Nicholas R. Rowan

Background: Olfactory dysfunction (OD) is associated with diminished quality of life (QOL), depressive symptoms, and cognitive decline, and emerging evidence suggests that olfactory training (OT) may mitigate both OD and its broader impacts. This review aims to systematically evaluate the effects of OT on QOL, depression, and cognitive outcomes. Methods: PubMed, Embase, Cochrane, Scopus, and Web of Science were searched for studies published between 1990 and 2025. PRISMA guidelines were followed for study screening and data extraction. Studies evaluating the effects of OT on QOL, depressive symptoms, or cognitive function were included. Random‐effects models were used to pool within‐group standardized mean changes (SMC) and between‐group standardized mean differences (SMD). Results: Fifty‐one studies met inclusion criteria, with 19 included in quantitative synthesis. OT was associated with improvement in olfactory‐specific QOL (Questionnaire of Olfactory Disorders [QOD] SMC = 1.29; 95% CI [0.04–2.55]). Among controlled trials, OT produced a significant advantage in QOD improvement over no‐OT (QOD SMD = 0.40; 95% CI: 0.04–0.76). OT was associated with a modest improvement in global cognitive performance (Montreal Cognitive Assessment mean difference = 0.65; 95% CI [0.35, 0.94]), but no significant effect was observed on depressive symptoms (Beck Depression Inventory SMC = −0.20; 95% CI: [−0.55, 0.14]). Conclusions: OT is associated with improved olfactory‐specific QOL and cognitive benefits. These findings support the potential of OT as a low‐cost intervention to support the multifaceted challenges experienced by individuals with OD, while highlighting the need for adequately powered studies to clarify its effectiveness for treating OD‐associated depression.

Background: The proportion of otolaryngology trainees pursuing fellowship has increased alongside rapid expansion in rhinology fellowship programs. Contemporary data evaluating trainee motivations, expectations, and outcomes remain limited. This study assesses contemporary data evaluating trainee motivations, expectations, and outcomes among US rhinology fellows over a 7‐year period. Methods: A combined prospective and retrospective survey study was conducted using questionnaires administered to incoming and outgoing fellows at US rhinology fellowship programs from 2018 to 2025. Surveys evaluated motivations, procedural comfort, research expectations, career plans, and overall satisfaction. Responses were analyzed descriptively. Results: A total of 241 responses were analyzed (124 incoming, 117 outgoing). The primary motivation for fellowship was to enhance surgical skills and clinical decision‐making, with fewer respondents citing research or mentorship. Fellows reported high comfort with standard endoscopic sinus procedures but lower confidence with advanced skull base and rhinoplasty techniques. Protected research time was inconsistent, with 16%–45% of graduating fellows reporting none, differing from incoming expectations. Interest in a 2‐year fellowship was low (29% incoming vs. 18% outgoing). While 71.8% of incoming fellows anticipated academic careers, 64.1% ultimately entered academic practice. Overall satisfaction was high, with 86.3% reporting that fellowship met expectations. Reported shortcomings included limited skull base exposure, reduced surgical autonomy, inadequate billing/coding training, and insufficient research time. Conclusion: Rhinology fellowship trainees primarily pursue subspecialty training to enhance surgical skills and clinical decision‐making. Although training is overwhelmingly perceived as meeting expectations, meaningful gaps persist between anticipated and actual experiences, particularly in protected academic time, exposure to advanced procedures, and non‐clinical skill development.

Human papillomavirus (HPV)–related multiphenotypic sinonasal carcinoma (HMSC) is a rare neoplasm characterized by a paradoxical clinical course. Despite its high-grade histologic features, HMSC exhibits an unexpectedly indolent clinical behavior, marked by frequent local recurrences but limited metastatic potential. We report the first case of HMSC metastasis to the liver with the earliest known distant progression. A 53-year-old male who presented with unilateral epistaxis was found to have T4aN0M0 HPV35-positive HMSC of the left maxillary sinus, with erosion into the orbital floor. He underwent induction chemotherapy, endoscopic resection with negative margins, and adjuvant chemoradiation. He did well until surveillance PET-CT at 10 months revealed asymptomatic hepatic metastases confirmed by biopsy. He was treated with transarterial chemoembolization and pembrolizumab before developing locoregional recurrence involving the orbital apex and cavernous sinus 5 months later. Several case reports demonstrate HMSC's potential for aggressive behavior, including intracranial extension and rapid recurrence. However, distant metastases (DM) are rare, with only three documented cases of pulmonary metastases and one digital metastasis, occurring years after initial treatment. We present the first reported case of HMSC with metastasis to the liver, marking the earliest known distant recurrence. This case challenges the current paradigm by highlighting HMSC's potential for aggressive systemic progression. Molecularly, this tumor harbored high-risk HPV35, a rarely reported subtype. Despite HMSC's typically indolent course, this case underscores the importance of vigilant surveillance to detect early DM and guide therapeutic management.

