Immunological memory diversity in the human upper airway.

The upper airway is an important site of infection, but immune memory in the human upper airway is poorly understood, with implications for COVID-19 and many other human diseases1-4. Here we demonstrate that nasal and nasopharyngeal swabs can be used to obtain insights into these challenging problems, and define distinct immune cell populations, including antigen-specific memory B cells and T cells, in two adjacent anatomical sites in the upper airway. Upper airway immune cell populations seemed stable over time in healthy adults undergoing monthly swabs for more than 1 year, and prominent tissue resident memory T (TRM) cell and B (BRM) cell populations were defined. Unexpectedly, germinal centre cells were identified consistently in many nasopharyngeal swabs. In subjects with SARS-CoV-2 breakthrough infections, local virus-specific BRM cells, plasma cells and germinal centre B cells were identified, with evidence of local priming and an enrichment of IgA+ memory B cells in upper airway compartments compared with blood. Local plasma cell populations were identified with transcriptional profiles of longevity. Local virus-specific memory CD4+ TRM cells and CD8+ TRM cells were identified, with diverse additional virus-specific T cells. Age-dependent upper airway immunological shifts were observed. These findings provide new understanding of immune memory at a principal mucosal barrier tissue in humans.

Lower serum 15-HETE level predicts nasal ILC2 accumulation during COX-1 inhibition in AERD.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D2, and low levels of prostaglandin E2. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown. OBJECTIVE: We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD. METHODS: Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis. RESULTS: Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081). CONCLUSION: Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.

Development of parallel forms of a brief smell identification test useful for longitudinal testing.

Although there are numerous brief odor identification tests available for quantifying the ability to smell, none are available in multiple parallel forms that can be longitudinally administered without potential confounding from knowledge of prior test items. Moreover, empirical algorithms for establishing optimal test lengths have not been generally applied. In this study, we employed and compared eight machine learning algorithms to develop a set of four brief parallel smell tests employing items from the University of Pennsylvania Smell Identification Test that optimally differentiated 100 COVID-19 patients from 132 healthy controls. Among the algorithms, linear discriminant analysis (LDA) achieved the best overall performance. The minimum number of odorant test items needed to differentiate smell loss accurately was identified as eight. We validated the sensitivity of the four developed tests, whose means and variances did not differ from one another (Bradley-Blackwood test), by sequential testing an independent group of 32 subjects that included persons with smell dysfunction not due to COVID-19. These eight-item tests clearly differentiated the olfactory compromised subjects from normosmics, with areas under the ROC curve ranging from 0.79 to 0.83. Each test was correlated with the overall UPSIT scores from which they were derived. These brief smell tests can be used separately or sequentially over multiple days in a variety of contexts where longitudinal olfactory testing is needed.

Innate immune cell dysregulation drives inflammation and disease in aspirin-exacerbated respiratory disease.

Aspirin-exacerbated respiratory disease (AERD) is a complex inflammatory disorder that is not generally viewed as a disease involving the adaptive immune system but instead one largely driven by the innate immune system. This article focuses on the cellular dysregulation involving 4 central cell types: eosinophils, basophils, mast cells, and innate lymphoid type 2 cells. AERD can be envisioned as involving a self-perpetuating vicious circle in which mediators produced by a differentiated activated epithelial layer, such as IL-25, IL-33, and thymic stromal lymphopoietin, engage and activate each of these innate immune cells. The activation of these innate immune cells with their production of additional cytokine/chemokine and lipid mediators leads to further recruitment and activation of these innate immune cells. More importantly, numerous mediators produced by these innate immune cells provoke the epithelium to induce further inflammation. This self-perpetuating cycle of inflammation partially explains both current interventions suggested to ameliorate AERD (eg, aspirin desensitization, leukotriene modifiers, anti-IL-5/IL-5 receptor, anti-IL-4 receptor, and anti-IgE) and invites exploration of novel targets as specific therapies for this condition (prostaglandin D2 antagonists or cytokine antagonists [IL-25, IL-33, thymic stromal lymphopoietin]). Several of these interventions currently show promise in small retrospective analyses but now require definite clinical trials.

Double-unit unrelated cord blood transplantation for thalassemia major: Comparison with HLA-identical sibling bone marrow transplantation.

