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OBJECTIVES: There is growing interest in assessing patient quality of life (QOL) following treatment of sinonasal tumors, including inverted papilloma (IP). We aimed to elucidate the natural history of postoperative QOL outcomes in IP patients treated with surgery. METHODS: Cases of sinonasal IP treated surgically at 4 tertiary academic rhinology centers were retrospectively reviewed. SNOT-22 scores were used to evaluate QOL preoperatively and postoperatively (1, 3, 6, 12 months). Repeated-measures ANOVA assessed for differences in mean scores over time. Linear regression identified factors associated with QOL longitudinally. RESULTS: 373 patients were analyzed. Mean preoperative SNOT-22 score was 20.6 ± 20.4, which decreased to 16.3 ± 18.8 (p = 0.041) and 11.8 ± 15.0 (p < 0.001) at 1 and 3 months postoperatively, respectively. No further changes in SNOT-22 scores occurred beyond 3 months postoperatively (p > 0.05). When analyzed by SNOT-22 subdomains, nasal, sleep, and otologic/facial subdomain scores (all p < 0.05) demonstrated improvement at 12-month follow-up compared with preoperative scores; this was not observed for the emotional subdomain score (p = 0.800). Recurrent cases were associated with higher long-term SNOT-22 scores (ß = 7.08; p = 0.017). Age, sex, degree of dysplasia, prior surgery, primary site, and smoking history did not correlate with symptoms (all p > 0.05). CONCLUSIONS: QOL outcomes related to IP resection are largely driven by nasal, sleep, and otologic/facial subdomains, though patients appear to experience enduring improvement as early as 3 months postoperatively. Recurrent disease is a major driver of negative QOL. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.
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OBJECTIVES: Endoscopic sinus surgery (ESS) is often necessary when managing odontogenic sinusitis (ODS), but ESS extent for ODS with extramaxillary sinus involvement has been incompletely studied. This study compared outcomes after wide maxillary antrostomy (MA) alone versus complete ESS for ODS with frontal sinus involvement. METHODS: A multicenter prospective cohort study was conducted on patients with uncomplicated ODS (no extrasinus spread) who underwent ESS when computed tomography demonstrated maxillary, anterior ethmoid (AE), and frontal sinus opacification. Multiple preoperative and postoperative variables were recorded, including 22-item sinonasal outcome tests (SNOT-22) and endoscopic findings. Ultimate SNOT-22 and endoscopic resolution, and time to SNOT-22 and endoscopic resolution were compared between patients who underwent MA alone versus "complete" ESS (maxillary, ethmoid, frontal; not sphenoid). RESULTS: Of 70 patients, mean age was 59.2 years, and 55.7% were male. Thirty-five underwent MA alone, and 35 had complete ESS. At first postoperative visits (mean 9.3 days), AE sinus purulence was more likely resolved after complete ESS compared with MA (97.1% vs. 71.4%, p = 0.006). However, time to resolution of AE purulence was comparable by 6 weeks postoperatively (p = 0.158). There were no significant differences in times to foul smell resolution and achieving ≥9 point SNOT-22 reduction (p > 0.05). CONCLUSIONS: For ODS with frontal sinus involvement, MA alone and complete ESS both resulted in rapid and long-term symptomatic resolution. While ultimate resolution of sinus purulence was equivalent between surgery groups, complete ESS did lead to faster resolution of frontoethmoidal purulence in a significant number of cases. LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.