Introduction: Previous studies suggest a relationship between olfactory impairment and frailty but have focused on odor identification (I), potentially overlooking odor threshold sensitivity (T), and discrimination (D). Our objective was to characterize the relationship between olfactory subcomponents and frailty status by establishing optimal thresholds for these measures. Methods: We conducted a prospective study assessing frailty using the physical frailty phenotype and olfactory function using the Sniffin’ Sticks Test in older adults. T, D, I (range 0–16 for each) and the composite threshold, discrimination, and identification (TDI) score (range −0 to 48) were evaluated using receiver operating characteristic analysis and area under the curve (AUC) measures. Results: This study included 103 participants, with a mean age of 82.8 ± 5 years, 56% ( n = 58) female, and 89% ( n = 92) white. Frail participants had significantly lower T (8.5 ± 3.3 vs. 4.4 ± 3.0), D (11.4 ± 2.0 vs. 8.1 ± 2.5), I (11.9 ± 2.4 vs. 9.2 ± 2.9), and TDI scores (31.9 ± 5.9 vs. 21.7 ± 6.6) compared to non‐frail individuals ( p < 0.001 for all). TDI demonstrated the strongest ability to distinguish between frail and non‐frail participants (AUC = 0.86), followed by D (AUC = 0.85), T (AUC = 0.82), and I (AUC = 0.78). The optimal cutoff for D was a score of 10, yielding a sensitivity of 73% and specificity of 88%. Cutoff values were also established for T (score = 6), I (score = 12), and TDI (score = 29). Conclusion: Identified cutoff values may enhance risk stratification and inform clinical interventions. Across subdomains, discrimination scores may yield more information than identification. Additional studies in larger samples will be necessary to investigate subdomain differences.

Mechanisms of tumorigenesis in sinonasal squamous cell carcinoma (SNSCC) remain poorly understood due to its rarity. A subset of SNSCC is associated with human papillomavirus (HPV), but it is unclear whether HPV drives tumorigenesis or acts as a neutral bystander. Here, we show that HPV-associated SNSCC shares mutational patterns found in HPV-associated cervical and head and neck squamous cell carcinoma, including lack of TP53 mutations, hotspot mutations in PI3K and FGFR3 , enrichment of APOBEC mutagenesis, viral integration at known hotspots, and frequent epigenetic regulator alterations. We identify HPV-associated SNSCC-specific recurrent mutations in KMT2C , UBXN11 , AP3S1 , MT-ND4 , and MT-ND5 , with KMT2D and FGFR3 mutations correlating with reduced overall survival. We establish an HPV-associated SNSCC cell line, showing that combinatorial small-molecule inhibition of YAP/TAZ and PI3K synergistically suppresses clonogenicity. Combining YAP/TAZ blockade with vertical PI3K inhibition may benefit HPV-associated SNSCC, whereas targeting MYC and horizontal inhibition of RAS/PI3K may suit HPV-independent SNSCC.

Background: As the surgical repertoire for the management of sinonasal tumors evolves over time, an improved understanding of risks for postoperative complications is imperative. Objectives: To identify factors associated with 30-day postoperative complications following the resection of sinonasal tumors. Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried from 2005 to 2020 for patients undergoing open or endoscopic surgical resection of sinonasal tumors. A Cox proportional hazards model was used to identify factors associated with postoperative complications. Kaplan–Meier survival analyses and log-rank tests were used to compare time to complication onset. Frailty was defined as a 5-factor modified frailty index score > 2. Results: Of the 859 patients with sinonasal tumors, 539 (62.7%) were male, and the average age (± SD) was 59.3 ± 14.1 years. Postoperative complications were observed in 251 (29.2%) patients. The most common 30-day complications were bleeding requiring transfusions (n = 172; 20.0%) and ventilation longer than 48 h (n = 37; 4.3%). Frailty (aHR [95% CI]: 3.58 [1.80–7.12]), malignancy (3.43 [1.59–7.38]), and maxillary tumor location (2.40 [1.86–3.09]) were associated with greater risk for 30-day postoperative complications. Similarly, patients with frailty (χ² = 7.0; p = 0.008), malignant tumors (χ² = 13.4; p < 0.001), or maxillary sinus tumors (χ² = 34.6; p < 0.001) experienced earlier onset of postoperative complications. Conclusions: Frailty, malignancy status, and tumor location may modulate risk for 30-day postoperative complications following the resection of sinonasal tumors. These results may help to inform preoperative patient counseling and identify individuals at increased risk of postoperative complications.

On June 4, 1910, Harvey Cushing and Oskar Hirsch, separated by both surgical specialty and the Atlantic, independently performed their groundbreaking transsphenoidal operations that would shape the future of skull base surgery.[1] Together, their innovative approaches to the pituitary gland established the foundation of modern-day endoscopic skull base surgery. To recognize their legacy 115 years later, we propose that June 4 now become the annual International Skull Base Surgery Day. Surgery of the pituitary gland began in the late 1890s with transcranial approaches by the neurosurgical pioneer Sir Victor Horsley and others. However, with mortality rates as high as 80% and substantial perioperative morbidity, surgeons continued to explore alternative techniques.[2] [3] Herman Schloffer, an Austrian surgeon, had studied the cadaveric dissections of Italian surgeon, Davide Giordano, and in 1907, Schloffer performed the first transsphenoidal pituitary surgery with a disfiguring lateral rhinotomy, total nasal translocation, and open sphenoethmoidectomy. In 1909, Harvey Cushing modified the nasal translocation to remove a pituitary tumor for an acromegalic patient referred to him by Charles Mayo.[1] [4] Oskar Hirsch, a Czechoslovakian, who immigrated to Austria for medical school, became an otolaryngologist and studied endonasal sinus surgery with Markus Hajek in Vienna.[5] In March 1910, Hirsch successfully performed the first two-stage endonasal transsphenoidal resection of a pituitary tumor, after over a year of presenting and discussing the proposed technique.[6] Concerned that a two-staged procedure could result in an unacceptable delay of urgent optic nerve decompression, he refined his approach, and on June 4, 1910, Hirsch performed his first single-stage endonasal transsphenoidal pituitary tumor resection.[1] Hirsch would subsequently perform nearly 400 similar pituitary operations in Vienna, with significantly improved outcomes. As a Jewish surgeon, Hirsch was then forced to flee Austria by Nazi decree. He ultimately found refuge in Boston, which he chose in part due to earlier correspondence with Harvey Cushing who had once lived there as well.[7] In Boston, Hirsch would continue his innovative technique in collaboration with Massachusetts General Hospital neurosurgeon Hannibal Hamlin, the namesake and great-grandson of Abraham Lincoln's Vice President.[8] [9] Meanwhile, in Baltimore, Harvey Cushing, a pioneer of immeasurable impact in neurosurgery, was likewise dissatisfied with the morbidity of even his modified nasal translocation approach. By combining the concepts of his influences and collaborators, Cushing incorporated sublabial, inferior nasal, and submucosal septal approaches. On June 4, 1910, Cushing performed his first sublabial submucosal transseptal transsphenoidal pituitary tumor resection.[1] Cushing would further refine this technique, still used by neurosurgeons around the world today, for sublabial pituitary surgery and vastly improve his surgical outcomes. However, with his increasing mastery of cranial surgery and lack of modern visualization tools, he ultimately abandoned the transsphenoidal approach by 1929 and performed transcranial pituitary surgery for the remainder of his career.[10] Together, Harvey Cushing and Oskar Hirsch's work represented a pivotal departure from the more disfiguring, invasive, and dangerous approaches of the era. For patients with pituitary tumors, the rate of major complications dropped precipitously, and the contemporary understanding of cranial base surgery was born. The serendipitous timing of these operations, performed an ocean apart, underscores not only the convergence of neurosurgical and otolaryngological contributions to advancing skull base surgery since its inception but also the worldwide collaboration integral to the field's global development. Cushing and Hirsch, through their visionary and seminal work, have influenced generations of surgeons and impacted countless patients. Recognizing June 4 as International Skull Base Surgery Day would honor these luminaries and successive advancements, celebrate the multidisciplinary and international nature of our field, and inspire continued collaboration and innovation in skull base surgery. Article published online: 26 March 2025 © 2025. Thieme. All rights reserved. ARS-AAOA, LLC. The article has been co-published with permission in Journal of Neurological Surgery Part B and International Forum of Allergy & Rhinology. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany