Objectives:We evaluated the impact of teprotumumab therapy (TT) introduction on orbital decompression (OD) utilization for thyroid eye disease (TED) and compared rates of significant exophthalmos reduction (SER) and diplopia between TT and OD. Methods:Newly diagnosed TED patients treated pre (2015-2020) and post teprotumumab (2020-2025) FDA approval were identified from the EHR. Utilization trends, diplopia rates, and immediate (≤ 6 weeks post-intervention) and long-term follow-up SER (≥ 2 mm reduction) were studied. Results:Of 406 TED patients, 53 (36.8%) underwent OD in the pre-TT cohort (n = 144). Post-teprotumumab approval (n = 262), primary OD was performed in 29 (11.1%), of which 3 (10.3%) were subsequently placed on TT; primary TT was used in 68/262 (25.9%) with subsequent OD performed in 9 (13.2%). The remaining patients used other treatments (corticosteroids, orbital radiation, rituximab, tocilizumab, etc.). In the overall cohort, immediate SER was achieved in 94.4% of OD versus 83.8% of TT patients (p = 0.028), with greater median reduction in the OD group (5 vs. 4 mm; p = 0.001). At long-term follow-up (median 13 vs. 12 months), SER was sustained in 85.4% of OD and 62.9% of TT patients (p = 0.042). Pre-therapy diplopia was more prevalent in TT vs. OD patients (79.4% vs. 59.7%; p = 0.019). New-onset posttreatment diplopia was higher in the OD group (20.7% vs. 5.9%; p = 0.008). Conclusions:Rates of OD surgery declined following FDA approval of teprotumumab. OD achieved sustained and greater exophthalmos reduction but carried a higher risk of diplopia. Contemporaneous OD indications may have evolved to use in TT-recalcitrant TED or those in need of urgent decompression. Level of Evidence:4.

In cases where an expanded cholesteatoma has extensively eroded the petroclival bones, marsupialization of the cholesteatoma cavity without matrix removal through an endoscopic transsphenoidal approach is a feasible and safe option. This approach avoids CSF rhinorrhea and injury to critical structures which may be underlying and adherent to the cholesteatoma matrix, and periodic debridements address the disease satisfactorily.

Non-allergic rhinitis is a frequent yet underdiagnosed cause of chronic nasal symptoms, including nasal congestion, rhinorrhoea, and upper airway hyperreactivity. Its pathophysiology involves neurogenic dysregulation, leading to excessive mucus production and vasodilation. While medical therapy remains first-line, some patients experience persistent symptoms requiring surgical intervention. This review outlines key surgical options for refractory non-allergic rhinitis: inferior turbinate (IT) reduction, vidian neurectomy, and posterior nasal nerve (PNN) ablation. IT reduction-performed using cold instruments, radiofrequency, laser, coblation, or microdebrider-remains the cornerstone treatment for nasal obstruction, offering durable symptom relief with low complication rates. Vidian neurectomy effectively reduces rhinorrhoea but carries risks of ocular dryness and transient facial numbness, limiting its indication to severe, refractory cases. PNN interventions, including cryotherapy, cold-instrument techniques, and radiofrequency, provide a minimally invasive, outpatient alternative that selectively targets nasal parasympathetic and sensory fibers while sparing lacrimal innervation, yielding significant and lasting symptom improvement. Surgical management of non-allergic rhinitis is effective and safe when tailored to symptom profile, anatomy, and prior medical treatment response. Advances in endoscopic and minimally invasive approaches have reduced complications, establishing these procedures as integral options in comprehensive non-allergic rhinitis care.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5-67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8-53.3%) and 39.6% (95% CI: 32.5-46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1-3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p's < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42-5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25-7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

