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KEY POINTS: Using 3D modeling, we studied the influence of orbital tumor morphology on post-operative outcomes. Orbital tumor volume did not influence postoperative complication rates. Less spherical tumors may be correlated with a more extensive surgical approach.
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KEY POINTS: Penetrating orbital trauma from marine creatures, especially needlefish, should be considered after injuries sustained in open water. Advances in endoscopic sinus surgery have enabled surgeons to remove certain orbital foreign bodies through endoscopic endonasal approaches. 3D segmentation is a valuable pre-operative tool in complex endoscopic orbital cases.
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One of the primary obstacles in treating central nervous system (CNS) disorders lies in the limited ability of disease-modifying drugs to cross the blood-brain barrier (BBB). Our previously described Minimally Invasive Nasal Depot (MIND) technique has proven successful in delivering various drugs to the brain in rat models via a trans-olfactory mucosal approach. In this study, we introduce a novel Minimally Invasive Nasal Infusion (MINI) delivery approach for administering ovalbumin, a model protein, utilizing a programmable infusion pump (iPRECIO SMP-310R) in a mouse model. This research highlights the significant role of olfactory mucosa in nose-to-brain delivery, with an efficacy of nearly 45% compared to intracerebroventricular (ICV) administration. This demonstrates its potential as an alternative procedure for treating CNS diseases, offering a greater safety profile relative to the highly invasive clinical routes traditionally adopted for CNS drug delivery.
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Administración Intranasal , Ovalbúmina , Animales , Ovalbúmina/administración & dosificación , Sistemas de Liberación de Medicamentos , Masculino , Ratones , Encéfalo/metabolismo , Bombas de Infusión , Barrera Hematoencefálica/metabolismo , Ratones Endogámicos C57BLRESUMEN
KEY POINTS: Data on current practice patterns for the management of chronic rhinosinusitis with nasal polyps, including which medications are deemed by otolaryngologists to better manage patient symptoms, are limited. This study demonstrated that contemporary practice patterns are largely consistent with published clinical consensus statements. Off-label nasal steroid irrigations and dupilumab are the most commonly used topical and systemic therapies for chronic rhinosinusitis with nasal polyps, respectively.
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KEY POINTS: The angled tip and small size of the crescent blade provide versatility for its use in a variety of endonasal procedures. The crescent blade enables cutting along 180° from the tip, ensuring a tangential cut through the mucosa, which is important for flap viability. The disposable nature of the blade ensures that it is always sharp, allowing for its use in mucosal and cartilaginous cuts.
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OBJECTIVE: Identifying the biomarkers for uncontrolled chronic rhinosinusitis (CRS) is important for directing treatment decisions. Eosinophilia has been reported to be involved in the poor disease control of CRS and mucus eosinophil-derived neurotoxin (EDN) is potentially a biomarker of intense eosinophil activation. This study aimed to assess the relationship between mucus EDN levels, disease severity, and degree of CRS control. METHODS: A total of 150 adult patients with CRS and 25 healthy controls were prospectively enrolled. The nasal mucus and tissue specimens were collected to analyze EDN levels. Disease severity was assessed by Lund-Mackay score and 22-item Sino-Nasal Outcome Test (SNOT-22) score. Five CRS symptom severities during the prior month (nasal blockage, rhinorrhoea/postnasal drip, facial pain/pressure, smell, sleep disturbance or fatigue), use of rescue medications in the last six months, and the presence of diseased mucosa on nasal endoscopy were obtained. Consistent with the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 CRS control criteria, uncontrolled CRS was defined as meeting at least three items. RESULTS: 40% of patients with CRS presented with uncontrolled status. Patients with uncontrolled CRS had significantly higher nasal mucus EDN levels (P = 0.010), percentage of blood eosinophil (P = 0.015), SNOT-22 score (P < 0.001), Lund-Mackay score (P = 0.008), and a more eosinophilic dominant phenotype of CRS (P < 0.001) than patients with controlled CRS. Furthermore, mucus EDN levels were positively correlated with blood eosinophils (r = 0.541, P = 0.005), SNOT-22 score (r = 0.460, P = 0.021), and Lund-Mackay score (r = 0.387, P = 0.039). Mucus EDN levels were the significant parameter related to uncontrolled CRS in multivariable analysis after adjusting for patient demographics and comorbidities (odds ratio = 1.323; P = 0.004). CONCLUSIONS: Mucus EDN levels may be a potential biomarker for identifying the CRS control status.
