Sinonasal Complications of Combined Transseptal-transnasal and Bilateral Transnasal Approaches for Endoscopic Endonasal Transsphenoidal Pituitary Surgery.

BACKGROUND: The endoscopic combined transseptal-transnasal technique for pituitary adenoma excision is notable for enhanced postoperative functional outcomes. Our study compared the incidence of anterior nasal septal perforation and the resulting sinonasal complications between this method and the bilateral transnasal approach. METHODS: Utilizing a retrospective cohort from a preeminent tertiary referral center, we analyzed 141 cases of endoscopic endonasal transsphenoidal surgery performed between March 2018 and May 2023. Outcomes for the transseptal-transnasal group (n = 71) and the conventional bilateral transnasal group (n = 70) were compared. Nasal endoscopy and computed tomography were used to assess anterior nasal septal perforation. Functional outcomes were assessed preoperatively and at 6 months postoperatively using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, Cross-Cultural Smell Identification Test (CCSIT), Sino-Nasal Outcome Test-22 (SNOT-22), and nasal obstruction symptom evaluation (NOSE) RESULTS: The transseptal-transnasal approach exhibited reduced rates of postoperative ear fullness (p < 0.001), along with fewer subjective complaints of smell/taste loss (p = 0.022) and thick nasal discharge (p = 0.008), compared to the conventional approach. However, objective smell test results were not significantly different between the two approaches (p = 0.243 and p = 0.454 for CCCRC and CCSIT, respectively). Additionally, although statistically insignificant, a higher incidence of anterior septal perforation was observed with the transseptal-transnasal approach (p = 0.067). CONCLUSION: For the surgical treatment of pituitary adenomas, the transseptal-transnasal approach offers several advantages over the bilateral transnasal method, particularly in reducing postoperative complications. However, this technique requires careful attention for preventing the occurrence of anterior septal perforation.

The lateral based nasopharyngeal flap: A novel vascularized flap for skull base reconstruction.

As the indications for endoscopic skull base approaches have increased, so has the need for more versatile vascularized flaps for skull base reconstruction. Here, we describe a novel lateral based nasopharyngeal flap (LNPF). Two cadaver heads were dissected to elucidate flap anatomy, dimensions, and technique. A retrospective review was performed on two cases where LNPF was used to repair CSF leaks in the nasopharyngeal area, and outcomes reported. The LNPF is an ascending pharyngeal artery myomucosal flap that includes the nasopharyngeal mucosa and the superior pharyngeal constrictor muscle. The flap was 1.2 × 2.2 cm in greatest dimensions. The LNPF was used for salvage CSF leak repair in two cases: one clival and one tubal. Both patients had resolution of leak at 7 months follow-up. The LNPF is a novel flap with reconstruction potential for the nasopharynx, including the lower clivus and the eustachian tube.

Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer.

The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1+ immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories. ASCL1 loss in RPM ONB leads to emergence of non-neuronal histopathologies, including a POU2F3+ microvillar-like state. Similar to small-cell lung cancer (SCLC), mouse and human ONBs exhibit mutually exclusive NEUROD1 and POU2F3-like states, an immune-cold tumor microenvironment, intratumoral cell fate heterogeneity comprising neuronal and non-neuronal lineages, and cell fate plasticity-evidenced by barcode-based lineage tracing and single-cell transcriptomics. Collectively, our findings highlight conserved similarities between ONB and neuroendocrine tumors with significant implications for ONB classification and treatment.

Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass.

OBJECTIVES: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. DESIGN: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. SETTING: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. PATIENTS: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index ( r = -0.225; ß = -0.037; p = 0.001 and proportion of perfused vessels: r = -0.17; ß = -0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O 2 /s/10 6 cells; p = 0.002). CONCLUSIONS: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.

Barosinusitis due to routine weather changes: A cross-sectional analysis of public websites.