OBJECTIVE:Surgical repair and 3D-printed customized septal prosthesis (3D-PCSP) are options for septal perforation treatment. We performed a study to compare the clinical outcomes of surgery and 3D-PCSP using the NOSE-Perf Scale (NPfS). METHODS:A chart review was performed on patients undergoing surgical repair or 3D-PCSP placement between January 2018 and July 2024. The change in NPfS was used as primary endpoint. Demographics, ASA score, perforation size, etiology, and follow-up duration were reported. RESULTS:Thirty-five patients, 23 for surgical repairs and 12 for 3D-PCSP, were included in this review [median (IQR)]. In the surgical repair group, perforation length and height measured 12 (10-18) mm and 10 (8-15) mm, respectively. Baseline NPfS was 24 (16-32), and this decreased to 8 (6-13) following surgical repair (p < 0.001). Follow-up time was 12 (5-21) months. In the 3D-PCSP group, septal perforation length and height measured 25 (15-30) mm and 17 (15-20) mm, respectively. The baseline NPfS was 17 (3-24.5), and this decreased to 9.5 (7-13) following 3D-PCSP placement (p = 0.001). The follow-up was 18.4 (16-23) months. NPfS reduction was greater for surgical repair (p = 0.018). CONCLUSIONS:Surgery and 3D-PCSP offer meaningful symptom relief for NSP patients. Treatment decisions should be individualized through shared decision-making that considers patient comorbidities, preferences, surgeon experience, and risk tolerance. In this cohort, surgical repair was associated with greater NPfS reduction compared with 3D-PCSP placement. LEVEL OF EVIDENCE: 3:

ABSTRACT Objective Odontogenic sinusitis (ODS) ranges from isolated maxillary disease to pansinusitis. We compared patient characteristics, microbial and histopathological features, and symptom outcomes following endoscopic sinus surgery (ESS) between low and high radiographic burden ODS patients. Methods ODS patients undergoing ESS between 01/2013 and 08/2024 were reviewed. Preoperative CT scans were used to classify patients into high radiographic burden [with ostiomeatal complex (OMC) opacification] and low radiographic burden ODS [clear OMC]. Demographic, microbiological, and histopathological data were analyzed. Symptom improvement was assessed using pre‐ and post‐operative SNOT‐22 scores. Results Eighty‐seven patients were identified (high CT burden: 70; low CT burden: 17). High CT burden ODS was associated with older age (p = 0.014), higher overall degree of inflammation (p = 0.002), hyperplastic/papillary epithelial changes (p = 0.034), and neutrophil infiltration (p = 0.003). Culture of classic ODS bacteria (Fusobacterium spp., Prevotella spp., mixed anaerobes, Streptococcus anginosus group) did not correlate with CT disease burden (p = 0.110). No independent predictors of radiographic high‐burden disease were identified. Post‐ESS, significant reduction in total and rhinologic SNOT‐22 scores was only observed in the radiographic high‐burden ODS group (n = 39; median reductions: 23 and 12 respectively; p < 0.001). Conclusion High radiographic burden was associated with older patients and with tissue inflammation level. Classic ODS bacterial profile did not associate with increased CT burden. While these findings remain exploratory, the observed differences in inflammatory and symptomatic profiles between groups suggest that radiographic burden warrants further study as a potential factor in ODS clinical decision‐making. Level of Evidence 3.