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BACKGROUND: The inability of topical medications to reach sinus cavities is a potential reason for lack of efficacy in chronic rhinosinusitis (CRS). One purpose of endoscopic sinus surgery (ESS) is to enable delivery of medications into the sinus cavities. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE) creates unique biomechanics that enable deposition of intranasal corticosteroid into sinuses and sinus drainage pathways but may have differing efficacy in operated versus unoperated sinuses. Two 24-week randomized trials (ReOpen1/2) evaluated EDS-FLU versus EDS-placebo in patients with CRS, stratified by surgical status. METHODS: Surgery-naive (n = 332) and prior-surgery (n = 215) patient groups were analyzed as pooled data from ReOpen1/2. Outcome measures (least-squares mean change from baseline) included combined symptom score (CSS) and congestion score at weeks 4, 8, and 12 and average of percentages of opacified volume (APOV) of ethmoid/maxillary sinuses on CT and Sinonasal Outcome Test 22 (SNOT-22) total score at week 24. RESULTS: Baseline scores suggested moderate-severe disease: mean CSS = 5.8; APOV = 67.2%. EDS-FLU produced significant improvement versus placebo (p < 0.05): CSS (surgery-naive, -0.68 vs. -1.42; prior ESS, -0.70 vs. -1.87); congestion (surgery-naive, -0.24 vs. -0.59; prior ESS, -0.24 vs. -0.69); and SNOT-22 (surgery-naive, -7.56 vs. -18.30; prior ESS, -10.72 vs. -18.74). Similar results were observed for APOV (p < 0.05). No statistically significant difference was observed between surgery subgroups with either EDS-FLU dose. CONCLUSION: EDS-FLU improved symptoms, sinus opacification, and quality of life in patients with CRS with or without prior ESS, suggesting a role for EDS-FLU in both populations.
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KEY POINTS: Inverted papilloma conversion to squamous cell carcinoma is not always easy to predict. AutoML requires much less technical knowledge and skill to use than traditional ML. AutoML surpassed the traditional ML algorithm in differentiating IP from IP-SCC.
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BACKGROUND: Empty nose syndrome (ENS) is a poorly understood, debilitating condition affecting a minority of patients who underwent nasal airway surgery, most commonly following inferior turbinate surgery. Few publications have demonstrated middle turbinate resection (MTR) causing ENS, but MTR is still considered a potential cause of ENS. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) is validated for ENS diagnosis, with ENS6Q ≥ 11 considered highly suggestive of ENS. The purpose of this multicenter study was to determine the incidence of patients with ENS6Q ≥ 11 following subtotal MTR during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing preoperative and postoperative ENS6Q scores. METHODS: A multi-institutional prospective cohort study (8 US institutions) was conducted on patients who underwent bilateral subtotal MTR during ESS for CRSwNP. Preoperative and postoperative ENS6Q scores were compared after at least 12 months of postoperative follow-up. RESULTS: Of 110 patients, mean age was 51.6 years and 59.1% were male. Mean follow-up was 14.5 ± 2.5 months (range 12.1-22.3 months). Mean preoperative and postoperative ENS6Q were 7.7 and 2.2, respectively, demonstrating a mean 5.5 point decrease postoperatively (p < 0.0001). At final follow-up, no patient had an ENS6Q ≥ 11. Of note, 20% of patients had preoperative ENS6Q scores ≥11, but all decreased to <11 postoperatively. CONCLUSIONS: Based on prospective multicenter data over 1-2 years postoperatively, subtotal MTR for CRSwNP never led to ENS6Q scores ≥11, and patients experienced significant decreases in ENS6Q postoperatively. Subtotal MTR during ESS for CRSwNP was, therefore, unlikely to cause ENS even with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.
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BACKGROUND: Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase-11 (MMP-11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP-11 in IP epithelial migration and invasion. METHODS: Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP-derived epithelial cultures and normal mucosa-derived epithelial cultures were grown in airâliquid interface, followed by immunostaining to assess MMP-11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti-MMP-11 antibody on IP and control epithelial cultures. RESULTS: IP-derived cultures demonstrated strong MMP-11 expression compared to controls. Treatment with anti-MMP-11 blocking antibody significantly reduced epithelial migration only in IP-derived cells compared to non-treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP-11 reduced IP epithelia's ability to invade through collagen-coated transwells, suggesting that MMP-11 plays a role in invasion. CONCLUSION: We established an in vitro model to study IP-derived epithelial cells. MMP-11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP-11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP-11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP-11 has a role in malignant transformation of IP.
