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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, 2024.
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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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INTRODUCTION: Mental health disorders (MHD), including substance abuse, have been associated with aortic dissection (AD). Aneurysmal degeneration in the residual untreated aorta after both open and endovascular treatment is not uncommon in AD. Thus, diligent long-term follow-up is necessary and MHD may play a role in treatment plan and surveillance. The impact of MHD on management, outcomes and follow-up after AD treatment is unknown and here we sought to evaluate these associations. METHODS: A retrospective review was performed on all patients diagnosed with Stanford Type A and B dissections from 2008 to 2018 at a tertiary referral center. MHD was defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Patient demographics, procedural characteristics, and outcomes were analyzed. RESULTS: A total of 649 non-traumatic aortic dissections were identified in the study timeframe. The cohort consisted of 51% Type A (n = 334) dissection and 49% Type B (n = 315) dissection. Mental health disorders were present in 49.3% of the cohort. Notably, the timing of MHD diagnosis relative to development of AD is unknown in the majority of patients. Within the Type A population, a MHD was present in 50.6% (N = 162) of patients, of which the most common indication for MHD was the presence of antidepressant or antipsychotic medication (28.6%). In patients with Type A dissections, the presence of a MHD did not significantly affect the rate of index hospitalization intervention (68%) or long-term mortality (12.5% in patients with a MHD). Within the Type B population, a MHD was present in 49.4% (n = 158) of patients, of which the most common indication for MHD was the presence of antidepressant or antipsychotic medication (30.5%). In patients with Type B dissections, the presence of a MHD did not significantly affect the rate of index hospitalization intervention (50.3% in patients with a MHD) or long-term mortality (10.1% in patients with a MHD). The overall participation in follow-up care was not significantly decreased based on the presence of a MHD compared to those without a MHD (1.66 ± 2.16 years vs. 1.68 ± 2.20 years, P = 0.93). CONCLUSION: MHD is more prevalent in AD patients than in the general population, but demonstrating a causal relationship between MHD and development/progression of AD is challenging. Despite a high prevalence of MHD in AD patients, in-hospital mortality and follow-up compliance was similar to non-MHD patients.
