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BACKGROUND: Empty nose syndrome (ENS) is a poorly understood, debilitating condition affecting a minority of patients who underwent nasal airway surgery, most commonly following inferior turbinate surgery. Few publications have demonstrated middle turbinate resection (MTR) causing ENS, but MTR is still considered a potential cause of ENS. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) is validated for ENS diagnosis, with ENS6Q ≥ 11 considered highly suggestive of ENS. The purpose of this multicenter study was to determine the incidence of patients with ENS6Q ≥ 11 following subtotal MTR during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing preoperative and postoperative ENS6Q scores. METHODS: A multi-institutional prospective cohort study (8 US institutions) was conducted on patients who underwent bilateral subtotal MTR during ESS for CRSwNP. Preoperative and postoperative ENS6Q scores were compared after at least 12 months of postoperative follow-up. RESULTS: Of 110 patients, mean age was 51.6 years and 59.1% were male. Mean follow-up was 14.5 ± 2.5 months (range 12.1-22.3 months). Mean preoperative and postoperative ENS6Q were 7.7 and 2.2, respectively, demonstrating a mean 5.5 point decrease postoperatively (p < 0.0001). At final follow-up, no patient had an ENS6Q ≥ 11. Of note, 20% of patients had preoperative ENS6Q scores ≥11, but all decreased to <11 postoperatively. CONCLUSIONS: Based on prospective multicenter data over 1-2 years postoperatively, subtotal MTR for CRSwNP never led to ENS6Q scores ≥11, and patients experienced significant decreases in ENS6Q postoperatively. Subtotal MTR during ESS for CRSwNP was, therefore, unlikely to cause ENS even with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.
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KEY POINTS: Chitosan is a promising drug delivery vector for therapeutics owing to its biocompatibility. Once crosslinked with chitosan, prolonged drug release was noted regardless of hydrophilicity. Hydrophilic drugs may require different strategies to obtain a sustained release profile.
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OBJECTIVES: Previously, we developed a novel double-coated sinus stent containing ciprofloxacin (inner layer) and azithromycin (outer layer) (CASS), but released drug concentrations were found to be insufficient for clinical usage. Our objectives are to improve drug release of CASS and assess safety and pharmacokinetics in rabbits. METHODS: Dip coating was used to create the CASS with 2 mg ciprofloxacin and 5 mg azithromycin. A uniformed double coating was assessed with scanning electron microscopy (SEM), and the release patterns of both drugs and lactate dehydrogenase (LDH) assay were evaluated over 14 days in vitro. Safety, tolerability, and pharmacokinetics of the CASS were tested in rabbits through insertion into the maxillary sinus and evaluated with nasal endoscopy, CT scans, histology, blood counts and chemistries, and in vivo drug release. RESULTS: SEM confirmed the uniformity of the dual coating of ciprofloxacin and azithromycin, and thickness (µm) was found to be 14.7 ± 2.4 and 28.1 ± 4.6, respectively. The inner coated ciprofloxacin showed a sustained release over 14 days (release %) when soaked in saline solution (day 7, 86.2 ± 3.4 vs. day 14,99.2 ± 5.1). In vivo analysis showed that after 12 days, 78.92 ± 7.67% of CP and 84.12 ± 0.45% of AZ were released into the sinus. There were no significant differences in body weight, white blood cell counts, and radiographic changes before and after CASS placement. No significant histological changes were observed compared to the contralateral control side. CONCLUSION: Findings suggest that the CASS is an effective method for delivering therapeutic levels of antibiotics. Further studies are needed to validate efficacy in a preclinical sinusitis model. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:3953-3959, 2024.
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Antibacterianos , Azitromicina , Ciprofloxacina , Rinossinusite , Animais , Coelhos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Azitromicina/farmacocinética , Doença Crônica , Ciprofloxacina/administração & dosagem , Ciprofloxacina/efeitos adversos , Ciprofloxacina/farmacocinética , Modelos Animais de Doenças , Stents Farmacológicos/efeitos adversos , Seio Maxilar/cirurgia , Seio Maxilar/diagnóstico por imagem , Microscopia Eletrônica de Varredura , Rinossinusite/tratamento farmacológicoRESUMO
Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.
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Encéfalo , Cognição , Treinamento Olfativo , Humanos , Transtornos do Olfato/terapia , OlfatoRESUMO
Background/Aims: Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. Methods: This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. Results: Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib; 2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400-600 mg (9.6 months). Conclusions: Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.