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BACKGROUND: Sinonasal malignancy surveillance paradigms are often based on Head and Neck National Comprehensive Cancer Network guidelines, which do not recommend standard surveillance imaging beyond 6 months without concerning symptomatology or physical examination findings. METHODS: This was a retrospective analysis of all patients who underwent resection of sinonasal malignancy at a tertiary care center over a 20-year period from 2000 to 2020, with an ensuing surveillance period demonstrating recurrence. RESULTS: Fifty-two patients with sinonasal malignancy recurrence were included, with an average time to recurrence of 30.9 months and a follow-up period of over 60 months. Recurrence was diagnosed by routine imaging or endoscopy in asymptomatic patients in a majority (60%) of cases, while the remaining minority of diagnoses followed new symptomatology. Asymptomatic recurrence was associated with perineural spread of tumor at initial resection (p = 0.025), but not with age (p = 0.85) or stage at diagnosis (p = 0.68). Expectedly, positron emission tomography/computed tomography (CT) more often detected regional or distant recurrence, while structural imaging (CT/magnetic resonance imaging) demonstrated more frequent detection of recurrence in those with perineural spread of tumor (p = 0.01). CONCLUSIONS: Our findings support high rates of asymptomatic recurrence in sinonasal malignancy, with the majority of recurrences diagnosed by routine endoscopy or imaging. Tailored and extended surveillance guidelines are necessary relative to those utilized for other head and neck mucosal cancers, and are especially appropriate when features such as perineural spread are present.
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INTRODUCTION: Chronic rhinosinusitis (CRS) can be associated with tumors involving the maxillary sinus, but outcomes after undergoing maxillectomy with free flap reconstruction remain unclear. METHODS: A retrospective analysis of medical records was performed to evaluate evidence of CRS in patients who underwent maxillectomy with free flap reconstruction at a single tertiary care academic institution from 2013 through 2020. RESULTS: Eighty-four patients were assessed. Nineteen (22.6%) patients were diagnosed with CRS after surgery, 23 (27.4%) patients were treated for sinus symptoms, and 49 (58.3%) had radiographic evidence of sinus inflammation for more than 6 months. Risk factors for requiring sinus treatment included adjuvant or neoadjuvant chemotherapy (p = 0.002) and pre-operative use of sinus medication (p < 0.001). Radiographic evidence of sinusitis 6 months after surgery is also closely associated with sinusitis treatment (p = 0.051). CONCLUSIONS: CRS may be underdiagnosed in patients undergoing maxillectomy with microvascular reconstruction. Further evaluation into patient sinus disease and symptoms following neoplastic surgery may lead to a higher quality of life in some long-term survivors.
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PURPOSE: Sinonasal malignancies (SNMs) adversely impact patients' quality of life (QOL) and are frequently identified at an advanced stage. Because these tumors are rare, there are few studies that examine the specific QOL areas that are impacted. This knowledge would help improve the care of these patients. METHODS: In this prospective, multi-institutional study, 273 patients with SNMs who underwent definitive treatment with curative intent were evaluated. We used the University of Washington Quality of Life (UWQOL) instrument over 5 years from diagnosis to identify demographic, treatment, and disease-related factors that influence each of the 12 UWQOL subdomains from baseline to 5 -years post-treatment. RESULTS: Multivariate models found endoscopic resection predicted improved pain (vs. nonsurgical treatment CI 2.4, 19.4, p = 0.01) and appearance versus open (CI 27.0, 35.0, p < 0.001) or combined (CI 10.4, 17.1, p < 0.001). Pterygopalatine fossa involvement predicted worse swallow (CI -10.8, -2.4, p = 0.01) and pain (CI -17.0, -4.0, p < 0.001). Neck dissection predicted worse swallow (CI -14.8, -2.8, p < 0.001), taste (CI -31.7, -1.5, p = 0.02), and salivary symptoms (CI -28.4, -8.6, p < 0.001). Maxillary involvement predicted worse chewing (CI 9.8, 33.2; p < 0.001) and speech (CI -21.8, -5.4, p < 0.001) relative to other sites. Advanced T stage predicted worse anxiety (CI -13.0, -2.0, p = 0.03). CONCLUSIONS: Surgical approach, management of cervical disease, tumor extent, and site of involvement impacted variable UWQOL symptom areas. Endoscopic resection predicted better pain, appearance, and chewing compared with open. These results may aid in counseling patients regarding potential QOL expectations in their SNM treatment and recovery course.