UCBT recipients with TM are at high risk of EF related to low number of stem cells and prior alloimmunization after multiple blood transfusions. Here, we evaluated the safety and efficacy of double-unit UCBT using TT-containing conditioning regimens in TM. Retrospective analysis of children who underwent double-unit UCBT for TM in the Prince of Wales Hospital between August 2007 and January 2017, and outcome of double-unit UCBT for TM was compared with outcome of HLA-matched sibling BMT. Ten patients, median age 4.2 years, received double-unit UCBT. All patients except one engrafted at a median of 19 days. None of the patients with successful engraftment had grade III or IV aGVHD. Among nine patients with successful engraftment, six of nine patients evaluable after day 100 developed cGVHD. All patients with cGVHD were well controlled after treatment with steroids and/or supportive care and maintained good quality of life. In comparison with patients receiving BMT, those given UCBT had slower platelet recovery, and more cGVHD. With a median follow-up of 272 months after BMT and 84 months after UCBT, the 8-year OS after BMT and UCBT was 92% and 90% (P = .84), whereas 8-year DFS after BMT and UCBT was 87% and 80% (P = .54). UCB could be an acceptable source of stem cells for transplantation of TM patients when HLA-matched family bone marrow donors are NA.

Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling.

Coordination of neural crest cell (NCC) induction and delamination is orchestrated by several transcription factors. Among these, Sry-related HMG box-9 (Sox9) and Snail2 have been implicated in both the induction of NCC identity and, together with phoshorylation, NCC delamination. How phosphorylation effects this function has not been clear. Here we show, in the developing chick neural tube, that phosphorylation of Sox9 on S64 and S181 facilitates its SUMOylation, and the phosphorylated forms of Sox9 are essential for trunk neural crest delamination. Both phosphorylation and to a lesser extent SUMOylation, of Sox9 are required to cooperate with Snail2 to promote delamination. Moreover, bone morphogenetic protein and canonical Wnt signaling induce phosphorylation of Sox9, thereby connecting extracellular signals with the delamination of NCCs. Together the data suggest a model in which extracellular signals initiate phosphorylation of Sox9 and its cooperation with Snail2 to induce NCC delamination.

A Consistent Endoscopic Landmark to Identify the Anterior Ethmoidal Artery.

OBJECTIVE: The anterior ethmoidal artery (AEA) is an important structure to identify during endoscopic sinus surgery. Although identification on imaging is easily taught, a consistent endoscopic landmark for the AEA, independent of anatomic ethmoid cell variation, is lacking, leaving many surgeons unclear about the exact location without dependence on navigation. Here, we describe a consistent endoscopic landmark, regardless of anatomical ethmoid variation. METHODS: We prospectively enrolled adult patients undergoing endoscopic surgery involving frontal and ethmoid sinuses in this observational study. The AEA landmark was defined simply as the septation or ridge one step back along the ethmoid skull base from the posterior table of the frontal sinus. The gold standard to calculate the sensitivity of our endoscopic landmark was an image-navigation system, registered to within 1.5 mm accuracy, locating the AEA within three planes. Both endoscopic and computerized tomography (CT) images of the pointer at the landmark were taken simultaneously. The concordance of endoscopic to navigation images was independently assessed by three blinded rhinologists. RESULTS: Forty patients were included in our study with 73 sides analyzed. Diagnoses included chronic rhinosinusitis without polyps (52.5%), with polyps (22.5%), recurrent acute sinusitis (15%), sinonasal tumors (7.5%), and odontogenic sinusitis (2.5%). The AEA was accurately identified using our endoscopic landmark in 97.3% of the cases (71/73). Of the two cases in which the AEA was not found within the landmark, the artery was located ≤1 mm posteriorly. CONCLUSION: We describe a consistent endoscopic landmark to identify the AEA, conserved across various clinical diagnoses and anatomic variations in sinus structure. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1096-1099, 2024.

Pro-inflammatory markers associated with COVID-19-related persistent olfactory dysfunction.

INTRODUCTION: While localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID-19) olfactory dysfunction (OD), persistent COVID-19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling. METHODS: COVID-19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID-19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti-viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann-Whitney tests with multi-comparison adjustment. Viral RNA was assessed through RT-PCR using the COVID-19 N2 primer. RESULTS: Thirty-five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non-COVID no OD). Significant differences in IFN-λ1 (p = 0.007) and IFN-γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN-α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN-γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non-COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts. CONCLUSION: IFN pathway cytokines were found elevated in the olfactory microenvironment of COVID-19 persistent OD compared to those with no OD and no prior history of COVID-19 infection.

Accessing the Eustachian tube: Conventional nasal spray vs. exhalation delivery system and the impact of targeted endoscopic sinus surgery on topical distribution patterns.