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Biomarcadores , Neurotoxina Derivada del Eosinófilo , Moco , Rinitis , Sinusitis , Humanos , Sinusitis/complicaciones , Sinusitis/metabolismo , Rinitis/metabolismo , Rinitis/complicaciones , Masculino , Femenino , Enfermedad Crónica , Persona de Mediana Edad , Adulto , Moco/metabolismo , Neurotoxina Derivada del Eosinófilo/metabolismo , Biomarcadores/metabolismo , Estudios Prospectivos , Estudios de Casos y Controles , Índice de Severidad de la Enfermedad , Mucosa Nasal/metabolismo , Prueba de Resultado Sino-Nasal , Anciano , RinosinusitisRESUMEN
Neurological disorders are a diverse group of conditions that pose an increasing health burden worldwide. There is a general lack of effective therapies due to multiple reasons, of which a key obstacle is the presence of the blood-brain barrier, which limits drug delivery to the central nervous system, and generally restricts the pool of candidate drugs to small, lipophilic molecules. However, in many cases, these are unable to target key pathways in the pathogenesis of neurological disorders. As a group, RNA therapies have shown tremendous promise in treating various conditions because they offer unique opportunities for specific targeting by leveraging Watson-Crick base pairing systems, opening up possibilities to modulate pathological mechanisms that previously could not be addressed by small molecules or antibody-protein interactions. This potential paradigm shift in disease management has been enabled by recent advances in synthesizing, purifying, and delivering RNA. This review explores the use of RNA-based therapies specifically for central nervous system disorders, where we highlight the inherent limitations of RNA therapy and present strategies to augment the effectiveness of RNA therapeutics, including physical, chemical, and biological methods. We then describe translational challenges to the widespread use of RNA therapies and close with a consideration of future prospects in this field.
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Enfermedades del Sistema Nervioso Central , Nanopartículas , Humanos , ARN/metabolismo , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Barrera Hematoencefálica/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Terapia Genética/métodosRESUMEN
OBJECTIVE: Though the endoscopic endonasal approach (EEA) is a widely accepted treatment for skull base tumors, the specific use of EEA for olfactory groove meningiomas (OGMs) is debated, with variable outcomes reported in the literature. We review the surgical results of OGM resections for one surgeon including the operative approach, surgical nuances, and outcomes, with a focus on factors relating to patient selection which favor EEA over transcranial approaches. METHODS: We retrospectively reviewed thirteen cases of endoscopic endonasal resection of olfactory groove meningiomas. Patient characteristics, clinical characteristics, surgical outcomes, and complications were analyzed. Extent of resection was determined based on volumetric analysis of pre- and postoperative MRI. RESULTS: Anatomic characteristics that render a tumor difficult to access fully are lateral extension beyond the mid-orbit and anterior extension to the falx. Simpson Grade I resection was achieved in 11/13 (84.6 %) cases. Mean pre-operative tumor volume was 8.99 cm3 (range 2.19-16.79 cm3), and 92 % of tumors were WHO grade I. We demonstrate 2 cases of smell preservation, possible with small unilateral tumors and tumors that are confined to either the anterior or posterior portion of the cribriform plate. The post-operative CSF leak rate was 7.7 %, without prophylactic lumbar CSF drainage. The mortality rate was 7.7 % (n = 1) after infectious complications following CSF leak. CONCLUSIONS: Endoscopic endonasal resection of olfactory groove meningiomas is an effective and safe operative method with outcomes and complication rates comparable to transcranial approaches. Key considerations include careful patient selection and familiarity with technical nuances of endoscopic endonasal approach for this specific tumor type.