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Akt is an important kinase in metabolism. Akt also phosphorylates and activates endothelial and neuronal nitric oxide (NO) synthases (eNOS and nNOS, respectively) expressed in M0 (unpolarized) macrophages. We showed that e/nNOS NO production downstream of bitter taste receptors enhances macrophage phagocytosis. In airway epithelial cells, we also showed that the activation of Akt by a small molecule (SC79) enhances NO production and increases levels of nuclear Nrf2, which reduces IL-8 transcription during concomitant stimulation with Toll-like receptor (TLR) 5 agonist flagellin. We hypothesized that SC79's production of NO in macrophages might likewise enhance phagocytosis and reduce the transcription of some pro-inflammatory cytokines. Using live cell imaging of fluorescent biosensors and indicator dyes, we found that SC79 induces Akt activation, NO production, and downstream cGMP production in primary human M0 macrophages. This was accompanied by a reduction in IL-6, IL-8, and IL-12 production during concomitant stimulation with bacterial lipopolysaccharide, an agonist of pattern recognition receptors including TLR4. Pharmacological inhibitors suggested that this effect was dependent on Akt and Nrf2. Together, these data suggest that several macrophage immune pathways are regulated by SC79 via Akt. A small-molecule Akt activator may be useful in some infection settings, warranting future in vivo studies.
Subject(s)
Cytokines , Macrophages , Nitric Oxide , Phagocytosis , Proto-Oncogene Proteins c-akt , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phagocytosis/drug effects , Macrophages/metabolism , Macrophages/drug effects , Cytokines/metabolism , Nitric Oxide/metabolism , NF-E2-Related Factor 2/metabolism , Cyclic GMP/metabolism , Lipopolysaccharides/pharmacologyABSTRACT
Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine malignancy arising from the olfactory neuroepithelium. ONB frequently presents with nonspecific sinonasal complaints, including nasal obstruction and epistaxis, and diagnosis can be obtained through a combination of physical examination, nasal endoscopy, and computed tomography and magnetic resonance imaging. Endoscopic resection with negative margins, with or without craniotomy, as necessary, is the standard of care for definitive treatment of ONB. Regional metastasis to the neck is often detected at presentation or may occur in a delayed fashion and should be addressed through elective neck dissection or radiation. Adjuvant radiotherapy should be considered, particularly in the case of high grade or tumor stage, as well as positive surgical margins. Systemic therapy is an area of active investigation in both the neoadjuvant and adjuvant setting, with many advocating in favor of induction chemotherapy for significant orbital or intracranial involvement prior to surgical resection. Various targeted immunotherapies are currently being studied for the treatment of recurrent or metastatic ONB. Prolonged locoregional and distant surveillance are indicated following definitive treatment, given the tendency for delayed recurrence and metastasis.
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Odontogenic cysts impact the adjacent dentition and maxillary sinus. A combined transnasal, transoral approach for removal offers reduced recurrence rates and favorable sinonasal outcomes compared with historic transoral-only approaches.