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Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Antineoplásicos/uso terapêutico , Estudos Retrospectivos , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Resultado do TratamentoRESUMO
KEY POINTS: Duplicated images in research articles erode integrity and credibility of biomedical science. Forensic software is necessary to detect figures with inappropriately duplicated images. This analysis reveals a significant issue of inappropriate image duplication in our field.
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INTRODUCTION: Hypoxia due to sinus obstruction is a major pathogenic mechanism leading to sinusitis. The objective of the current study is to define the electrophysiologic characteristics of hypoxia in vitro and in vivo. METHODS: Cystic fibrosis bronchoepithelial cells expressing wild-type cystic fibrosis transmembrane conductance regulator (CFTR) and human sinonasal epithelial cells were exposed to 1% or atmospheric O2 for 24 h. Time-dependent production of cytoplasmic free radicals was measured. Cells were subjected to Ussing chamber and patch clamp technique where CFTR currents were recorded in whole-cell and cell-attached mode for single channel studies. Indices of mucociliary transport (MCT) were measured using micro-optical coherence tomography. In a rabbit hypoxic maxillary sinus model, tissue oxygenation, relative mRNA expression of HIF-1α, pH, sinus potential difference (SPD), and MCT were determined. RESULTS: Ussing chamber (p < 0.05), whole-cell (p < 0.001), and single channel patch-clamp (p < 0.0001) showed significant inhibition of Cl- currents in hypoxic cells. Cytoplasmic free radicals showed time-dependent elevation peaking at 4 h (p < 0.0001). Airway surface liquid (p < 0.0001), periciliary liquid (p < 0.001), and MCT (p < 0.01) were diminished. Co-incubation with the free radical scavenger glutathione negated the impact of hypoxia on single channel currents and MCT markers. In sinusitis rabbits, mucosa exhibited low tissue oxygenation (p < 0.0001), increased HIF1α mRNA (p < 0.05), reduced pH (p < 0.01), and decreased MCT (p < 0.001). SPD measurements demonstrated markedly diminished transepithelial Cl- transport (p < 0.0001). CONCLUSION: Hypoxia induces severe CFTR dysfunction via free radical production causing reduced MCT in vitro and in vivo. Improved oxygenation is critical to reducing the impact of persistent mucociliary dysfunction.
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INTRODUCTION: Cystic fibrosis (CF) airway disease is characterized by thick mucus and impaired mucociliary transport (MCT). Loss of functional cystic fibrosis transmembrane receptor (CFTR) leads to acidification and oxidation of airway surface mucus. Replacing bicarbonate (HCO3 - ) topically fails due to rapid reabsorption and neutralization, while the scavenging antioxidant, glutathione sulfhydryl (GSH), is also rapidly degraded. The objective of this study is to investigate GSH/NaHCO3 nanoparticles as novel strategy for CF airway disease. METHODS: GSH/NaHCO3 poly (lactic-co-glycolic acid) nanoparticles were tested on primary CF (F508del/F508del) epithelial cultures to evaluate dose-release curves, surface pH, toxicity, and MCT indices using micro-optical coherence tomography. In vivo tests were performed in three rabbits to assess safety and toxicity. After 1 week of daily injections, histopathology, computed tomography (CT), and blood chemistries were performed and compared to three controls. Fluorescent nanoparticles were injected into a rabbit with maxillary sinusitis and explants visualized with confocal microscopy. RESULTS: Sustained release of GSH and HCO3 - with no cellular toxicity was observed over 2 weeks. Apical surface pH gradually increased from 6.54 ± 0.13 (baseline) to 7.07 ± 0.10 (24 h) (p < 0.001) and 6.87 ± 0.05 at 14 days (p < 0.001). MCT, ciliary beat frequency, and periciliary liquid were significantly increased. When injected into the maxillary sinuses of rabbits, there were no changes to histology, CT, or blood chemistries. Nanoparticles penetrated rabbit sinusitis mucus on confocal microscopy. CONCLUSION: Findings suggest that GSH/NaHCO3 - nanoparticles are a promising treatment option for viscous mucus in CF and other respiratory diseases of mucus obstruction such as chronic rhinosinusitis.
