ABSTRACT
PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of mesenchymal sinonasal tract tumors (STTs), a distinct subset of STTs. Despite their rarity, mesenchymal STTs represent a unique clinical challenge, characterized by their rarity, often slow progression, and frequently subtle or overlooked symptoms. The complex anatomy of the sinonasal area, which includes critical structures such as the orbit, brain, and cranial nerves, further complicates surgical treatment options. This underscores an urgent need for more advanced and specialized therapeutic approaches. RECENT FINDINGS: Advancements in molecular diagnostics, particularly in next-generation sequencing, have significantly enhanced our understanding of STTs. Consequently, the World Health Organization has updated its tumor classification to better reflect the distinct histological and molecular profiles of these tumors, as well as to categorize mesenchymal STTs with greater accuracy. The growing understanding of the molecular characteristics of mesenchymal STTs opens new possibilities for targeted therapeutic interventions, marking a significant shift in treatment paradigms. This review article concentrates on mesenchymal STTs, specifically addressing sinonasal tract angiofibroma, sinonasal glomangiopericytoma, biphenotypic sinonasal sarcoma, and skull base chordoma. These entities are marked by unique histopathological and molecular features, which challenge conventional treatment approaches and simultaneously open avenues for novel targeted therapies. Our discussion is geared towards delineating the molecular underpinnings of mesenchymal STTs, with the objective of enhancing therapeutic strategies and addressing the existing shortcomings in the management of these intricate tumors.
Subject(s)
Paranasal Sinus Neoplasms , Paranasal Sinuses , Sarcoma , Humans , Paranasal Sinuses/pathology , Paranasal Sinus Neoplasms/drug therapy , Paranasal Sinus Neoplasms/pathology , Sarcoma/pathologyABSTRACT
INTRODUCTION: Sialendoscopy is a minimally invasive technique for the management of salivary gland disease. This work characterizes its utility for treating chronic sialadenitis due to Sjogren's syndrome and radioactive iodine (RAI) therapy. METHODS: A single-center, retrospective review of patients undergoing sialendoscopy between March 2013 and May 2019 for the treatment of chronic sialadenitis due to Sjogren's or prior RAI therapy was performed. RESULTS: Thirty-four patients with Sjogren's and 25 patients who received RAI were identified, undergoing a total of 86 procedures. Median age at presentation was 53 years with mean follow-up time of 14.3 months. Seventy-two procedures were performed on the parotid gland, four on the submandibular gland, and ten on both glands. Corticosteroid injection and duct dilation were performed most commonly. Sixteen patients required repeat procedure. All patients were symptomatically improved at follow-up visit. DISCUSSION/CONCLUSION: These results support the idea that sialendoscopy offers symptomatic benefit for patients with chronic sialadenitis due to Sjogren's or RAI.
Subject(s)
Sialadenitis , Sjogren's Syndrome , Thyroid Neoplasms , Humans , Middle Aged , Sjogren's Syndrome/complications , Sjogren's Syndrome/radiotherapy , Sjogren's Syndrome/chemically induced , Iodine Radioisotopes/therapeutic use , Endoscopy/methods , Thyroid Neoplasms/surgery , Sialadenitis/etiology , Sialadenitis/surgery , Chronic DiseaseABSTRACT
Background: Aspirin therapy and/or type 2 (T2) biologics are used in the management of aspirin-exacerbated respiratory disease (AERD). Objective: To identify the number of patients with AERD who tolerated aspirin therapy, yet due to persistent symptoms, incorporated T2 biologic management. Methods: A retrospective review was performed between July 2016 and June 2019. Patients with AERD and who underwent endoscopic sinus surgery (ESS), aspirin desensitization (AD), and at least 6 months of aspirin therapy (ATAD) after AD, and who remained biologic-naive up through this timepoint were included in the study. Introduction of a T2 biologic while on ATAD was the primary outcome. The secondary outcome was a change in a validated patient-reported outcome measure for chronic rhinosinusitis score between the postoperative predesensitization timepoint, and the 6-month postdesensitization timepoint, presented as means and compared by using the Student's t-test. Results: A total of 103 patients met inclusion criteria. Two patients (1.9%) ultimately supplemented ATAD with a T2 biologic. The mean outcomes measure test score after 6 months of ATAD for patients who received biologics was 40.5 versus 15 in those who did not receive biologics (p = 0.02). The mean differences between the postoperative predesensitization test score and the 6-month postdesensitization test score for patients who went on to receive biologics was an increase of 13 versus a decrease of 10 for those patients who did not receive biologics (p = 0.12). Conclusion: ESS, coupled with AD and ATAD, was successful in the long-term management of the majority of the patients with AERD, which rarely required the incorporation of T2 biologics. Patient questionnaires, such as outcomes measure test score, may identify aspirin therapy failures and help guide the practitioner in deciding when to introduce T2 biologics into the patient's treatment regimen.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspirin/administration & dosage , Asthma, Aspirin-Induced/therapy , Biological Products/therapeutic use , Desensitization, Immunologic , Endoscopy , Nasal Surgical Procedures , Paranasal Sinuses/surgery , Adult , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/immunology , Aspirin/adverse effects , Aspirin/immunology , Asthma, Aspirin-Induced/diagnosis , Asthma, Aspirin-Induced/immunology , Biological Products/adverse effects , Combined Modality Therapy , Desensitization, Immunologic/adverse effects , Endoscopy/adverse effects , Female , Humans , Immune Tolerance , Male , Middle Aged , Nasal Surgical Procedures/adverse effects , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
The novel coronavirus (SARS-CoV-2) pandemic has influenced the timeliness of care for patients with both common and rare conditions, particularly those affecting high-risk operative sites such as the upper aerodigestive tract. Sinonasal undifferentiated carcinoma (SNUC) represents a rare malignancy of the sinonasal tract, a unique subset of which has never been previously reported in the otolaryngology literature and is characterized by inactivation of the SMARCB (INI-1) tumor suppressor gene. This subtype exhibits a particularly poor prognosis and is characterized pathologically by its rhabdoid appearance. Here we present the case of an individual who was diagnosed with a sinonasal mass during the SARS-CoV-2 pandemic, which was ultimately found to be SMARCB (INI-1)-deficient sinonasal carcinoma. Advanced imaging was deferred in the interest of limiting the patient's exposure to the virus, and expedited operative management was performed which facilitated prompt referral for adjuvant chemoradiation. The SARS-CoV-2 pandemic presents unique challenges, but the work-up of high-risk lesions must be prioritized; this continues to be paramount as SARS-CoV-2 resurges in many cities across the USA.
