Objective: Three-dimensional printing technology is being employed in a variety of medical and surgical specialties to improve patient care and advance resident physician training. As the costs of implementing three-dimensional printing have declined, the use of this technology has expanded, especially within surgical specialties. This article explores the types of threedimensional printing available, highlights the benefits and drawbacks of each methodology, provides examples of how three-dimensional printing has been applied within the field of otolaryngology -head and neck surgery, discusses future innovations, and explores the financial impact of these advances.Data Sources: Articles were identified from PubMed and Ovid Medline.Review Methods: PubMed and Ovid Medline were queried for English articles published between 2011and 2016, including a few articles prior to this time as relevant examples. Search terms included: three-dimensional printing, 3D-printing, otolaryngology, additive manufacturing, craniofacial, reconstruction, temporal bone, airway, sinus, cost, and anatomic models.Conclusions: Three-dimensional printing has been used in recent years in otolaryngology for preoperative planning, education, prostheses, grafting, and reconstruction. Emerging technologies include the printing of tissue scaffolds for the auricle and nose, more realistic training models, and personalized implantable medical devices. Implications for Practice:After accounting for the upfront costs of three-dimensional printing, its utilization in surgical models, patient-specific implants, and custom instruments can reduce operating room time and thus decrease costs. Educational and training models provide an opportunity to better visualize anomalies, practice surgical technique, predict problems that might arise, and improve quality by reducing mistakes.3

Background: Olfactory dysfunction is a common symptom of chronic rhinosinusitis (CRS). We previously identified several cytokines potentially linked to smell loss, potentially supporting an inflammatory etiology for CRSassociated olfactory dysfunction. In the current study we sought to validate pa erns of olfactory dysfunction in CRS using hierarchical cluster analysis, machine learning algorithms, and multivariate regression.Methods: CRS patients undergoing functional endoscopic sinus surgery were administered the Smell Identification Test (SIT) preoperatively. Mucus was collected from the middle meatus using an absorbent polyurethane sponge and 17 inflammatory mediators were assessed using a multiplexed flow-cytometric bead assay. Hierarchical cluster analysis was performed to characterize inflammatory patterns and their association with SIT scores. The random forest approach was used to identify cytokines predictive of olfactory function. Results:One hundred ten patients were enrolled in the study. Hierarchical cluster analysis identified 5 distinct CRS clusters with statistically significant differences in SIT scores observed between individual clusters (p < 0.001). A majority of anosmic patients were found in a single cluster, which was additionally characterized by nasal polyposis (100%) and a high incidence of allergic fungal rhinosinusitis (50%) and aspirin-exacerbated respiratory disease (AERD) (33%). A random forest approach identified a strong association between olfaction and the cytokines interleukin (IL)-5 and IL-13. Multivariate modeling identified AERD, computed tomography (CT) score, and IL-2 as the variables most predictive of olfactory function. Conclusion:Olfactory dysfunction is associated with specific CRS endotypes characterized by severe nasal polyposis, tissue eosinophilia, and AERD. Mucus IL-2 levels, CT score, and AERD were independently associated with smell loss. C 2018 ARS-AAOA, LLC. How to Cite thisArticle: Morse JC, Shilts MH, Ely KA, et al. Pa erns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms. Int Forum Allergy Rhinol. 2019;9:255-264.O lfactory dysfunction is among the most common symptoms of chronic rhinosinusitus (CRS) with a prevalence of between 30% and 80%. 1, 2 Unfortunately, the etiology of CRS-associated olfactory dysfunction remains poorly understood. Olfactory loss in CRS has previously been attributed to an inability of odorants to effectively reach the olfactory cleft, due either to structural abnormalities or presence of nasal polyps. 3, 4 Recent research has suggested that sinonasal inflammation may directly or indirectly affect olfactory neurons and olfactory function. 5 In animal models, certain cytokines have the ability to adversely affect olfactory neuron function, turnover, and regeneration. 5-8 An association between olfactory cleft cytokine levels and olfactory function has been partially

OBJECTIVE Craniopharyngiomas have historically been resected via transcranial microsurgery (TCM). In the last 2 decades, the extended endoscopic endonasal (transtuberculum) approach to these tumors has become more widely accepted, yet there remains controversy over which approach leads to better outcomes. The purpose of this study is to determine whether differences in outcomes were identified between TCM and extended endoscopic endonasal approaches (EEEAs) in adult patients undergoing primary resection of suprasellar craniopharyngiomas at a single institution. METHODS A retrospective review of all patients who underwent resection of their histopathologically confirmed craniopharyngiomas at the authors' institution between 2005 and 2015 was performed. Pediatric patients, revision cases, and patients with tumors greater than 2 standard deviations above the mean volume were excluded. The patients were divided into 2 groups: those undergoing primary TCM and those undergoing a primary EEEA. Preoperative patient demographics, presenting symptoms, and preoperative tumor volumes were determined. Extent of resection, tumor histological subtype, postoperative complications, and additional outcome data were obtained. Statistical significance between variables was determined utilizing Student t-tests, chi-square tests, and Fisher exact tests when applicable. RESULTS After exclusions, 21 patients satisfied the aforementioned inclusion criteria; 12 underwent TCM for resection while 9 benefitted from the EEEA. There were no significant differences in patient demographics, presenting symptoms, tumor subtype, or preoperative tumor volumes; no tumors had significant lateral or prechiasmatic extension. The extent of resection was similar between these 2 groups, as was the necessity for additional surgery or adjuvant therapy. CSF leakage was encountered only in the EEEA group (2 patients). Importantly, the rate of postoperative visual improvement was significantly higher in the EEEA group than in the TCM group (88.9% vs 25.0%; p = 0.0075). Postoperative visual deterioration only occurred in the TCM group (3 patients). Recurrence was uncommon, with similar rates between the groups. Other complication rates, overall complication risk, and additional outcome measures were similar between these groups as well. CONCLUSIONS Based on this study, most outcome variables appear to be similar between TCM and EEEA routes for similarly sized tumors in adults. The multidisciplinary EEEA to craniopharyngioma resection represents a safe and compelling alternative to TCM. The authors' data demonstrate that postoperative visual improvement is statistically more likely in the EEEA despite the increased risk of CSF leakage. These results add to the growing evidence that the EEEA may be considered the approach of choice for resection of select confined primary craniopharyngiomas without significant lateral extension in centers with experienced surgeons. Further prospective, multiinstitutional collaboration is needed to power studies capable of fully evaluating indications and appropriate approaches for craniopharyngiomas.

Background: Potential effects of aging on chronic rhinosinusitis (CRS) pathophysiology have not been well defined, but may have important ramifications given a rapidly aging U.S. and world population. Objective:The goal of the current study was to determine whether advanced age is associated with specific inflammatory CRS endotypes or immune signatures.Methods: Seventeen mucus cytokines and inflammatory mediators were measured in 147 CRS patients. Hierarchical cluster analysis was used to identify and characterize inflammatory CRS endotypes as well as determine whether age was associated with specific immune signatures.Results: A CRS endotype with a pro-inflammatory, neutrophilic immune signature was enriched with older patients. In the overall cohort, patients 60 years and older had elevated mucus levels of IL-1β, IL-6, IL-8, and TNF-α when compared to their younger counterparts.

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