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Olfaction is one of the five basic human senses, and it is known to be one of the most primitive senses. The sense of olfaction may have been critical for human survival in prehistoric society, and although many believe its importance has diminished over time, it continues to have an impact on human interaction, bonding, and propagation of the species. Even if we are unaware of it, the sense of smell greatly affects our lives and is closely related to overall quality of life and health. Nonetheless, olfaction has been neglected from a scientific perspective compared to other senses. However, olfaction has recently received substantial attention since the loss of smell and taste has been noted as a key symptom of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Studies investigating olfaction loss in association with coronavirus disease 2019 (COVID-19) have revealed that olfactory dysfunction can be both conductive and sensorineural, possibly causing structural changes in the brain. Olfactory training is an effective treatment for olfactory dysfunction, suggesting the reorganization of neural associations. A reduced ability to smell may also alert suspicion for neurodegenerative or psychiatric disorders. Here, we summarize the basic knowledge that we, as otorhinolaryngologists, should have about the sense of smell and the peripheral and central olfactory pathways for managing and helping patients with olfactory dysfunction.
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BACKGROUND: We previously discovered that Korean red ginseng aqueous extract (RGAE) potentiates the TMEM16A channel, improved mucociliary transport (MCT) parameters in CF nasal epithelia in vitro, and thus could serve as a therapeutic strategy to rescue the MCT defect in cystic fibrosis (CF) airways. The hypothesis of this study is that RGAE can improve epithelial Cl- secretion, MCT, and histopathology in an in-vivo CF rat model. METHODS: Seventeen 4-month old CFTR-/- rats were randomly assigned to receive daily oral control (saline, n = 9) or RGAE (Ginsenosides 0.4mg/kg/daily, n = 8) for 4 weeks. Outcomes included nasal Cl- secretion measured with the nasal potential difference (NPD), functional microanatomy of the trachea using micro-optical coherence tomography, histopathology, and immunohistochemical staining for TMEM16a. RESULTS: RGAE-treated CF rats had greater mean NPD polarization with UTP (control = -5.48 +/- 2.87 mV, RGAE = -9.49 +/- 2.99 mV, p < 0.05), indicating, at least in part, potentiation of UTP-mediated Cl- secretion through TMEM16A. All measured tracheal MCT parameters (airway surface liquid, periciliary liquid, ciliary beat frequency, MCT) were significantly increased in RGAE-treated CF rats with MCT exhibiting a 3-fold increase (control, 0.45+/-0.31 vs. RGAE, 1.45+/-0.66 mm/min, p < 0.01). Maxillary mucosa histopathology was markedly improved in RGAE-treated cohort (reduced intracellular mucus, goblet cells with no distention, and shorter epithelial height). TMEM16A expression was similar between groups. CONCLUSION: RGAE improves TMEM16A-mediated transepithelial Cl- secretion, functional microanatomy, and histopathology in CF rats. Therapeutic strategies utilizing TMEM16A potentiators to treat CF airway disease are appropriate and provide a new avenue for mutation-independent therapies.
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Fibrose Cística , Humanos , Ratos , Animais , Depuração Mucociliar , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Uridina Trifosfato/metabolismo , Uridina Trifosfato/uso terapêutico , Células Epiteliais/metabolismo , Transporte de ÍonsRESUMO
KEY POINTS: A long-duration pain block did not decrease postoperative pain or opioid consumption. Extended sinus procedures do not lead to additional postoperative pain or opioid consumption.
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Anestesia , Seios Paranasais , Humanos , Analgésicos Opioides/uso terapêutico , Endoscopia/métodos , Seios Paranasais/cirurgia , Anestesia/métodos , Dor Pós-Operatória/tratamento farmacológicoRESUMO
Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR channel is responsible for the transport of the anions (chloride and bicarbonate) across airway epithelia. Patients with CF have thick mucus, disrupted mucociliary transport, and chronic bacterial infections in the upper and lower airways. In this article, the pathophysiology of CFTR dysfunction and its impact on the united airway are reviewed as well as the treatment strategies for patients with chronic rhinosinusitis-related CF and acquired CFTR dysfunction.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/genética , Depuração Mucociliar , Transporte de Íons , Cloretos/metabolismoAssuntos
Seio Frontal , Doenças dos Seios Paranasais , Fraturas Cranianas , Humanos , Endoscopia , Qualidade de VidaRESUMO
BACKGROUND: The escalating negative impact of climate change on our environment has the potential to result in significant morbidity of rhinologic diseases. METHODS: Evidence based review of examples of rhinologic diseases including allergic and nonallergic rhinitis, chronic rhinosinusitis, and allergic fungal rhinosinusitis was performed. RESULTS: The lower socioeconomic population, including historically oppressed groups, will be disproportionately affected. CONCLUSIONS: We need a systematic approach to improve healthcare database infrastructure and funding to promote diverse scientific collaboration to address these healthcare needs.