Background: Sinusitis is a common diagnosis that can be erroneously associated with routine weather-related barometric pressure changes. In actuality, these pressure changes likely exacerbate migraine headaches, which can cause facial pain and pressure rather than true sinus inflammation. Objective: The present study sought to characterize the representation of both sinusitis and migraine in association with barometric pressure changes across websites on the Internet. Methods: An Internet search for relevant terms was conducted, and content of the resulting pages was assessed for associations between weather-related pressure changes and either sinusitis or migraine. Variations in reported results across different subtypes of Internet sources were analyzed. The primary outcomes measured were (1) whether a given media source associated barometric weather changes with sinusitis, (2) whether that source associated barometric weather changes with migraine, and (3) treatment options offered by that source. Results: Of the 116 included webpages, 36 (31.03%) associated sinusitis and routine barometric pressure changes. Of these, 10 (27.77%) were otolaryngology practice sites. Sixty-seven webpages (57.76%) associated migraine and routine barometric pressure changes. Of these, nonotolaryngology webpages were more likely to report this link. Conclusions: Otolaryngology practice sites were observed to be the most frequent professional medical resource reporting the unsubstantiated claim that routine barometric pressure changes are associated with sinusitis. Nonotolaryngology sources were more likely to link weather-related pressure changes to migraine. These results suggest that opportunities exist for otolaryngology practice sites to educate patients about nonrhinogenic headache etiologies.

Predictors of Non-Rhinogenic Facial Pain or Pressure in Otolaryngology Clinic.

OBJECTIVES: Identify demographic and clinical characteristics that may help differentiate non-rhinogenic facial pain or pressure (NRFP) from sinusitis. STUDY DESIGN: Retrospective single-institution study. SETTING: Tertiary Care Center Rhinology Clinic. METHODS: All patients presenting with a complaint of facial pain or pressure over a 3-year period were included. Patients were categorized into either NRFP or sinusitis groups based on computed tomography imaging and nasal endoscopy. Data pertaining to demographics, history, and SNOT-22 questionnaire domains were compared via univariate analysis as well as logistic regression with backwards variable selection. RESULTS: A total of 296 patients met inclusion criteria, of which 128 had NRFP and 168 had sinusitis. A significantly greater percentage of patients in the NRFP group were women of childbearing age (40.6% vs 28.0%, P = .02). Backwards variable selection resulted in a model with four variables predicting a diagnosis of NRFP-female sex (odds ratio [OR] = 2.998, P < .0001), no history of prior sinonasal surgery (OR = 0.340 for history vs no history, P < .01), low nasal domain score (OR = 0.551, P < .0001), and high ear/facial domain score (OR = 1.453, P < .01). CONCLUSION: Accurately identifying patients with NRFP at initial presentation based on history would help direct patients to the appropriate care pathway and prevent ineffective treatments such as antibiotics and sinus procedures. Our findings suggest that the suspicion for NRFP should be higher in women of child-bearing age as well as patients with greater ear/facial symptoms or lesser nasal symptoms.

Safety and Feasibility of Steroid-Eluting Stent as a Bolster in Endoscopic Anterior Skull Base Reconstruction.

BACKGROUND: With a rising incidence of cerebrospinal fluid (CSF) leaks, endoscopic endonasal CSF leak repair is increasingly performed. Current approaches utilize a variety of materials including free mucosal grafts and vascularized flaps, but post-op leaks continue to be reported. Steroid-eluting bioabsorbable stents (SES) are used during functional endoscopic sinus surgery for chronic rhinosinusitis to reduce inflammation and scarring while maintaining patency of sinus ostia. OBJECTIVE: The aim of this study is to assess the feasibility of SES as a graft/flap bolster for endoscopic endonasal CSF leak repair. METHODS: This is a retrospective review of patients undergoing endoscopic endonasal CSF leak repair with SES placed as part of the bolster technique at a tertiary care center between January 2019 and May 2022. Age, sex, BMI, comorbid idiopathic intracranial hypertension, pathology, location of CSF leak, intraoperative CSF leak flow, reconstruction type, and presence of post-op CSF leak were recorded. RESULTS: Twelve patients (mean age 52, median BMI 30.9, 58% female) had SES placement as part of the bolster technique. The most common pathology was meningoencephalocele (75%). Reconstruction was performed with either a free mucosal graft (6), or a flap (6). No post-op CSF leaks occurred at a reconstruction site with a stent, and no known complications were reported. All sinusotomies were patent at the last follow-up visit. CONCLUSIONS: SES placement as an adjunct to graft and/or flap bolster appears to be safe and feasible during anterior skull base reconstruction and CSF leak repair providing longer term structural support and preserving sinus drainage patency.