Subject(s)
Odontogenic Cysts , Humans , Male , Female , Odontogenic Cysts/surgery , Adult , Middle Aged , Treatment Outcome , Recurrence , Retrospective Studies , Natural Orifice Endoscopic Surgery/methods , Mouth/surgery , Aged , Adolescent , Young AdultABSTRACT
OBJECTIVE: Surgical frailty estimates a patient's ability to withstand the physiologic stress of an intervention. There is limited data regarding the impact of frailty on endoscopic cerebrospinal fluid (CSF) leak repair. METHODS: Patients undergoing CSF leak repair at two tertiary academic skull base programs were retrospectively reviewed. Demographic, treatment, and postoperative outcomes data were recorded. Frailty was calculated using validated indices, including the American Society of Anesthesiologists (ASA) classification, Charlson Comorbidity Index (CCI), and the Modified 5-Item Frailty Index (mFI-5). Outcomes included 30-day medical and surgical complications and readmission. RESULTS: A total of 185 patients were included with 128 (69.2%) female patients and average age of 54 ± 14 years. The average body mass index was 34.6 ± 8.5. The most common identified etiology was idiopathic intracranial hypertension (IIH) in 64 patients (34.6%). A total of 125 patients (68%) underwent perioperative lumbar drain placement (primarily to measure intracranial pressures and diagnose IIH). Most patients were ASA class 3 (48.6%) with mean CCI 2.14 ± 2.23 and mFI-5 0.97 ± 0.90. Three patients had postoperative CSF leaks, with an overall repair success rate of 98.4%. There was no association between increased frailty and 30-day medical outcomes, surgical outcomes, or readmission (all p > 0.05). CONCLUSIONS: Endoscopic CSF leak repair in a frail population, including lumbar drain placement and bed rest, was not associated with an increased rate of complications. Previous data suggests increased complications in open craniotomy procedures in patients with significant comorbidities. This study suggests that the endoscopic approach to CSF leak repair is well tolerated in the frail population. LEVEL OF EVIDENCE: IV Laryngoscope, 134:2713-2717, 2024.
Subject(s)
Cerebrospinal Fluid Leak , Endoscopy , Frailty , Skull Base , Humans , Female , Male , Middle Aged , Retrospective Studies , Cerebrospinal Fluid Leak/surgery , Cerebrospinal Fluid Leak/etiology , Skull Base/surgery , Frailty/complications , Endoscopy/methods , Treatment Outcome , Postoperative Complications/etiology , Postoperative Complications/surgery , Aged , AdultABSTRACT
BACKGROUND: Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22-item Sinonasal Outcomes Test (SNOT-22) has been shown to improve with treatment. This study aims to characterize SNOT-22 subdomain outcomes in SNM. METHODS: Patients diagnosed with SNM were prospectively enrolled in a multi-center patient registry. SNOT-22 scores were collected at the time of diagnosis and through the post-treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT-22 subdomains. RESULTS: Note that 234 patients were reviewed, with a mean follow-up of 22 months (3 months-64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow-up at all timepoints showed statistically significant improvement in rhinologic, extra-nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69-8.66])), extra-nasal (2.21 [0.22-4.17]) and ear/facial (5.53 [2.10-8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54-5.93]) and ear/facial (2.97 [0.32-5.65]) subdomains. Positive margins (5.74 [2.17-9.29]) and surgical approach-combined versus endoscopic (3.41 [0.78-6.05])-were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18-4.40]) was associated with worse sleep outcomes. CONCLUSIONS: Sinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra-nasal, psychological, and sleep subdomains.
Subject(s)
Paranasal Sinus Neoplasms , Quality of Life , Humans , Male , Female , Middle Aged , Prospective Studies , Aged , Paranasal Sinus Neoplasms/surgery , Paranasal Sinus Neoplasms/therapy , Sino-Nasal Outcome Test , Treatment Outcome , AdultABSTRACT
There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy.
Subject(s)
Eosinophilia , Nasal Polyps , Rhinitis , Sinusitis , Humans , Sinusitis/surgery , Rhinitis/surgery , Macrolides/therapeutic use , Chronic Disease , Eosinophilia/complications , Anti-Bacterial Agents/therapeutic use , Nasal Polyps/complicationsABSTRACT
BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays. OBJECTIVE: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps). METHODS: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24. RESULTS: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids. CONCLUSIONS: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status.