BackgroundMepolizumab blocks IL-5, targeting eosinophilic type-2 inflammation. Due to existing phenotype driven patient selection, evidence of its effectiveness in primary diffuse CRS and CRS without nasal polyps (CRSsNP) and in real-world populations is limited. Our objective was to evaluate the real-world effectiveness of mepolizumab in patients with primary diffuse CRS, regardless of nasal polyp status, and to assess outcomes across CRS phenotypes and prior surgical history.MethodsAdults with primary diffuse CRS treated with mepolizumab for ≥6 months were identified. Pre- and post-therapy outcomes included serum eosinophil counts, Lund-Mackay CT scores, Lund-Kennedy endoscopic scores, and SNOT-22 symptom scores. Subgroup analyses were performed by CRS phenotype (CRSwNP vs. CRSsNP) and prior endoscopic sinus surgery (ESS). Biologic switching and discontinuation were recorded.ResultsAmong 277 patients (mean age 60.8 ± 14.7 years; 54.9% female), 93.5% had type-2 comorbidities, 29.6% had CRSsNP, and 27.8% were ESS-naïve. The median duration of mepolizumab therapy was 31 months. Mepolizumab therapy significantly reduced serum eosinophils (median 0.57 to 0.07 ×109/L, p<0.001) and Lund-Mackay scores (median 14 to 10, p<0.001), which was consistent across all subgroups. Improvements in SNOT-22 and endoscopic scores were modest and not consistently significant. CRSwNP patients were more likely to undergo ESS during therapy, but time to first post-therapy ESS was longer than in CRSsNP. There were no differences in likelihood of undergoing ESS during therapy, time to subsequent ESS, or oral corticosteroid use between prior ESS and ESS-naïve patients. Biologic switching occurred in 24.9%, and discontinuation in 16.6%, primarily due to disease recalcitrance.ConclusionMepolizumab effectively reduced systemic eosinophilia and radiographic disease burden in primary diffuse CRS, independent of phenotype or prior ESS. Symptom improvement was variable, highlighting the heterogeneity of clinical response. These findings support an endotype-driven approach to biologic therapy and suggest that IL-5 blockade may benefit selected CRSsNP patients.

Inverted sinonasal papilloma (ISP) and respiratory epithelial adenomatoid hamartoma (REAH) are sinonasal lesions with overlapping clinical, radiographic, and histologic features, making accurate diagnosis challenging. ISP is a benign but aggressive tumor with a propensity for local destruction, recurrence, and malignant transformation, whereas REAH is a hamartomatous lesion often arising in the olfactory cleft. We present four patients with lesions initially suspected to be ISP based on intraoperative frozen section but ultimately diagnosed as REAH on permanent pathology. All patients had polypoid sinonasal masses, frequently involving or adjacent to the olfactory cleft. Intraoperative frozen sections were often inconclusive or favored ISP, reflecting the difficulty of distinguishing these entities. Histologic analysis revealed that epithelial thickness served as a key morphologic feature differentiating ISP from REAH, with REAH exhibiting ciliated glandular proliferation and ISP characterized by hyperplastic epithelium with features of columnar and squamous differentiation. These patients underscore the diagnostic pitfalls of small biopsies and frozen sections, and highlight the importance of permanent specimens and collaboration with experienced pathologists. Accurate differentiation is critical, as management strategies differ substantially: ISP requires aggressive resection and long-term surveillance, while REAH may be treated with limited excision and minimal follow-up.

ABSTRACT Objectives To review septal perforation management and outcomes in patients with hereditary hemorrhagic telangiectasia (HHT). Methods Collection and presentation of patient demographic, perforation size, and prior perforation and HHT treatment data over a 20‐year period. Symptom and quality of life treatment outcomes were determined using the Nasal Obstruction Symptom Evaluation (NOSE)‐Perf scale and the 5‐Factor Glasgow Inventory (GBI‐5F), respectively, in patients treated since 2017. Results Nine patients met study criteria. Mean (range) age was 64.4 (52–80) years and seven were biological males. Mean (range) perforation length and height were 1.9 (1.2–2.6) and 1.4 (1.0–1.8) cm. Four patients were treated with a customized septal button, one with posterior septal resection, and four with endonasal bilateral mucosal flap repair supported with an interposition graft. The button prostheses were well tolerated and the surgical closures successful at 8–60 months postoperatively. Subjective responses in the first three patients, and NOSE‐Perf with GBI‐5F scores in the latter six patients, demonstrated symptom and quality of life improvement for all patients. Perforation repair patients demonstrated substantial improvement in mean GBI‐5F subdomain scores for quality of life, self‐confidence, and social involvement and all have undergone sodium tetradecyl sclerotherapy injection postoperatively without re‐perforation. Conclusion Symptom and quality of life improvement can be achieved in HHT patients with a perforation using customized septal buttons, posterior septal resection, or bilateral flap surgical repair. Surgical closure combined with injection sclerotherapy is feasible with a low risk of re‐perforation and represents an effective treatment strategy in selected patients. Level of Evidence 4.