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Neoplasias Meníngeas , Meningioma , Neoplasias de la Base del Cráneo , Humanos , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Meningioma/patología , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/cirugía , Nariz/cirugía , Nariz/patología , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/diagnóstico por imagen , Neoplasias de la Base del Cráneo/cirugía , Resultado del TratamientoRESUMEN
Clinical studies have consistently shown that neurodegenerative diseases (NDs) such as Parkinson's disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease show absent or low levels of brain-derived neurotrophic factor (BDNF). Despite this relationship between BDNF and ND, only a few ND animal models have been able to recapitulate the low BDNF state, thereby hindering research into the therapeutic targeting of this important neurotrophic factor. In order to address this unmet need, we sought to develop a reproducible model of BDNF reduction by inducing traumatic brain injury (TBI) using a closed head momentum exchange injury model in mature 9-month-old male and female rats. Head impacts were repetitive and varied in intensity from mild to severe. BDNF levels, as assessed by ELISA, were significantly reduced in the hippocampus of both males and females as well as in the substantia nigra of males 12 days after mild TBI. However, we observed significant sexual dimorphism in multiple sequelae, including magnetic resonance imaging-determined vasogenic edema, astrogliosis (GFAP-activation), and microgliosis (Iba1 activation). This study provides an opportunity to investigate the mechanism of BDNF reduction in rodent models and provides a reliable paradigm to test BDNF-targeted therapeutics for the treatment of ND.
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Conmoción Encefálica , Lesiones Traumáticas del Encéfalo , Animales , Femenino , Masculino , Ratas , Conmoción Encefálica/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Sustancia Negra/metabolismoRESUMEN
BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.
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Neoplasias de Cabeza y Cuello , Hipersensibilidad , Neoplasias de los Senos Paranasales , Humanos , Calidad de Vida , Neoplasias de los Senos Paranasales/terapia , Neoplasias de los Senos Paranasales/patologíaRESUMEN
OBJECTIVE: The EuroQol 5-Dimension (EQ-5D) is a general health survey that is quick to administer, widely used, and directly convertible to health utility values (HUV). We aim to describe the five-year EQ-5D outcomes among patients who undergo surgical treatment for chronic rhinosinusitis (CRS). STUDY DESIGN: Prospective observational cohort study. METHODS: Patients with CRS completed the EQ-5D questionnaire preoperatively and annually for five years following endoscopic sinus surgery. Paired t-tests and McNemar's tests were used to compare preoperative and postoperative scores. Mixed-effects modeling was used for multivariate analysis. RESULTS: Among 1296 patients enrolled in our study, 812 (74.7%) completed the postoperative survey at one year and 336 (38.9%) completed it at five years. There was a significant and sustained reduction of patients reporting pain/discomfort (74.9% vs. 58.0%, p < 0.001) and anxiety/depression (49.6% vs. 38.1%, p = 0.01) out to five years. Frequency of problems reported in the usual activity domain decreased at one year and was sustained through year four (30.6% vs 19.7%, p = 0.003). After multivariable modeling, female gender (p = 0.02), prior sinus surgery (p = 0.01), tobacco use (p = 0.038), headaches (p = 0.013), allergies (p = 0.001), diabetes (p = 0.022), hypertension (p = 0.036), higher preoperative SNOT-22 score (p < 0.001), and a lower preoperative Lund-Mackay score (p < 0.001) were associated with significantly worse EQ-5D HUV over time. Similarly, a worse EQ-5D Visual Analog Scale (VAS) over time was associated with allergies (p = 0.03), diabetes (p < 0.001), hypertension (p = 0.04), higher preoperative SNOT-22 score (p < 0.001), and prior sinus surgery (p < 0.001). CONCLUSION: Patients with chronic rhinosinusitis experience significant sustained improvements in health-related quality of life up to five years after ESS as measured by the EQ-5D instrument. LEVEL OF EVIDENCE: Level 2 Laryngoscope, 134:2592-2601, 2024.