Subject(s)
Nasal Polyps , Rhinitis , Rhinosinusitis , Sinusitis , Adult , Humans , Chronic Disease , Fluticasone/therapeutic use , Nasal Polyps/drug therapy , Nasal Polyps/chemically induced , Randomized Controlled Trials as Topic , Rhinitis/drug therapy , Rhinitis/chemically induced , Sinusitis/drug therapy , Sinusitis/chemically induced , Steroids/therapeutic useABSTRACT
BACKGROUND: The role of Akt in nasal immunity is unstudied. Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) expressed in epithelial ciliated cells. Nitric oxide (NO) production by ciliated cells can have antibacterial and antiviral effects. Increasing nasal NO may be a useful antipathogen strategy in chronic rhinosinusitis (CRS). We previously showed that small-molecule Akt activator SC79 induces nasal cell NO production and suppresses IL-8 via the transcription factor Nrf-2. We hypothesized that SC79 NO production may additionally have antibacterial effects. METHODS: NO production was measured using fluorescent dye DAF-FM. We tested effects of SC79 during co-culture of Pseudomonas aeruginosa with primary nasal epithelial cells, using CFU counting and live-dead staining to quantify bacterial killing. Pharmacology determined the mechanism of SC79-induced NO production and tested dependence on Akt. RESULTS: SC79 induced dose-dependent, Akt-dependent NO production in nasal epithelial cells. The NO production required eNOS and Akt. The NO released into the airway surface liquid killed P. aeruginosa. No toxicity (LDH release) or inflammatory effects (IL8 transcription) were observed over 24 h. CONCLUSIONS: Together, these data suggest multiple immune pathways are stimulated by SC79, with antipathogen effects. This in vitro pilot study suggests that a small-molecule Akt activator may have clinical utility in CRS or respiratory other infection settings, warranting future in vivo studies.
Subject(s)
Epithelial Cells , Nasal Mucosa , Nitric Oxide , Proto-Oncogene Proteins c-akt , Pseudomonas aeruginosa , Humans , Nitric Oxide/metabolism , Nasal Mucosa/immunology , Nasal Mucosa/metabolism , Nasal Mucosa/cytology , Proto-Oncogene Proteins c-akt/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/immunology , Cells, Cultured , Nitric Oxide Synthase Type III/metabolism , Anti-Bacterial Agents/pharmacology , Rhinitis/immunology , Rhinitis/microbiology , Rhinitis/drug therapyABSTRACT
OBJECTIVE: Frailty metrics estimate a patient's ability to tolerate physiologic stress and there are limited frailty data in patients undergoing expanded endonasal approaches (EEA) for suprasellar pathologies. Elevated frailty metrics have been associated with increased perioperative complications in patients undergoing craniotomies. We sought to examine this potential relationship in EEA. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary academic skull base centers. METHODS: Cases of patients undergoing EEA for suprasellar pathologies were reviewed. Demographic, treatment, survival, and postoperative outcomes data were recorded. Frailty was calculated using validated indexes, including the American Society of Anesthesiologists (ASA) classification, the modified 5-item frailty index (mFI-5), and the Charlson comorbidity index (CCI). Primary outcomes included 30-day medical and surgical complications. RESULTS: A total of 88 patients were included, with 59 (67%) female patients and a mean age of 54 ± 15 years. The most common pathologies included 53 meningiomas (60.2%) and 21 craniopharyngiomas (23.9%). Most patients were ASA class 3 (54.5%) with mean mFI-5 0.82 ± 1.01 and CCI 4.18 ± 2.42. There was no association between increased frailty and 30-day medical or surgical outcomes (including postoperative cerebrospinal fluid leak), prolonged length of hospital stay, or mortality (all P > .05). Higher mFI-5 was associated with an increased risk for 30-day readmission (odds ratio: 2.35, 95% confidence Interval: 1.10-5.64, P = .04). CONCLUSION: Despite the patient population being notably frail, we only identified an increased risk for 30-day readmission and observed no links with deteriorating surgical, medical, or mortality outcomes. This implies that conventional frailty metrics may not effectively align with EEA outcomes.