PURPOSE OF REVIEW:Increasing evidence suggests that epigenetic regulation plays a central role in chronic rhinosinusitis pathogenesis, heterogeneity, and treatment response. This review summarizes current knowledge of epigenetics in CRS pathogenesis, their role in endotype differentiation, and potential as diagnostic and therapeutic targets. RECENT FINDINGS:Distinct epigenetic signatures have been identified across CRS subtypes. Hypermethylation of TSLP and differential regulation of FZD5, IL8, and EMT-related genes distinguish eosinophilic CRSwNP from other phenotypes. Specific microRNAs (miR-941, miR-21, miR-125b, miR-155) correlate with disease severity, tissue eosinophilia, and corticosteroid responsiveness, highlighting their utility as noninvasive biomarkers. Experimental data suggest that targeting DNMTs or HDACs may reverse pathogenic remodeling. Emerging therapeutic approaches - such as biologics modulating epigenetically controlled cytokines (e.g. tezepelumab) and engineered extracellular vesicle-based miRNA delivery - illustrate translational promise. SUMMARY:Epigenetic mechanisms critically influence CRS pathogenesis and clinical variability. Their modulation offers novel opportunities for biomarker discovery, disease stratification, and personalized therapy. Future research should focus on standardizing epigenetic profiling methodologies, validating candidate biomarkers in diverse populations, and integrating multiomics and single-cell approaches to uncover cell-specific regulatory networks. These advances may enable precision medicine in CRS, bridging the gap between molecular mechanisms and targeted clinical management.

Objectives/hypothesisChronic rhinosinusitis (CRS) may be triggered by environmental insults. We hypothesized that CRS results from epigenetic modifications of host DNA from external insults, leading to downstream RNA/DNA gene expression changes and immuno-mechanical disruptions. We therefore performed a multi-omics study integrating epigenetic (DNA methylation), transcriptomic (mRNA), and proteomic (cytokine) data of CRS sinonasal tissue to visualize interactions amongst these modalities to study our hypothesis.MethodsSinonasal tissue was collected from 14 prospectively enrolled CRS and control subjects. Cytokine, mRNA transcriptome, and DNA methylome analysis were performed. Multi-omics analysis via joint dimensional reduction (JDR) was conducted.ResultsMulti-omics unsupervised clustering separated subjects into two distinct groups: one cluster of 9 CRS subjects and another with 3 controls and 2 non-eosinophilic CRSsNP subjects. DNA methylation, followed by mRNA expression, contributed most to cluster assignment. DNA methylation was the most significant data modality contributing to total variance on JDR. Cytokines critical in CRS (IL-5, IL-13, IL-10, IFNγ, IL-6) associated with hundreds of differentially methylated regions (DMRs) and mRNA. On conjoint analyses, common upstream DMRs and mRNAs were linked to cytokines IL-5 and IL-13, cytokines IL-10 and IFNγ, and cytokines IFNγ and IL-6, respectively.ConclusionsOur results support the hypothesis that environmental insults may be significant drivers of CRS pathogenesis through epigenetic mechanisms that result in dysregulated mRNA transcription and cytokine expression. The most novel part of this study is our multi-omics approach that used integration of epigenetic (DNA methylation), transcriptomic (mRNA), and proteomic (cytokine) data to uncover insights into CRS pathogenesis; this is the first of its kind in CRS etiopathogenesis. The multi-omics analysis clearly separated clusters of control and CRS subjects, demonstrating its validity in future research. The study also identified interactions of methylated DNA, mRNA, and cytokines in CRS pathogenesis, highlighting novel molecules and pathways that may be potential therapeutic targets.