BACKGROUND: Eustachian tube dysfunction (ETD) may occur distinct from, or in conjunction with, chronic rhinosinusitis (CRS+ETD). Intranasal corticosteroid sprays are often prescribed for ETD, although ET distribution may be limited. To date, no anatomic studies compare nasopharynx (NP) distribution between conventional nasal sprays (NS) and exhalation delivery systems (EDS) after surgery. This study utilizes a cadaver model to examine topical NP delivery using EDS vs. NS before and after targeted endoscopic sinus surgery (ESS). METHODS: Sixteen sinonasal cavities were administered fluorescein solution via NS and EDS before and after maxillary antrostomy and anterior ethmoidectomy, followed by nasal endoscopy of the NP and ET orifice. Seven blinded experts submitted staining ratings of endoscopy images on a 0- to 3-point scale, with ratings averaged for analysis. RESULTS: Interrater reliability was excellent (intraclass correlation, 0.956). EDS was associated with significantly greater NP staining vs. NS in a pooled cohort of nonsurgical and ESS specimens (1.19 ± 0.81 vs. 0.78 ± 1.06; p = 0.043). Using a logistic regression model, EDS significantly outperformed NS in nonsurgical (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.21-10.09; p = 0.021) and post-ESS (OR, 9.00; 95% CI, 1.95-41.5; p = 0.005) specimens, with the greatest relative staining observed for EDS after targeted ESS (OR, 18.99; 95% CI, 3.44-104.85; p = 0.001). CONCLUSIONS: EDS is more effective than NS in topical delivery to the NP and ET orifices in cadavers. Targeted ESS may facilitate greater NP penetration by EDS compared with NS, with possible synergism after ESS for augmented delivery. These findings suggest a role for EDS delivery methods for ETD management and in CRS+ETD patients undergoing sinus surgery.

Delivering Therapy to the Olfactory Cleft: A Comparison of the Various Methods of Administering Topical Nasal Medications.

Background and objective Chronic rhinosinusitis (CRS) is an inflammatory condition affecting the nasal mucosa, and it causes olfactory dysfunction (OD) in up to 78.2% of patients. Corticosteroids are the mainstay of treatment to shrink nasal polyposis, reduce inflammation, and improve olfactory function. While many delivery methods for topical nasal corticosteroids exist, there is scarce data on the efficacy of the various medication delivery methods to the olfactory cleft (OC). In light of this, this study aimed to compare the following delivery methods to the OC: conventional nasal spray (NS), nasal drops in the Kaiteki position (KP), and exhalation delivery system (EDS). Methods We evaluated 16 sinonasal cavities from eight cadaver specimens in this study. Each sinonasal cavity was administered fluorescein dye solution via NS, KP, and EDS. Following administration, nasal endoscopy was employed to capture staining patterns in the OC. OC staining was rated with scores ranging from 0 (no staining) to 3 (heavy staining) after each administration of dye solution. Mean OC staining ratings were calculated and compared using the Kruskal-Wallis rank sum test and the Wilcoxon signed-rank test. Results The mean OC staining score for the different delivery methods was as follows - NS: 1.095 ± 1.008, EDS: 0.670 ± 0.674, and KP: 2.038 ± 1.097. Nasal drops in the KP had a significantly higher staining score compared to NS (p=0.041) and EDS (p=0.003). However, there was no significant difference in staining scores between NS and EDS. Conclusions Nasal drops in the KP are more effective at reaching the OC than NS or EDS and should be considered as a first-line modality for administering topical medications when treating OD.

Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial.

INTRODUCTION: The current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss. METHODS: This multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT] ≤ 33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale. RESULTS: A total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p = 0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported. CONCLUSION: Olfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy.

Lmx1a and lmx1b function cooperatively to regulate proliferation, specification, and differentiation of midbrain dopaminergic progenitors.

LIM homeodomain transcription factors, Lmx1a and Lmx1b, are required for the development of midbrain dopaminergic (mDA) neurons. Lmx1b is required for the specification and maintenance of mDA neurons, primarily due to its role in isthmic organizer development that is essential for the induction of mDA neurons. Here, we conditionally deleted Lmx1b in the ventral neural tube using ShhCre and found that Lmx1b conditional mutant mouse embryos show no defect in the development and maintenance of mDA neurons. In addition, Dreher (Lmx1a mutant) embryos display only a moderate reduction in the number of mDA neurons, suggesting that the related family member Lmx1b might compensate for Lmx1a function. We therefore generated Lmx1a and Lmx1b double mutants. Severe loss of mDA neurons occurred in Lmx1a(dr/dr);Shh(Cre/+);Lmx1b(f/f) double mutants due to essential roles for Lmx1a and Lmx1b in regulating the proliferation and neuronal commitment of mDA progenitors through the expression of Wnt1 and Ngn2, respectively. Lmx1a and Lmx1b also negatively regulate Hes1 expression and consequently cell cycle exit through activation of p27(Kip1) expression. In addition, Lmx1a and Lmx1b also regulate the expression of floor plate genes such as Corin and Slit2 and specification of postmitotic mDA neurons. These defects were more severe with decreasing gene dosage of Lmx1a and Lmx1b or observed only when all four copies of Lmx1a and Lmx1b genes were inactivated. Together, our results demonstrate that Lmx1a and Lmx1b function cooperatively to regulate proliferation, specification, and differentiation of mDA progenitors, including their floor plate-like properties.