Nasopharyngeal Carcinoma: Case Presentation and Literature Review of Treatment Innovation with Immunotherapy.

Nasopharyngeal carcinoma (NPC), a rare head and neck malignancy, arises from the epithelial lining of nasopharyngeal mucosa. The confluence of various risk factors, such as latent Epstein-Barr virus infection, genetic susceptibility, smoking, alcohol consumption, and high nitrosamine diet, is thought to contribute to NPC pathogenesis. Radiation therapy serves as the mainstay of treatment for early stage while concurrent chemotherapy and radiation are the basis of treatment for locoregional advanced disease with overall 80% five-year survival rate. Recurrent or metastatic disease pose treatment challenges as reirradiation, repeat cycles of chemotherapy, and surgery follow with high likelihood of treatment toxicity or postoperative morbidities. Typically reserved for nonresectable recurrent or metastatic disease, immunotherapy serves as novel treatment for NPC. NPC tumor microenvironment predominated by a dense infiltrate of immune cells hosts an ideal target for immunotherapy. Several clinical trials have investigated the efficacy of anti-programmed cell death protein 1 antibodies such as pembrolizumab, nivolumab, and camrelizumab with promising results. Treatment of recurrent and metastatic NPC remains a challenge; however, the advent of immunotherapy has provided additional options and potential for preventative and therapeutic measures.

Preparation of Human Olfactory Epithelial Biopsies for Downstream Analysis.

The olfactory mucosa, lining a portion of the nasal cavity, houses the primary olfactory sensory neurons responsible for odor transduction, along with supporting cell populations. Tremendous advances have come from studying the peripheral olfactory system in animal models, especially the mouse. However, acquired human olfactory disorders lack effective therapies, and many of these conditions involve pathology in the olfactory mucosa. Thus, the ability to obtain human olfactory biopsy samples from subjects with olfactory dysfunction, or controls, may be of value. Here, we describe established techniques for collecting olfactory tissue from human subjects and preparing samples for downstream assays such as immunohistochemistry, flow cytometry, single-cell RNA-sequencing, or chromatin studies.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

INTRODUCTION: Microcirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. METHODS: Adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. RESULTS: Of 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). CONCLUSIONS: Poor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Use of Tympanostomy T-Tube for Endoscopic Endonasal Marsupialization of Small Rathke's Cleft Cysts: A Case Series.

Objectives This article describes a novel technique implementing the use of a tympanostomy t-tube to provide long-term marsupialization of small Rathke's cleft cysts (RCCs). Design A retrospective review of electronic medical records was performed to collect demographic and clinical data on a series of four patients. Setting Academic medical center. Participants Four female patients (mean age of 34 years) underwent transsphenoidal endoscopic endonasal surgery for RCC. All four patients presented with headaches. Mean cyst size was 7 mm. Two of the four surgeries were revisions for RCC recurrence. Main Outcome Measures Symptom resolution after surgery, duration of follow-up, and feasibility of the proposed technique. Results Tympanostomy t-tube was used to marsupialize small RCCs (< 10 mm) for four patients. Three patients remained symptom-free with endoscopy and imaging showing patent t-tubes at 21 months' (range 20-24 months) follow-up. One patient experienced severe migraines immediately after surgery. Migraines were relieved after t-tube was removed 6 weeks after surgery. Conclusion Tympanostomy t-tubes placed via an endoscopic endonasal approach can provide long-term marsupialization for small RCCs.