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Endoscopía , Calidad de Vida , Rinitis , Sinusitis , Humanos , Masculino , Femenino , Sinusitis/cirugía , Endoscopía/métodos , Estudios Prospectivos , Rinitis/cirugía , Persona de Mediana Edad , Enfermedad Crónica , Adulto , Resultado del Tratamiento , Encuestas y Cuestionarios , Factores de Tiempo , Estudios de Seguimiento , AncianoRESUMEN
OBJECTIVE: The objective of this study was to analyze advantages and disadvantages of mucus and serum for biomarker analysis. METHODS: This study includes prospective study of 61 CRS with nasal polyps patients who were followed over 24 months and over nine time points after functional endoscopic sinus surgery. At each time points, the nasal polyp score (NPS) was assessed and mucus as well as serum was collected. Selected were measured in mucus and serum. Mean, standard deviation and variance, undetectable values, and the correlation of the biomarkers to the NPS over time and to early recurrences were calculated, and the effect of surgery on the biomarkers was assessed. Additionally, the diurnal rhythm of all biomarkers was measures in order to assure stable biomarker values during sampling times. RESULTS: All biomarkers showed stable values during sampling times. Serum biomarker levels displayed higher percentages of undetectable values compared to mucus biomarkers. Mucus periostin (p < 0.001, r = 0.89), mucus IgE (p < 0.001, r = 0.51), serum periostin (p < 0.001, r = 0.53), mucus CST1 (p < 0.001, r = 0.27), and serum IgE (p < 0.01, r = -0.18) were the best marker and medium combinations to track the NPS over time and to predict recurrences. Mucus serpinF2 was negatively correlated and predicted early recurrences (p = 0.026, R2 = 0.015). CONCLUSIONS: Serum and mucus both represent viable mediums for "liquid biopsies." The most promising biomarker/medium combinations over time to track disease severity were mucus periostin, mucus IgE, serum periostin, mucus CST1, and serum IgE. Mucus serpinF2 was the best biomarker to predict early recurrences.
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BACKGROUND: Acoustic resonance therapy (ART) is a novel vibrational treatment that delivers patient-specific resonant frequency acoustic energy to the sinonasal cavities. In a pilot study, ART was effective for the acute treatment of nasal congestion. We conducted a sham-controlled randomized trial to validate the efficacy of ART when administered daily for 2 weeks. METHODS: A total of 52 adult patients were enrolled in a multi-center, randomized, double-blinded, sham-controlled, interventional study evaluating ART administered by a vibrational headband. Patients received either active treatment or a non-therapeutic sham treatment twice daily over 2 weeks. Clinical endpoints were the average change in nasal congestion sub-score of the Total Nasal Symptom Score (TNSS) and the average change in composite TNSS. RESULTS: ART resulted in a significantly greater mean change in the nasal congestion sub-score compared to sham (-0.87 [95% confidence interval [CI] -1.11, -0.62] vs. -0.44 [95% CI -0.64, -0.23], p = 0.008). ART also resulted in a significantly greater reduction in the composite TNSS versus sham, (-2.85 [95% CI -3.85, -1.85], vs. -1.32 [95% CI -2.27, -0.36], p = 0.027). The response rate, determined by a nasal congestion sub-score minimal clinically important difference of 0.23, was 80.8% for ART and 46.2% for sham, with an adjusted risk ratio of 1.95 (95% CI 1.26, 3.02, p = 0.003) in favor of ART. Safety endpoints showed no adverse events. CONCLUSION: ART is a safe and effective non-pharmacologic alternative for the treatment of nasal congestion.
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Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the paranasal sinuses which represents a significant health burden due to its widespread prevalence and impact on patients' quality of life. As the molecular pathways driving and sustaining inflammation in CRS become better elucidated, the diversity of treatment options is likely to widen significantly. Nanotechnology offers several tools to enhance the effectiveness of topical therapies, which has been limited by factors such as poor drug retention, mucosal permeation and adhesion, removal by epithelial efflux pumps and the inability to effectively penetrate biofilms. In this review, we highlight the successful application of nanomedicine in the field of CRS therapeutics, discuss current limitations and propose opportunities for future work.