Impact of COVID-19 versus chronic rhinosinusitis/rhinitis associated olfactory dysfunction on health utility and quality of life.

Background: Olfactory dysfunction (OD) is associated with both post-viral and inflammatory etiologies such as COVID-19 and chronic rhinosinusitis/rhinitis (CRS/R) respectively, to result in reduced quality of life (QoL). However, the former typically induces a sudden-onset OD while the latter has a gradual presentation. This study aims to establish and compare health utility values (HUVs) and olfactory-specific QoL measurements between patients with COVID-19 and CRS/R related OD. Methods: This prospective study surveyed COVID-19 and CRS/R patients with self-reported OD using HUV assessments (EuroQol-visual analog scale [EQ-VAS], EuroQol-5 dimension [EQ-5D], time trade-off [TTO]) and olfactory and sinonasal QoL measures (questionnaire of olfactory disorders -negative and positive statements [QOD-NS + PS] and sino-nasal outcome test [SNOT-22]). A subgroup of subjects completed objective olfactory testing. Intergroup mean scores were compared using Mann-Whitney U tests. Results: One hundred eleven subjects were enrolled: mean age ± SD (43.0 ± 15.4 years), 55.9% female. CRS/R was associated with lower HUVs as measured by EQ-VAS (CRS/R: 0.67 ± 0.18 vs. COVID-19: 0.74 ± 0.19, p = .03) and worse SNOT-22 scores in both overall (CRS/R: 49.03 ± 21.04 vs. COVID-19: 27.58 ± 18.45, p < .001) and subgroup analysis of objectively confirmed OD subjects (CRS/R: 52.40 ± 22.78 vs. COVID-19: 29.84 ± 21.10, p = .01). On the other hand, COVID-19 has greater burden on olfactory-specific QoL (QOD-NS + PS, COVID-19: 23.19 ± 13.73 vs. CRS/R: 17.25 ± 11.38, p = .04). Both groups demonstrated a similar decrease in health using the EQ-5D assessment. Conclusion: CRS/R associated OD has a more severe impact on general health and sinonasal specific QoL outcomes, while COVID-19 associated OD has a greater burden on olfactory-specific QoL. Level of evidence: Level 2c.

Clinical factors associated with lower health scores in COVID-19-related persistent olfactory dysfunction.

BACKGROUND: Patients with persistent COVID-19 olfactory dysfunction (OD) commonly report parosmia. Understanding the impact of COVID-19 OD and parosmia is critical to prioritizing research and interventions. In this study we investigate the impact of parosmia and other clinical and disease characteristics on health state utility values (HUVs) for those with persistent COVID-19 OD. METHODS: Patients with a history of COVID-19 diagnosis and persistent OD were recruited from a tertiary medical center and a social media support forum for chemosensory dysfunction. Clinical characteristics and disease-specific symptoms were obtained along with self-reported history of smell function and presence of parosmia. HUVs were calculated using indirect (EuroQol 5-Dimension [EQ-5D]) and direct (VAS) measures. RESULTS: Our study included 286 subjects (75.52% women) with persistent COVID-19-related OD. Results (mean ± standard deviation) of HUVs based on EQ-5D and VAS were 0.81 ± 0.14 and 0.73 ± 0.21, respectively. Mean self-reported smell function (on a 0-10 scale) was 9.67 ± 1.25 pre-COVID-19, 0.93 ± 2.34 at diagnosis, and 3.39 ± 2.32 at most current assessment. A total of 89.16% of the subjects reported parosmia and 24.13% sought medical care for anosmia. Seeing an MD for OD (p < 0.001), female gender (EQ-5D only, p = 0.002), a history of chronic pain (p < 0.05) and depression/anxiety (EQ-5D only, p < 0.001) predicted worse health. Parosmia and persistent symptoms, such as shortness of breath, were associated with lower EQ-5D and VAS scores, but did not independently predict poorer health scores on multivariable analysis. CONCLUSION: Persistent COVID-19 OD results in health states comparable to other chronic diseases.