Deconstructing Olfactory Epithelium Developmental Pathways in Olfactory Neuroblastoma.

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T-cell identities in high-grade tumors (GBC from ∼0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman's gland, and olfactory ensheathing programs, in high-grade tumors (mature neuronal from 3.7% to ∼0%, Bowman's gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression. Significance: Our analyses provide a basis for additional research on olfactory neuroblastoma management, as well as identification of potential new prognostic markers.

Characterizing Olfactory Dysfunction in Patients with Unilateral Cleft Lip Nasal Deformities.

Background: Unilateral cleft lip nasal deformity (uCLND) is associated with olfactory dysfunction, but the underlying etiology remains poorly understood. Objective: To investigate the etiology of uCLND-associated olfactory dysfunction using clinical, computational, and histologic assessments. Methods: Inclusion criteria: uCLND patients >16 years undergoing septorhinoplasty. Exclusion criteria: prior septoplasty or rhinoplasty, pregnancy, sinusitis. Measured outcomes: patient-reported scores, rhinomanometry, smell identification and threshold tests, computational fluid dynamics (CFD) airflow simulations, and histologic analysis of olfactory epithelium. Results: Five uCLND subjects were included: 18-23 years, three male and two female, four left-sided cleft and one right-sided cleft. All subjects reported moderate to severe nasal obstruction. Smell identification and threshold tests showed varying degrees of hyposmia. Nasal resistance was higher on the cleft side versus noncleft side measured by rhinomanometry (median 3.85 Pa-s/mL, interquartile range [IQR] = 21.96, versus 0.90 Pa-s/mL, IQR = 5.17) and CFD (median 1.04 Pa-s/mL, IQR = 0.94 vs. 0.11 Pa-s/mL, IQR = 0.12). Unilateral olfaction varied widely and was dependent on unilateral percentage olfactory airflow. Biopsies revealed intact olfactory neuroepithelium. Conclusions: uCLND-associated olfactory dysfunction appears to be primarily conductive in etiology and highly susceptible to variations in nasal anatomy. Clinical Trial Registration number: NCT04150783.

Alteration in Cerebral Metabolism in a Rodent Model of Acute Sub-lethal Cyanide Poisoning.

INTRODUCTION: Cyanide exposure can occur in various settings such as industry and metallurgy. The primary mechanism of injury is cellular hypoxia from Complex IV (CIV) inhibition. This leads to decreased ATP production and increased reactive oxygen species production. The brain and the heart are the organs most affected due to their high metabolic demand. While the cardiac effects of cyanide are well known, the cerebral effects on cellular function are less well described. We investigated cerebral metabolism with a combination of brain respirometry, microdialysis, and western blotting using a rodent model of sub-lethal cyanide poisoning. METHODS: Twenty rodents were divided into two groups: control (n = 10) and sub-lethal cyanide (n = 10). Cerebral microdialysis was performed during a 2 mg/kg/h cyanide exposure to obtain real-time measurements of cerebral metabolic status. At the end of the exposure (90 min), brain-isolated mitochondria were measured for mitochondrial respiration. Brain tissue ATP concentrations, acyl-Coenzyme A thioesters, and mitochondrial content were also measured. RESULTS: The cyanide group showed significantly increased lactate and decreased hypotension with decreased cerebral CIV-linked mitochondrial respiration. There was also a significant decrease in cerebral ATP concentration in the cyanide group and a significantly higher cerebral lactate-to-pyruvate ratio (LPR). In addition, we also found decreased expression of Complex III and IV protein expression in brain tissue from the cyanide group. Finally, there was no change in acyl-coenzyme A thioesters between the two groups. CONCLUSIONS: The key finding demonstrates mitochondrial dysfunction in brain tissue that corresponds with a decrease in mitochondrial function, ATP concentrations, and an elevated LPR indicating brain dysfunction at a sub-lethal dose of cyanide.

SNOT-22 Quality of Life Scores Improve After Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Rhinorrhea.

OBJECTIVES: Patients with spontaneous cerebrospinal fluid (CSF) rhinorrhea can experience significant sinonasal symptom burden, leading to poor quality of life (QOL). The objective of this study was to investigate sinonasal outcome test-22 (SNOT-22) scores in patients undergoing endoscopic endonasal surgery for spontaneous CSF rhinorrhea and compare them to patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis without nasal polyps (CRSsNP). METHODS: A multi-institutional retrospective review of patients with spontaneous CSF rhinorrhea and CRSsNP was performed. Pre-surgery and post-surgery SNOT-22 scores and domains were compared within each group. Improvements in SNOT-22 scores after surgery were compared between the groups. RESULTS: Ninety-one patients were in the CSF rhinorrhea group and 105 patients were in the CRSsNP group. Within each group, surgery significantly improved total SNOT-22 scores, domain scores, and most of the individual symptoms. Comparing the 2 groups revealed similar improvements in total SNOT-22 scores (P = .244). The CSF rhinorrhea group improved more in runny nose (P < .001), postnasal discharge (P < .001), wake up at night (P = .024), and embarrassed (P = .002). The CRSsNP group improved more in sneezing (P = .027), nasal blockage (P < .001), decreased sense of smell/taste (P = .011), thick nasal discharge (P < .001), facial pain/pressure (P = .008), and the ear/facial domain (P = .010). CONCLUSIONS: Patients with spontaneous CSF rhinorrhea experience significant symptom burden. Those who undergo CSF leak repair should experience significant improvement in QOL similar to patients who undergo ESS for CRSsNP as measured by SNOT-22.

Individual SNOT-22 Items Aid in Differentiating Between Spontaneous Cerebrospinal Fluid Rhinorrhea and Chronic Rhinosinusitis Without Nasal Polyps.

OBJECTIVES: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)-22 could suggest a diagnosis of spontaneous CSF rhinorrhea versus chronic rhinosinusitis without nasal polyps (CRSsNP). METHODS: A multi-institutional retrospective chart review of patients with spontaneous CSF rhinorrhea and a control group of CRSsNP patients was performed. Individual SNOT-22 scores and domain scores were compared. RESULTS: One hundred fifteen patients were included in both cohorts. Of the patients in the CSF rhinorrhea group, 48% were misdiagnosed as chronic rhinosinusitis (CRS) prior to the correct identification of a CSF leak. On bivariate analysis, the CSF rhinorrhea group scored significantly higher on the SNOT-22 for runny nose (P < .001) and was more likely to designate this symptom as most important (P < .001). The CRSsNP group scored significantly higher in nasal blockage (P < .001), thick nasal discharge (P < .001), facial pain/pressure (P < .001), and in the ear/facial (P < .001) and rhinologic (P = .003) domains. Multivariable logistic regression revealed that runny nose (P < .001) was most predictive of spontaneous CSF rhinorrhea while nasal blockage (P < .001), thick nasal discharge (P < .001), and facial pain/pressure (P = .001) were predictive of CRSsNP after adjusting for relevant confounders. No significant difference was observed in total SNOT-22 scores between groups (P = .676). CONCLUSIONS: Spontaneous CSF rhinorrhea is commonly misdiagnosed as other sinonasal pathologies. However, individual SNOT-22 items can help aid in suggesting a CSF leak. Spontaneous CSF rhinorrhea should be suspected in patients who have high SNOT-22 scores for runny nose and report this symptom as most important, but have lower scores related to the other cardinal symptoms of CRS.

Nasal Cavity Squamous Cell Carcinoma: Factors Associated With Treatment Outcomes and Potential Organ Preservation.