Background/AimEosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease associated with nasal polyposis. Multiple biologics are used for managing EGPA, including some approved for nasal polyps (NP). This study investigated real-world biologic prescription patterns for EGPA and their impact on NP and endoscopic sinus surgery (ESS) use.MethodsEGPA patients with NP treated with a biologic at any Mayo Clinic site (January 2010 to January 2024) were identified by querying the unified electronic medical record. Patterns of biologic therapy, clinical course, impact on NP, and performance of ESS were studied.ResultsEighty patients were identified. Overall, 71 of 80 (88.75%) patients underwent ESS, with 62 of 80 (77.5%) undergoing 131 ESS procedures prior to biologic therapy. ESS for recalcitrant NP (47 episodes) was performed on 38 of 80 (47.5%) patients on biologics. Biologic monotherapy was used in 90% (72) of patients; mepolizumab (81.9%) was the most common, followed by rituximab (23.6%), benralizumab (18.1%), and dupilumab (12.5%). Switching of biologics was observed in 28 of 80 patients. Concurrent dual-biologic therapy was used in eight (10%) patients. For patients on single-agent biologic therapy, ESS was performed on 52.5% of patients on mepolizumab, 23.5% on rituximab, 42.8% on benralizumab, and 22.2% on dupilumab.ConclusionsMultidisciplinary multi-modality treatment with biologics and ESS appeared to be the mainstay of controlling NP in EGPA. Mepolizumab was the most frequently used biologic. Dual biologic therapy was necessary in 10% of patients. Overall, 71 of 80 (88.75%) patients had ESS, with almost half the study population (47.5%) undergoing ESS after initiating biologic treatment.

Background/Objectives: Although endoscopic dacryocystorhinostomy (DCR) has been widely accepted as the procedure of choice for nasolacrimal duct obstruction (NLDO) management due to most etiologies, concerns regarding the reactivation of disease and involvement of surrounding structures add to hesitation in its utilization for granulomatosis with polyangiitis (GPA) patients. No study has directly compared outcomes of external vs. endoscopic DCR in GPA patients. This information can be helpful for patient counselling and choosing a personalized surgical approach for the best results. Methods: A scoping review of the literature was performed in January 2024. The following databases were searched using a combination of MeSH (Medical Subject Headings) and keywords: Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science. This scoping review is not registered. Medical records of two GPA patients who underwent endoscopic DCR at our center were reviewed. Results: The search yielded 96 articles; 15 articles met the inclusion criteria for a full review. Six studies with 22 procedures reported 100% success with endoscopic DCR. Nine studies with 122 procedures reported success in 88.5% of cases with external DCRs. Additional perioperative immunosuppression was recommended in patients with severe mucosal inflammation. The case series presents the disease course, details of surgery, and perioperative management in two GPA patients with NLDO who underwent endoscopic DCR successfully. Conclusions: Endoscopic DCR was associated with equivalent or better success rates and lower complications compared to external DCR in GPA patients. Ensuring disease remission state and appropriate immunomodulatory therapy can help prevent the proposed risk of endonasal disease reactivation with endoscopic DCR.

KEY POINTS:Contemporary aspirin exacerbated respiratory disorder (AERD) therapy commonly includes aspirin desensitization (55%) and biologics (48%). Aspirin desensitization therapy has higher discontinuation rates than biologics. Patients receiving biologics are younger, and ∼25% of the patients switch to other agents.