Chronic sinusitis is a common inflammatory condition of the sinuses, which affects patients' quality of life and consumes significant healthcare resources. It is primarily treated with corticosteroids, a type of medication that reduces inflammation, as a nasal spray or taken orally. Nasal sprays are preferred, to minimize side effects elsewhere in the body. Recently, another class of drugs 'biologic agents' has been approved for a subtype of chronic sinusitis that causes polyps (grape-like swellings of the sinus lining). However, a lasting cure is elusive, because inflammation frequently returns once these medications are stopped. As our understanding of what causes chronic sinusitis improves, researchers are seeking therapies that more accurately target the cause of inflammation, rather than broadly suppressing all types of inflammation using corticosteroids. The use of nanotechnology allows the design of drugs to overcome various challenges in treating chronic sinusitis, potentially enabling more accurate delivery of drugs into the sinuses, improving drugs' ability to remain on the sinus lining and penetrate it, reducing the amount of drug lost due to the action of outflow pumps and overcoming additional defenses built up by bacteria when they form thick films. Here, we describe how nanomedicine has been used to develop drugs for chronic sinusitis, discuss current limitations and propose opportunities for future work.
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Senos Paranasales , Rinitis , Sinusitis , Humanos , Calidad de Vida , Rinitis/tratamiento farmacológico , Rinitis/metabolismo , Sinusitis/tratamiento farmacológico , Sinusitis/metabolismo , Senos Paranasales/metabolismo , Enfermedad Crónica , NanotecnologíaAsunto(s)
Neoplasias Orbitales , Humanos , Neoplasias Orbitales/cirugía , Nariz , Órbita/cirugía , EndoscopíaRESUMEN
BACKGROUND: Eosinophils are associated with olfactory dysfunction in chronic rhinosinusitis (CRS) and eosinophil-derived neurotoxin (EDN) is a sensitive marker of intense eosinophil activation. This study aimed to analyze olfactory cleft mucus and olfactory mucosa EDN levels and their association with olfactory dysfunction in CRS. METHODS: We prospectively recruited 150 patients with CRS electing endoscopic sinus surgery and 25 healthy controls. Both superior turbinate biopsy specimens and olfactory cleft mucus were collected to analyze EDN levels. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, and olfactory cleft endoscopy scale (OCES) were obtained. Multivariable logistic regression analysis was applied to analyze the predictability of EDN levels for olfactory dysfunction in CRS. RESULTS: Chronic rhinosinusitis with olfactory dysfunction presented significantly higher olfactory mucosa (p = 0.016) and olfactory cleft mucus (p < 0.001) EDN levels than CRS without olfactory dysfunction. Mucus EDN levels were positively correlated with blood eosinophils (r = 0.625, p = 0.002), olfactory cleft CT scores (r = 0.738, p < 0.001), and OCES (r = 0.605, p = 0.004) in CRS. Furthermore, mucus EDN levels were significantly negatively correlated with threshold, discrimination, and identification (TDI) (r = -0.688), olfactory threshold (r = -0.606), olfactory discrimination (r = -0.608), and olfactory identification (r = -0.697) scores. After adjusting for patient demographics and comorbidities, mucus EDN levels were significantly associated with olfactory dysfunction in CRS (odds ratio = 2.162; p = 0.027). Mucus EDN levels showed a significantly better performance for predicting olfactory dysfunction than blood eosinophil counts (area under the curve, 0.873 vs. 0.764, p = 0.024). CONCLUSION: Olfactory cleft mucus EDN level may be a better biomarker for predicting olfactory dysfunction in CRS than blood eosinophil counts.