BACKGROUND: Squamous cell carcinoma of the nasal cavity (NCSCC) is a rare, challenging malignancy. Surgical resection of this tumor can cause significant facial deformity, and indications for adjuvant or organ preservation therapies are not well-described. OBJECTIVE: To examine the impact of treatment regimen on survival outcomes in NCSCC and to compare surgical to non-surgical based therapies. METHODS: The National Cancer Database was queried for NCSCC from 2004 to 2014. Patient demographics, tumor characteristics, and treatment regimen were compared for the entire cohort. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen and surgical margins on overall survival (OS) for early and late-stage disease. RESULTS: A total of 1883 NCSCC patients were identified. The OS for the cohort was 83 months, and median age at diagnosis was 65 years. NCSCC patients who underwent surgery followed by adjuvant radiation therapy (RT) had a better OS compared to definitive RT (HR: 0.58, P < .001). In early stage NCSCC (T1/T2, N0), there was no significant difference in OS between patients treated with surgery only or surgery with adjuvant RT compared to definitive RT. In advanced stage NCSCC, surgery with adjuvant RT had a better OS compared to definitive chemoradiation. Having positive margins was shown to predict a worse OS when compared to negative margins in surgical patients despite adjuvant RT or chemoradiation. CONCLUSIONS: NCSCC appears to be best treated with surgery followed by adjuvant RT in advanced-stage disease whereas in early-stage disease, surgery does not improve OS compared to definitive RT.

Persistent post-COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium.

SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how SARS-CoV-2 causes persistent smell loss in a subset of patients. To address this question, we analyzed olfactory epithelial samples collected from 24 biopsies, including from nine patients with objectively quantified long-term smell loss after COVID-19. This biopsy-based approach revealed a diffuse infiltrate of T cells expressing interferon-γ and a shift in myeloid cell population composition, including enrichment of CD207+ dendritic cells and depletion of anti-inflammatory M2 macrophages. Despite the absence of detectable SARS-CoV-2 RNA or protein, gene expression in the barrier supporting cells of the olfactory epithelium, termed sustentacular cells, appeared to reflect a response to ongoing inflammatory signaling, which was accompanied by a reduction in the number of olfactory sensory neurons relative to olfactory epithelial sustentacular cells. These findings indicate that T cell-mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post-COVID-19 smell loss.

Retrospective Review of Surgical Site Infections after Endoscopic Endonasal Sellar and Parasellar Surgery: Multicenter Quality Data from the North American Skull Base Society.

Introduction Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes. Methods We conducted a multicenter retrospective analysis of shared quality data points for the endoscopic endonasal approach (EEA) for pituitary adenomas, along with other sellar and parasellar region masses that were included by participating institutions. Patient and operative characteristics, perioperative and postoperative antibiotic regimens and their durations, intraoperative and postoperative cerebrospinal fluid leak, and onset of postoperative meningitis and sinusitis were compared. Results Fifteen institutions participated and provided 6 consecutive months' worth of case data. Five hundred ninety-three cases were included in the study, of which 564 were pituitary adenomectomies. The incidences of postoperative meningitis and sinusitis were low (0.67 and 2.87% for all pathologies, respectively; 0.35% meningitis for pituitary adenomas) and did not correlate with any specific antibiotic regimen. Immunocompromised status posed an increased odds of meningitis in pituitary adenomectomies (28.6, 95% confidence interval [1.72-474.4]). Conclusions The results show no clear benefit to postoperative antimicrobial use in EEA, with further larger studies needed.

Zinc's Association with the CmPn/CmP Signaling Network in Breast Cancer Tumorigenesis.

It is well-known that serum and cellular concentrations of zinc are altered in breast cancer patients. Specifically, there are notable zinc hyper-aggregates in breast tumor cells when compared to normal mammary epithelial cells. However, the mechanisms responsible for zinc accumulation and the consequences of zinc dysregulation are poorly understood. In this review, we detailed cellular zinc regulation/dysregulation under the influence of varying levels of sex steroids and breast cancer tumorigenesis to try to better understand the intricate relationship between these factors based on our current understanding of the CmPn/CmP signaling network. We also made some efforts to propose a relationship between zinc signaling and the CmPn/CmP signaling network.