Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin and azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in the sinuses could mitigate side effects and improve drug concentrations at the infected site. This study was aimed to evaluate the efficacy of the novel ciprofloxacin-azithromycin sinus stent (CASS) in vitro. Methods: The CASS was created by coating ciprofloxacin (hydrophilic, inner layer) and azithromycin (hydrophobic, outer layer) onto a biodegradable poly-L-lactic acid (PLLA) stent. In vitro evaluation included: 1) assessment of drug coating stability within the stent using scanning electron microscopy (SEM); 2) determination of ciprofloxacin and azithromycin release kinetics; and 3) assessment of anti-biofilm activities against Pseudomonas aeruginosa. Results: The ciprofloxacin nanoparticle-suspension in the inner layer was confirmed by zeta potential. Both ciprofloxacin (60 µg) and azithromycin (3mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 +/-11.

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Objective Spontaneous cerebrospinal fluid (CSF) leaks represent a unique subset of skull base pathology and require distinctive management. Perioperative evaluation and management of intracranial hypertension are essential in preventing further erosion of the skull base and development of recurrent leak. The objective of this study is to evaluate the safety and utility of an expedited protocol for recording and managing intracranial hypertension following endoscopic repair of spontaneous CSF leaks. Methods Prospectively collected data was reviewed in patients undergoing endoscopic repair of spontaneous CSF leaks between January 2017 and March 2020. A standard intracranial pressure monitoring protocol was compared to an expedited protocol (EP), and data regarding the two groups was compared for leak location, short‐term success of skull base repair, complications, hospital length of stay, and cost‐based analysis. Results Fifty‐five patients (standard protocol, n = 28 vs. EP, n = 27) were included in the study. Leak location was similar between cohorts, with the lateral recess being the most common locations in both groups (37.9% vs. 40.6%; P = .90). Postoperative complications (3.6% vs. 7.4%; P = .53) and ventriculoperitoneal shunt rate (32.1% vs. 22.2%; P = .41) were similar among cohorts. There was no difference in lumbar drain complications (0% vs. 7.4%; P = .14) or recurrent leak (7.1% vs. 0%; P = .16). Length of stay was shorter in the EP group [median(interquartile range): 3(1) vs. 2 (1); P < .01]. Total hospital charges were similar between groups (median (USD/$1,000): 83.57 ± 49.58 vs. 83.93 ± 46.11; P = .18). Conclusion An expedited monitoring protocol shortened hospital stay without increased risk of complications. Level of Evidence III Laryngoscope, 131:E408–E412, 2021

Background: Chronic rhinosinusitis (CRS) is characterized by complex bacterial infections with persistent inflammation. Based on our rabbit model of sinusitis, blockage of sinus ostia generated a shift in microbiota to a predominance of mucin degrading microbes (MDM) with acute inflammation at 2 weeks. This was followed by conversion to chronic sinus inflammation at 3 months with a robust increase in pathogenic bacteria (e.g., Pseudomonas). MDMs are known to produce acid metabolites [short chain fatty acids (SCFA)] that have the potential to stimulate pathogen growth by offering a carbon source to non-fermenting sinus pathogens (e.g., Pseudomonas). The objective of this study is to evaluate the concentrations of SCFA within the mucus and its contribution to the growth of P. aeruginosa. Methods: Healthy and sinusitis mucus from the rabbit model were collected and co-cultured with the PAO1 strain of P. aeruginosa for 72 h and colony forming units (CFUs) were determined with the targeted quantification of three SCFAs (acetate, propionate, butyrate). Quantification of SCFAs in healthy and sinusitis mucus from patients with P. aeruginosa was also performed via high performance liquid chromatography. Results: To provide evidence of fermentative activity, SCFAs were quantified within the mucus samples from rabbits with and without sinusitis. Acetate concentrations were significantly greater in sinusitis mucus compared to controls (4.13 ± 0.53 vs. 1.94 ± 0.44 mM, p < 0.01). After 72 h of co-culturing mucus samples with PAO1 in the presence of mucin medium, the blue-green pigment characteristic of Pseudomonas was observed throughout tubes containing sinusitis mucus. CFUs were higher in cultures containing mucus samples from sinusitis (8.4 × 10 9 ± 4.8 × 10 7) compared to control (1.4 × 10 9 ± 2.0 × 10 7) or no mucus (1.5 × 10 9 ± 2.1 × 10 7) (p < 0.0001). To provide evidence of fermentative activity in human CRS with P. aeruginosa, the presence of SCFAs in human Cho et al. Anaerobes in Recalcitrant CRS mucus was analyzed and all SCFAs were significantly higher in CRS with P. aeruginosa compared to controls (p < 0.05). Conclusion: Given that SCFAs are solely derived from bacterial fermentation, our evidence suggests a critical role for mucin-degrading bacteria in generating carbonsource nutrients for pathogens. MDM may contribute to the development of recalcitrant CRS by degrading mucins, thus providing nutrients for potential pathogens like P. aeruginosa.