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Hipersensibilidade , Rinite , Sinusite , Humanos , Mudança Climática , Rinite/epidemiologia , Sinusite/epidemiologia , Doença CrônicaRESUMO
BACKGROUND: Spontaneous cerebrospinal fluid (sCSF) leaks develop from pressure erosion due to idiopathic intracranial hypertension, treatment of which is paramount to preventing recurrence. Direct measurements of intracranial pressure (ICP) for monitoring response to treatment via lumbar drain (LD) or ventriculostomy are invasive and have risks. The objectives of this study are to determine whether ultrasonographic measurements of optic nerve sheath diameter (ONSD) correlate with LD ICP in patients with sCSF leaks undergoing treatment, and whether ONSDs are larger in patients with sCSF leaks than controls. METHODS: Subjects with sCSF leaks and controls were prospectively recruited. ONSD, sex, and body mass index (BMI) were analyzed. For sCSF leak subjects, ultrasonography was performed at the time of LD opening and each pressure check postoperatively, including the acetazolamide response. In control patients, measurements were obtained at the time of surgery. Pearson's correlation between ONSD and ICP was performed. RESULTS: Subjects with sCSF leaks (n = 9, age 52.4 ± 9.5, all female) and controls (n = 8, age 60.1 ± 14.8, two females) had significantly different BMIs, 38.4 ± 8.1 vs. 29.2 ± 4.8, t(15) = 2.793, p = 0.014. ONSD was strongly correlated with ICP measurements (r = 0.583, p = 0.002). However, percentage change in ONSD and ICP measurements were more strongly correlated (r = 0.733, p < 0.001). Patients with sCSF leaks had significantly higher ONSDs than controls, 0.63 cm ± 0.044 vs. 0.56 cm ± 0.074, t(15) = 2.329, p = 0.034. CONCLUSION: ONSD significantly correlated with ICP in sCSF leak patients and was wider in sCSF leak subjects than controls. Ultrasonography has utility in monitoring the ICP response to acetazolamide.
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Hipertensão Intracraniana , Pseudotumor Cerebral , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Pressão Intracraniana/fisiologia , Nervo Óptico/diagnóstico por imagem , Hipertensão Intracraniana/diagnóstico por imagem , Acetazolamida/uso terapêutico , Pseudotumor Cerebral/diagnóstico por imagem , UltrassonografiaRESUMO
Introduction: Inverted papillomas of the middle ear are extremely rare tumors that carry an increased risk of recurrence and malignant transformation. There are currently 59 cases of middle ear inverted papillomas reported in the literature. The objective in this study was to systematically evaluate outcomes regarding middle ear inverted papillomas with respect to demographics, anatomical tumor sites, malignant transformation status, recurrence rate and HPV status. Study Design: Retrospective case series and systematic review. Methods: A systematic review was completed on June 25, 2020 with a search strategy including PubMed, Embase, Scopus and Google Scholar. This revealed 181 articles. Full-text review was completed, and 66 articles were included. 115 articles were eliminated due to duplication of articles from databases, article titles not applicable to the aims of the systematic review and articles describing inverted papilloma of body sites other than middle ear. Discussion: Thirty-one cases of primary inverted papillomas of the middle ear were found in the literature with an additional 26 cases of secondary tumors. Four case reports did not specify primary versus secondary. The malignant transformation rate was 34.4% with a 53.6% recurrence rate. Treatment of middle ear inverted papillomas is primarily surgical with adjuvant radiation therapy considered for patients with recurrence or malignant transformation. Frequent clinical follow up of these patients is critical due to the increased rate of recurrence and malignant transformation. Conclusion: Inverted papillomas of the middle ear are rare tumors that carry a high risk of recurrence and malignant transformation necessitating complete resection and frequent clinical follow up.
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BACKGROUND: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced-based review with recommendations (EBRR) for fundamental management principles of CF CRS. METHODS: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence. RESULTS: We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS). CONCLUSION: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder.