Nasal Nitric Oxide as a Biomarker in the Diagnosis and Treatment of Sinonasal Inflammatory Diseases: A Review of the Literature.

OBJECTIVE: To critically review the literature on nasal nitric oxide (nNO) and its current clinical and research applicability in the diagnosis and treatment of different sinonasal inflammatory diseases, including acute bacterial rhinosinusitis (ABRS), allergic rhinitis (AR), and chronic rhinosinusitis (CRS). METHODS: A search of the PubMed database was conducted to include articles on nNO and sinonasal diseases from January 2003 to January 2020. All article titles and abstracts were reviewed to assess their relevance to nNO and ABRS, AR, or CRS. After selection of the manuscripts, full-text reviews were performed to synthesize current understandings of nNO and its applications to the various sinonasal inflammatory diseases. RESULTS: A total of 79 relevant studies from an initial 559 articles were identified using our focused search and review criteria. nNO has been consistently shown to be decreased in ABRS and CRS, especially in cases with nasal polyps. While AR is associated with elevations in nNO, nNO levels have also been found to be lower in AR cases with higher symptom severity. The obstruction of the paranasal sinuses is speculated to be an important variable in the relationship between nNO and the sinonasal diseases. Treatment of these diseases appears to affect nNO through the reduction of inflammatory disease burden and also mitigation of sinus obstruction. CONCLUSION: nNO has been of increasing interest to researchers and clinicians over the last decade. The most compelling data for nNO as a clinical tool involve CRS. nNO can be used as a marker of ostiomeatal complex patency. Variations in measurement techniques and technology continue to impede standardized interpretation and implementation of nNO as a biomarker for sinonasal inflammatory diseases.

Management of complicated acute sinusitis in the setting of concurrent COVID-19.

PURPOSE: Intraorbital and intracranial complications of acute bacterial rhinosinusitis require timely medical and surgical treatment to prevent the development of long-term neurologic sequelae. The era of Coronavirus Disease-2019 (COVID-19) has complicated the management of complicated acute rhinosinusitis, especially when patients have concurrent acute sinusitis and COVID-19 infection. This case series aims to highlight the clinical course of pediatric patients at a single tertiary pediatric hospital with concurrent complicated bacterial rhinosinusitis and COVID-19. MATERIALS AND METHODS: A search of pediatric patients treated for COVID-19 and complications from acute sinusitis was performed using billing records for the year 2020-2021 at a single pediatric tertiary hospital. Data regarding presentation, management, microbiology, and hospital course was collected for review. RESULTS: A total of 6 patients with complicated bacterial sinusitis in the setting of COVID-19 infection were included. All patients were initially managed with medical therapy, consisting of systemic antibiotics, but 3 of these patients ultimately required surgical intervention. Cultures from the cohort grew Staphylococcus aureus, streptococcus intermedius, streptococcus constellatus or Prevotella species. All patients experienced clinical improvements and were eventually discharged home with oral antibiotics. CONCLUSION: COVID-19 continues to be an unusual disease especially for the pediatric population. Concurrent complicated acute rhinosinusitis and COVID-19 appear to have higher rates of surgical requirement in the pediatric population. COVID-19 safety precautions have influenced management practices for patients with severe bacterial rhinologic infections. While there may be an association between complicated bacterial rhinosinusitis and COVID-19 infection, further research is necessary to determine a true correlation.

A review of phase III clinical trials of US FDA-approved biologic therapies for chronic rhinosinusitis with nasal polyposis.

Chronic rhinosinusitis with nasal polyposis is a heterogenous disease with complex underlying pathophysiologic mechanisms. Biologics have been proven to be an effective add-on therapeutic option in severe and/or refractory cases. Currently, dupilumab, omalizumab and mepolizumab have phase III data to support their use in these patients and have received approval from the United States Food and Drug Administration specifically for the treatment of nasal polyposis. Each of these biologics has shown its ability to reduce nasal polyp size and improve nasal congestion/obstruction and sense of smell, but additional research is needed to directly compare the efficacy and safety of the different biologic agents for different nasal polyposis endotypes.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a complex disease that has many different causes. Biological therapies have been proven to be effective when added on to standard treatment in severe and/or cases that are not responsive to initial treatment. Currently, dupilumab, omalizumab and mepolizumab have data supporting their use in such patients and have received approval by the United States Food and Drug Administration for the treatment of CRSwNP. Each of these biologics has shown its ability to reduce nasal polyp size and improve nasal congestion/obstruction and sense of smell, but additional research is needed to directly compare the efficacy and safety of the different biologic agents for different CRSwNP subtypes.

Primary cervical ganglioneuroblastoma, nodular subtype.

Primary cervical ganglioneuroblastoma is rare and reports of its subtypes are limited. This case series describes two pediatric patients with the nodular subtype of primary cervical ganglioneuroblastoma with lymphatic spread. Clinical course, diagnosis, and management of this rare tumor are discussed with emphasis on the importance of including neuroblastic tumors in the differential diagnosis of pediatric neck masses. We also report the use of nerve monitoring of the recurrent laryngeal nerve as a surrogate for the vagus nerve during a pediatric neck dissection.

Variations in utilization and clinical outcomes for endoscopic sphenopalatine artery ligation and endovascular arterial embolization in a single multi-hospital network.

PURPOSE: Endoscopic sphenopalatine artery ligation (ESPAL) and endovascular arterial embolization (EAE) are increasingly common treatment options for patients with refractory epistaxis. The objective of this study was to compare the utilization pattern and clinical outcomes between these interventions within our single multi-hospital network. MATERIALS AND METHODS: A retrospective study of all patients undergoing ESPAL and/or EAE within any of the hospitals in a single healthcare network between 2008 and 2017 was conducted. We compared differences in procedure utilization with various hospital characteristics. Secondarily, we evaluated clinical outcomes and costs associated with each procedure. RESULTS: Forty-three ESPAL and 33 EAE procedures were performed across 7 hospitals, with the majority of procedures being performed at teaching institutions (65% and 91%, p = .013). The majority of both interventions were performed in larger hospitals and EAE patients were more likely to undergo inter-hospital transfer compared to ESPAL patients (48.5% and 16.3%, p = .02). Success rates for ESPAL and EAE were comparable (95% and 93%); however, the median direct cost of treatment for EAE was significantly higher than the cost for ESPAL ($12984.89 and $5002.02, p < .0001). CONCLUSIONS: The majority of both ESPAL and EAE interventions were performed at teaching and larger hospitals. Transfers occurring prior to EAE may have been due to the limited availability of interventional radiology services, and likely contributed to the increased cost of treatment. ESPAL is a known cost-effective management strategy and should be considered early in treatment algorithms of refractory epistaxis.

Intraoperative Applications of Topical Corticosteroid Therapy for Chronic Rhinosinusitis.

OBJECTIVES: To provide an overview of recent techniques and technologies for the application of topical corticosteroid therapy immediately following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). METHODS: A comprehensive search in the PubMed and Google Scholar databases was conducted to identify publications between January 2000 and December 2019 detailing clinical trials that have evaluated the efficacy and safety of intraoperative applications of topical corticosteroids for CRS. RESULTS: A total of 21 articles, all of which highlight a variety of corticosteroid-infused products, including Propel corticosteroid-eluting stents, NasoPore, Merocel, SinuBand, calcium alginate, and bioresorbable gel-type products, are included for review. Propel stents are the only devices that have achieved level 1A evidence in terms of efficacy and have data to support their safety. The remaining products have shown mixed results in terms of efficacy and safety. CONCLUSION: A wide range of techniques and technologies have been introduced to enhance the topical delivery of corticosteroids into the neosinuses after ESS for CRS. Regarding efficacy, there is level 1A evidence to support the use of Propel stents. Most of the remaining strategies show some degree of efficacy. Direct comparisons across the different strategies are limited owing to the varied uses of delivery vectors, corticosteroid choices, and doses of corticosteroids. Propel stents and SinuBand have sufficient data to support systemic and ocular safety, whereas the remaining products have limited data to support their safety.

Pharmaceutical inhibition of mTOR in the common marmoset: effect of rapamycin on regulators of proteostasis in a non-human primate.

BACKGROUND: Inhibition of mechanistic target of rapamycin (mTOR) has emerged as a viable means to lengthen lifespan and healthspan in mice, although it is still unclear whether these benefits will extend to other mammalian species. We previously reported results from a pilot experiment wherein common marmosets (Callithrix jacchus) were treated orally with rapamycin to reduce mTOR signaling in vivo in line with previous reports in mice and humans. Further, long-term treatment did not significantly alter body weight, daily activity, blood lipid concentrations, or glucose metabolism in this cohort. METHODS: In this study, we report on the molecular consequences of rapamycin treatment in marmosets on mechanisms that regulate protein homeostasis (proteostasis) in vivo. There is growing appreciation for the role of proteostasis in longevity and for the role that mTOR plays in regulating this process. Tissue samples of liver and skeletal muscle from marmosets in our pilot cohort were assessed for expression and activity of components of the ubiquitin-proteasome system, macroautophagy, and protein chaperones. RESULTS: Rapamycin treatment was associated with increased expression of PSMB5, a core subunit of the 20S proteasome, but not PSMB8 which is involved in the formation of the immunoproteasome, in the skeletal muscle and liver. Surprisingly, proteasome activity measured in these tissues was not affected by rapamycin. Rapamycin treatment was associated with an increased expression of mitochondria-targeted protein chaperones in skeletal muscle, but not liver. Finally, autophagy was increased in skeletal muscle and adipose, but not liver, from rapamycin-treated marmosets. CONCLUSIONS: Overall, these data show tissue-specific upregulation of some, but not all, components of the proteostasis network in common marmosets treated with a pharmaceutical inhibitor of mTOR.