Balloon-assisted dilation (BAD) of paranasal sinus ostia is a Food and Drug Administration (FDA)-approved minimally-invasive procedure used to treat medically refractory chronic rhinosinusitis. Several large cohort studies have reported relatively-low complication rates with BAD. Thus, users of this technology may perceive this to be a safer alternative to formal dissection of the frontal and sphenoid sinus and perform these as office-based procedures. Here, we present 2 patients who underwent BAD of the sphenoid sinus and developed cerebrospinal fluid leak (CSF) leaks with pneumocephalus. Both patients had thinning of the planum sphenoidale in generously-pneumatized sphenoid sinuses. Although BAD is considered safe, review of the current literature demonstrates that serious complications can occur. These case reports demonstrate the potential for skull base injury, particularly in hyper-pneumatized sphenoid sinuses with dehiscent bone. Preoperative anatomic evaluation is crucial to identify at-risk patients. During BAD, trauma to critical structures may cause CSF leak and result in pneumocephalus. This knowledge is important for improving surgical decision-making and patient counseling.Level of Evidence: III.

Objectives:Transnasal endoscopic sphenopalatine artery ligation (TESPAL) has been proposed as a first-line therapy for intractable epistaxis before utilizing posterior nasal packing and embolization. A specific procedure code for TESPAL was newly introduced in 2018, adding to two prior codes for procedural control of epistaxis. This study compares all-time utilization of the TESPAL CPT code in Medicare beneficiaries with alternative procedural codes for epistaxis management. Methods:The publicly available data from the Centers for Medicare and Medicaid Services in the 2013-2022 period was analyzed for the reporting of TESPAL (31241), transcatheter permanent occlusion or embolization of noncentral nervous system, head, or neck (61626), and endoscopic control of epistaxis (31238) codes. Welch two sample t-test and linear regression were used to characterize CPT code utilization. Results:From 2018 to 2022, TESPAL CPT code reporting averaged 378 instances annually, with a stable utilization trend (p = 0.432). CPT codes 61626 and 31238 averaged 1429 and 3779 instances annually, respectively. CPT 31238 showed a significant decline (p < 0.001), and CPT 61626 showed a stable trend (p = 0.082). There was a significant decline in CPT code 31238 use after 2018 (p < 0.01). CPT 61626 showed a significant increase in usage post-2018 (t = 2.90, p = 0.044). Conclusion:After an initial increase in 2019, TESPAL reporting flattened, while CPT 61626 (which includes all embolization in head and neck vessels) significantly increased post-2018. As recent studies show significant advantages of TESPAL over embolization, these findings warrant further attention and study. Level of Evidence:3.

ABSTRACT Objectives Saddle nose deformity (SND) can be associated with nasal septal perforation (NSP). Both SND and NSP are observed in granulomatosis with polyangiitis (GPA) patients. This study aimed to compare the prevalence and severity of SND in GPA vs. non‐GPA patients with NSP. Methodology NSP patients who visited tertiary rhinology or facial plastic surgery clinics from January 2010 through December 2023 were grouped into GPA and non‐GPA cohorts. The area of NSP, SND incidence, and SND severity (Daniel and Brenner's classification) were compared between the cohorts. Results Of 168 patients identified with NSP, 18 had GPA and 150 had non‐GPA diagnoses. Twelve GPA patients and 10 non‐GPA patients had SND. The odds ratio for SND association in GPA patients with NSP vs. non‐GPA patients was 31.3 (95% CI: 9.5–102.9), and 19.4 (95% CI: 4.3–87.7) after controlling for the NSP area. GPA patients with SND had a larger NSP area (median 670 mm 2 , IQR: 315.5–1061.3) compared to non‐GPA patients with SND (175.3 mm 2 , 113.1–204.1; p < 0.001). The severity of SND was similar between GPA and the non‐GPA group ( p = 0.09). The area of NSP did not predict the severity of SND ( p = 0.17). Conclusion GPA diagnosis was associated with larger NSPs and a higher risk of SND compared to non‐GPA etiologies; however, the severity of saddling did not differ between GPA and non‐GPA etiologies. GPA is an independent risk factor associated with SND irrespective of the size of septal perforation. The NSP area did not predict the severity of SND. Level of Evidence: 4.