessed via Fleiss' kappa, and intra-rater reliability was assessed via percent agreement. RESULTS: RTL was rated superior in all categories of image quality (47 vs 5 vs 8, P < 0.01; 47 vs 7 vs 6, P < 0.01; 51 vs 5 vs 4, P<0.01; 44 vs 9 vs 7, P < 0.01, respectively). An abnormality was seen 33 times with both modalities and 6 times with RTL only. When seen with both modalities, visualization was superior in RTL compared with FDL (29 vs 4, P <0.01). CONCLUSIONS: There was significant superiority of RTL in all categories of image quality, with slight inter-rater agreement for color fidelity, resolution, and vascularity. RTL was also significantly better for visualization of abnormalities. These findings suggest superior image quality in RTL compared with FDL, but further research is required to determine if this difference is clinically significant.
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Laringoscopia , Iluminação , Adulto , Humanos , Laringoscopia/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Variações Dependentes do ObservadorRESUMO
OBJECTIVES: The aim of this study was to describe anesthetic management and perioperative complications in patients undergoing pulmonary vein isolation for the treatment of atrial fibrillation under general anesthesia using high-frequency jet ventilation. The authors also identified variables associated with longer ablation times in this patient cohort. DESIGN: A retrospective observational study. SETTING: The electrophysiology laboratory in a major university hospital. PARTICIPANTS: One hundred eighty-eight consecutive patients undergoing pulmonary vein isolation under general anesthesia with high-frequency jet ventilation. INTERVENTIONS: High-frequency jet ventilation was used as the primary mode of ventilation under general anesthesia. MEASUREMENTS AND MAIN RESULTS: High-frequency jet ventilation was performed successfully throughout the ablation procedure in 175 cases of the study cohort. The remaining 13 patients had to be converted to conventional positive-pressure ventilation because of high PaCO(2) or low PaO(2) on arterial blood gas measurements. Variables associated with a shorter ablation time included a higher ejection fraction (p = 0.04) and case volume performed by each electrophysiologist in the study group (p = 0.001). CONCLUSIONS: High-frequency jet ventilation is generally a safe technique that can be used in catheter ablation treatment under general anesthesia.
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Anestesia Geral/métodos , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Ventilação em Jatos de Alta Frequência/métodos , Veias Pulmonares/cirurgia , Idoso , Índice de Massa Corporal , Dióxido de Carbono/sangue , Feminino , Ventilação em Jatos de Alta Frequência/efeitos adversos , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Estudos RetrospectivosRESUMO
OBJECTIVE: The US Food and Drug Administration (FDA) regulates the marketing of medical devices based on the premarket approval (PMA) or 510(k) pathway. We investigated the relationship among the regulatory pathway of otolaryngologic devices, the number of recalls, and the recall characteristics. STUDY DESIGN: Retrospective cross-sectional analysis. SETTING: Publicly available FDA databases. METHODS: The FDA Ear, Nose, and Throat Devices Panel database was queried for 510(k) clearances and PMA approvals from 1976 to 2019. Device recalls from 2003 to 2019 were reviewed. Devices were then categorized by subspecialty, type, supporting evidence, and PMA supplement type. Logistic regression characterized the odds of recall for each device type and subspeciality. RESULTS: A total of 1061 (57.8%) 510(k) and 778 (42.3%) PMA device applications and modifications were approved. There were 120 (11.3%) recall events associated with 42 unique otolaryngologic devices cleared via the 510(k) pathway, as compared with 25 (3.2%) recall events for 5 unique PMA devices. 510(k) device approvals were more likely to be recalled than PMA device approvals (odds ratio, 3.67; 95% CI, 2.38-5.88; P < .0001). 510(k) surgical devices (odds ratio, 2.1; 95% CI, 1.1-4.4; P = .03) were more likely to be recalled than diagnostic devices. Devices designated for laryngology (70.0%) and general otolaryngology (25.0%) composed the majority of recalls. CONCLUSION: Otolaryngologic devices approved by the FDA via the 510(k) pathway exhibit a higher number of recalls than the PMA pathway. Given the balance between regulation and facilitating innovation, postmarket surveillance and ongoing regulatory improvements are critical to ensure optimal safety of medical devices.
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Aprovação de Equipamentos , Otolaringologia , Estados Unidos , Humanos , United States Food and Drug Administration , Recall de Dispositivo Médico , Vigilância de Produtos Comercializados , Estudos Retrospectivos , Estudos Transversais , FaringeRESUMO
OBJECTIVES/HYPOTHESIS: Prone positioning is frequently used in patients intubated for COVID-19-related lung injury to improve oxygenation. At our institution, we observed severe tongue edema develop in some of these patients. Hence, we sought to determine the incidence of tongue edema in this cohort and whether prone positioning was a risk factor associated with this complication. STUDY DESIGN: Retrospective cohort study. METHODS: A single-system retrospective cohort study of patients intubated for respiratory failure secondary to COVID-19 who subsequently developed clinically notable tongue edema from March 13 to July 5, 2020. RESULTS: 260 patients were intubated for COVID-19-related respiratory failure during the study period. 158 patients (60.8%) underwent at least one episode of proning. Twelve patients in total (4.6%) developed clinically significant tongue edema. Eleven of the twelve patients (91.7%) who developed tongue edema underwent proning prior to the development of edema. Prone positioning was associated with an increased incidence of tongue edema (odds ratio [OR] 7.56, 95% confidence interval [CI] 0.96-59.46, P = .027). In all proned patients who developed edema, this complication was noted during proning or shortly after supination (range, 0-4 days). Tongue edema was primarily managed with conservative measures; one patient required tracheostomy for definitive management. CONCLUSIONS: Tongue edema appears to develop in a subset of patients with COVID-19 who are intubated. It appears to be associated with prone positioning but is likely multifactorial in nature. Further investigation into its incidence and pathophysiology is warranted. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:287-289, 2022.
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COVID-19/complicações , Glossite/etiologia , Intubação Intratraqueal/efeitos adversos , Posicionamento do Paciente/efeitos adversos , Decúbito Ventral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Língua/patologiaRESUMO
Vocal fold mucous retention cysts are an important etiology of dysphonia and have classically been treated via microsurgical excision under general anesthesia. We present four cases that were treated with a novel technique of awake potassium-titanyl-phosphate laser-assisted marsupialization under local anesthesia. Reasons for in-office treatment included older age, medical comorbidities, and desire to avoid surgery/general anesthesia. No recurrences were observed and all patients had improved vocal quality, with a mean reduction in Voice Handicap Index-10 of 12.5. Hence, awake potassium-titanyl-phosphate laser treatment exhibits potential as a modality for addressing vocal fold mucous retention cysts in select patients with favorable outcomes.
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Cistos , Lasers de Estado Sólido , Cistos/cirurgia , Humanos , Lasers de Estado Sólido/uso terapêutico , Fosfatos , Potássio , Resultado do Tratamento , Prega Vocal/cirurgia , VigíliaRESUMO
OBJECTIVE: Patients with subglottic stenosis (SGS) present with varied degree of breathing complaints. The dyspnea index (DI) is a 10-question patient-reported outcome measure designed to measure the severity of upper airway obstruction. We set out to determine whether pulmonary function tests or clinician-reported degree of stenosis best predicted DI scores. METHODS: Thirty patients with SGS were retrospectively reviewed over a 6-year period. One visit from each patient was included. Data including peak expiratory flow rate (PEFR), body-mass index (BMI), clinician-reported degree of stenosis, and DI scores were reviewed. Multiple linear regression was performed to determine how degree of stenosis and PEFR % predicted the variation in DI score. RESULTS: PEFR % better predicted DI scores compared to degree of stenosis (partial correlation -0.32 vs 0.17). After stepwise elimination, PEFR % remained in the regression and was significantly associated with DI scores (F[1, 29] = 9.38, P = .005). BMI did not demonstrate a linear relationship with DI scores and was not included in the regression (r = -.02). The PEFR % unstandardized coefficient was -0.25 (95% CI: -0.42 to -0.08, P = .005). The model predicts that a 4% increase in the PEFR % results in a 1-point decrease in the DI score (95% CI: -1.68 to -0.32). CONCLUSION: This study suggests that pulmonary function tests may be a better in-office measure to substantiate the severity of symptoms in patients with SGS.