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Trastornos del Olfato , Rinitis , Sinusitis , Humanos , Eosinófilos/patología , Neurotoxina Derivada del Eosinófilo , Rinitis/patología , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/complicaciones , Sinusitis/cirugía , Enfermedad Crónica , Anosmia , MocoRESUMEN
OBJECTIVE: To identify the impact of gender on the clinical outcomes of endoscopic sinus surgery (ESS) through the comparison of quality of life measures in female and male patients who undergo surgical treatment for chronic rhinosinusitis (CRS). STUDY DESIGN: Prospective observational cohort study. METHODS: Patients with CRS completed the 22-item Sino-Nasal Outcome Test (SNOT-22) and EuroQol 5-Dimension Survey (EQ-5D) preoperatively and annually for 5 years following ESS. Health utility values (HUV) were calculated from EQ-5D scores. Comparisons of cohort characteristics were performed with chi-square and t-tests. A multivariable linear mixed effects model evaluated changes in SNOT-22 and HUV over time by gender. RESULTS: Among the 1268 patients (54% female) enrolled, 789 and 343 completed postoperative surveys at one and 5 years, respectively. Preoperatively, females experienced more severe symptoms: mean SNOT-22 score (51.1 ± 20.9 female vs. 44.7 ± 20.0 male, p < 0.001) and HUV (0.80 ± 0.14 female vs. 0.84 ± 0.11 male, p < 0.001). These gender differences were resolved by year one postoperatively (SNOT-22: p = 0.083; HUV: p = 0.465). Two years after surgery, however, females reported more severe symptoms (SNOT-22: 25.6 ± 20.7 female vs. 21.5 ± 17.4 male, p = 0.005; HUV: 0.88 ± 0.12 female vs. 0.90 ± 0.11 male, p = 0.018), a difference that persisted at year five. These gender-related differences remained after adjusting for age, race, ethnicity, nasal polyps, history of prior ESS, and smoking status (p < 0.001). Within-subject improvement was comparable between genders (SNOT-22: p = 0.869; HUV: p = 0.611). CONCLUSION: Females with CRS reported more severe symptoms both before and 5 years after surgery compared to their male counterparts. Understanding the mechanism behind these gender-related differences is important for optimizing CRS treatment. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3319-3326, 2023.
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Rinitis , Sinusitis , Humanos , Masculino , Femenino , Calidad de Vida , Estudios Prospectivos , Rinitis/cirugía , Sinusitis/cirugía , Enfermedad Crónica , Endoscopía/métodos , Resultado del TratamientoRESUMEN
Verapamil is a calcium channel blocker that holds promise for the therapy of chronic rhinosinusitis (CRS) with and without nasal polyps. The verapamil-induced side effects limit its tolerated dose via the oral route, underscoring the usefulness of localized intranasal administration. However, the challenge to intranasal administration is mucociliary clearance, which diminishes localized dose availability. To overcome this challenge, verapamil was loaded into a mucoadhesive cationic poly(ethylene glycol)-modified (PEGylated) liposomal carrier. Organotypic nasal explants were exposed to verapamil liposomes under flow conditions to mimic mucociliary clearance. The liposomes resulted in significantly higher tissue residence compared with the free verapamil control. These findings were further confirmed in vivo in C57BL/6 mice following intranasal administration. Liposomes significantly increased the accumulation of verapamil in nasal tissues compared with the control group. The developed tissue-retentive verapamil liposomal formulation is considered a promising intranasal delivery system for CRS therapy.
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Liposomas , Sinusitis , Animales , Ratones , Liposomas/uso terapéutico , Verapamilo , Polietilenglicoles/uso terapéutico , Ratones Endogámicos C57BL , Administración Intranasal , Sinusitis/tratamiento farmacológico , Administración TópicaRESUMEN
BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs. METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class. RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05). CONCLUSION: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs.
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Hemangioma Cavernoso , Neoplasias Orbitales , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Neoplasias Orbitales/cirugía , Neoplasias Orbitales/patología , Estudios Retrospectivos , Resultado del Tratamiento , Nariz/cirugía , Endoscopía , Hemangioma Cavernoso/cirugíaRESUMEN
Nucleic acid-based therapeutic molecules including small interfering RNA (siRNA), microRNA(miRNA), antisense oligonucleotides (ASOs), messenger RNA (mRNA), and DNA-based gene therapy have tremendous potential for treating diseases in the central nervous system (CNS). However, achieving clinically meaningful delivery to the brain and particularly to target cells and sub-cellular compartments is typically very challenging. Mediating cell-specific delivery in the CNS would be a crucial advance that mitigates off-target effects and toxicities. In this review, we describe these challenges and provide contemporary evidence of advances in cellular and sub-cellular delivery using a variety of delivery mechanisms and alternative routes of administration, including the nose-to-brain approach. Strategies to achieve subcellular localization, endosomal escape, cytosolic bioavailability, and nuclear transfer are also discussed. Ultimately, there are still many challenges to translating these experimental strategies into effective and clinically viable approaches for treating patients.