Immunohistochemical and qPCR Detection of SARS-CoV-2 in the Human Middle Ear Versus the Nasal Cavity: Case Series.

Viral infections have already been implicated with otitis media and sudden sensorineural hearing loss. However, the pathophysiology of COVID-19 as it relates to otologic disorders is not well-defined. With the spread of SARS-CoV-2, it is important to evaluate its colonization of middle ear mucosa. Middle ear and nasal tissue samples for quantitative RT-PCR and histologic evaluations were obtained from post-mortem COVID-19 patients and non-diseased control patients. Here we present evidence that SARS-CoV-2 colonizes the middle ear epithelium and co-localizes with the primary viral receptor, angiotensin-converting enzyme 2 (ACE2). Both middle ear and nasal epithelial cells show relatively high expression of ACE2, required for SARS-CoV-2 entry. The epithelial cell adhesion molecule (EpCAM) was use as a biomarker of epithelia. Furthermore, we found that the viral load in the middle ear is lower than that present in the nasal cavity.

Predictors of academic career placement and scholarly impact in fellowship-trained rhinologists.

BACKGROUND: As rhinology fellowship positions outpace the availability of academic rhinology jobs, it is increasingly important to identify characteristics that are associated with academic placement after fellowship completion. In this study, we evaluated the association of academic characteristics during training with current job placement and posttraining scholarly impact. METHODS: Previous rhinology fellows were identified using publicly available data. Bibliometric indices, training institutions, graduate degrees, and job placement data were used in bivariate and multivariable regression analyses to assess for association with predictors and academic trajectory. RESULTS: Data from 265 rhinologists, all graduating between 1991 and 2020, were included. Most surgeons (n = 185, 70%) held an academic position and 80 (30%) surgeons worked in a nonacademic setting; 93.2% had a Doctor of Medicine (MD) degree and 80.3% were male. Multivariable logistic regression indicated that a designation of MD, compared with Doctor of Osteopathic Medicine (DO; odds ratio [OR], 5.93; 95% confidence interval [CI], 1.97-21.9), number of publications during fellowship (OR, 1.19; 95% CI, 1.02-1.41), and h-index during training (OR, 1.25; 95% CI, 1.07-1.49]) were independently predictive of academic job placement. Meanwhile, number of primary authorships during fellowship (ß = 1.47; 95% CI, 1.07-1.88]), h-index during training (ß = 0.48; 95% CI, 0.25-0.71), and PhD (ß = 4.16; 95% CI, 1.57-6.76) were associated with posttraining h-index. Medical school ranking; graduate degrees, including Master of Science (MS), Master of Business Administration (MBA), and Master of Public Health (MPH); and research metrics before residency were not associated with either academic placement or posttraining h-index. CONCLUSION: The predictors of academic job placement in rhinology are unclear, but h-index during training, and research productivity during fellowship may serve as indicators of an academic career.

Impact of Race, Ethnicity, and Socioeconomic Status on Nasopharyngeal Carcinoma Disease-Specific and Conditional Survival.

Introduction Race, ethnicity, and socioeconomic status (SES) are complex, interconnected social determinants of health outcomes. This study uses multivariable analysis on a combination of large national datasets to examine the effects of these factors on 5-year disease-specific survival (DSS) and conditional DSS (CDSS) for nasopharyngeal carcinoma (NPC). Methods A retrospective study of adults with NPC between 2000 and 2017 from the Surveillance, Epidemiology, End Results (SEER) registry was performed, using the National Cancer Institute Yost Index, a census tract-level composite score of SES to categorize patients. Kaplan-Meier analysis and Cox's regression for DSS and CDSS were stratified by SES. Logistic regression was conducted to identify risk factors for advanced cancer stage at time of diagnosis and receiving multimodal therapy. Results Our analysis included 5,632 patients. DSS was significantly associated with race and SES ( p < 0.01). Asian/Pacific Islander patients exhibited increased survival when controlling for other variables (hazard ratio [HR] = 0.73, p < 0.01). Although Black patients were more likely to be diagnosed with advanced disease (Black odds ratio [OR] = 1.47, p < 0.01), Black patients were also less likely to receive multimodal therapy; however, this relationship lost statistical significance once SES was incorporated into the multivariable analysis. DSS was decreased among the lowest (first) and middle (second) tertiles of SES (first HR = 1.34, p < 0.01; second HR = 1.20, p < 0.01) compared with the highest (third). Conclusion Our results indicate that race, ethnicity, and SES significantly affect survival, stage at diagnosis, and treatment of NPC. An interplay of tumor biology and inequalities in access to care likely drives these disparities.