Background We recently developed a ciprofloxacin and azithromycin sinus stent CASS to target recalcitrant infections in chronic rhinosinusitis CRS The objective of this study was to evaluate the anti-inflammatory activity of azithromycin released from the CASS and assess the impact on the integrity and function of primary human sinonasal epithelial cells HSNECs Methods Pseudomonas aeruginosa lipopolysaccharide LPS-stimulated HSNECs were treated with azithromycin and/or ciprofloxacin at concentrations attainable from CASS release Interleukin-IL-secretion was quantified by enzyme-linked immunosorbent assay ELISA Epithelial integrity transepithelial resistance TEER paracellular permeability fluorescein isothiocyanate-labeled dextran lactate dehydrogenase LDH assays and function ciliary beat frequency CBF were also evaluated Results Azithromycin significantly reduced secreted ILfrom P aeruginosa LPS-stimulated HSNECs at all concentrations tested mean ± standard deviation control = ± ng/mL azithromycin µg/mL = ± ng/mL azithromycin μg/mL = ± azithromycin μg/mL = ± ng/mL p < Co-incubation with azithromycin μg/mL and ciprofloxacin μg/mL in LPS-stimulated HSNECs also displayed a significant reduction in secreted IL-when compared to P aeruginosa LPS alone co-treatment = ± ng/mL P aeruginosa LPS = ± ng/mL p < The drugs did not negatively impact TEER paracellular permeability LDH release or CBF indicating retention of cell integrity and function Conclusion Azithromycin decreased P aeruginosa LPS ILproduction in HSNECs at drug concentrations attainable with sustained release of azithromycin from the CASS In addition to antibacterial activity anti-inflammatory properties of the CASS should provide further benefit for patients with recalcitrant CRS © 2020 ARS-AAOA, LLC.

Objective Frontal sinus osteomyelitis is a severe complication which can result from chronic rhinosinusitis, trauma, or as a complication of reconstruction or obliteration of the frontal sinus. The objective of the current study is to evaluate the contemporary management of frontal sinus osteomyelitis in light of recent advancements in endoscopic surgical techniques. Methods Review of a prospectively collected database of patients with frontal sinus pathology was performed from 2008–2020. Data from individuals with frontal sinus osteomyelitis was collected including demographics, etiology, surgical technique, adjunctive medical treatments, complications, and clinical follow up. Results Sixteen patients (average age 48.3, range 8–84) were included in the study. An open approach was utilized in 6 patients (2 osteoplastic flaps, 3 Reidel procedures, 1 cranialization). Seven patients underwent completely endoscopic approaches (3 Draf IIB, 4 Draf III), while 3 individuals had combined procedures (Lynch with Draf III, osteoplastic flap + Draf III, fistula excision + Draf IIb). All patients received 6 weeks of antibiotics. Average clinical follow up was 24.4 months with no patients requiring revision procedures. Conclusion Endoscopic, endoscopic-assisted, and open approaches were utilized successfully in the current series of patients with osteomyelitis of the anterior table of the frontal sinus. While the progression of endoscopic techniques allows an additional surgical treatment option, it is important to select patients appropriately as open procedures continue to have an important role in the treatment algorithm.