Subject(s)
COVID-19/epidemiology , Carcinoma/diagnosis , Carcinoma/surgery , Maxillary Sinus Neoplasms/diagnosis , Maxillary Sinus Neoplasms/surgery , Biopsy , Carcinoma/pathology , Chemoradiotherapy, Adjuvant , Diagnosis, Differential , Endoscopy , Female , Humans , Maxillary Sinus Neoplasms/pathology , Middle Aged , SARS-CoV-2 , Tomography, X-Ray ComputedABSTRACT
TAS2R38 is a human bitter receptor gene with a common but inactive allele; people homozygous for the inactive form cannot perceive low concentrations of certain bitter compounds. The frequency of the inactive and active forms of this receptor is nearly equal in many human populations, and heterozygotes with 1 copy of the active form and 1 copy of the inactive form have the most common diplotype. However, even though they have the same genotype, heterozygotes differ markedly in their perception of bitterness, perhaps in part because of differences in TAS2R38 mRNA expression. Other tissues express this receptor too, including the nasal sinuses, where it contributes to pathogen defense. We, therefore, wondered whether heterozygous people had a similar wide range of TAS2R38 mRNA in sinonasal tissue and whether those with higher TAS2R38 mRNA expression in taste tissue were similarly high expressers in nasal tissue. To that end, we measured gene expression by quantitative PCR in taste and sinonasal tissue and found that expression abundance in one tissue was not related to the other. We confirmed the independence of expression in other tissue pairs expressing TAS2R38 mRNA, such as pancreas and small intestine, using autopsy data from the Genotype-Tissue Expression project (although people with high expression of TAS2R38 mRNA in colon also tended to have higher expression in the small intestine). Thus, taste tissue TAS2R38 mRNA expression among heterozygotes is unlikely to predict expression in other tissues, perhaps reflecting tissue-dependent function, and hence regulation, of this protein.
Subject(s)
RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/metabolism , Adult , Alleles , Female , Gene Expression , Genotype , Heterozygote , Humans , Male , Nasal Cavity/metabolism , Polymorphism, Single Nucleotide , Receptors, G-Protein-Coupled/genetics , Taste/physiology , Tongue/metabolismABSTRACT
BACKGROUND/AIMS: Sialendoscopy has as yet been shown to be ideal for the management of sialolithiasis and chronic inflammatory diseases of the salivary gland. However, its applicability to the management of a broad range of salivary gland disease is continually growing. METHODS: Here we present a case report where sialendoscopy was used to successfully manage an intraparenchymal submandibular gland abscess in a patient with oropharyngeal squamous cell carcinoma managed with primary chemoradiation. RESULTS: The use of sialendoscopy enabled visualization of the patency of salivary ducts, drainage of abscess, and irrigation of antibiotic-impregnated fluid. In this particular patient, we were able to avoid a transcervical approach through a previously irradiated field, which would have necessitated concurrent tracheostomy and placed undue risk to surrounding neurovascular structures. CONCLUSION: Sialendoscopy should thus, in select patients, be considered as an initial intervention for patients with intraparenchymal salivary gland abscesses in which prior therapy creates an increased risk of complication from an open transcervical approach.
Subject(s)
Abscess/therapy , Endoscopy , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/therapy , Submandibular Gland Diseases/therapy , Abscess/etiology , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/radiotherapy , Drainage/methods , Endoscopy/methods , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/complications , Oropharyngeal Neoplasms/radiotherapy , Sialadenitis/therapy , Submandibular Gland/diagnostic imaging , Submandibular Gland Diseases/diagnostic imaging , Submandibular Gland Diseases/etiology , Tomography, X-Ray ComputedABSTRACT
We investigated whether the abundance of bitter receptor mRNA expression from human taste papillae is related to an individual's perceptual ratings of bitter intensity and habitual intake of bitter drinks. Ratings of the bitterness of caffeine and quinine and three other bitter stimuli (urea, propylthiouracil, and denatonium benzoate) were compared with relative taste papilla mRNA abundance of bitter receptors that respond to the corresponding bitter stimuli in cell-based assays ( TAS2R4, TAS2R10, TAS2R38, TAS2R43, and TAS2R46). We calculated caffeine and quinine intake from a food frequency questionnaire. The bitterness of caffeine was related to the abundance of the combined mRNA expression of these known receptors, r = 0.47, p = .05, and self-reported daily caffeine intake, t(18) = 2.78, p = .012. The results of linear modeling indicated that 47% of the variance among subjects in the rating of caffeine bitterness was accounted for by these two factors (habitual caffeine intake and taste receptor mRNA abundance). We observed no such relationships for quinine but consumption of its primary dietary form (tonic water) was uncommon. Overall, diet and TAS2R gene expression in taste papillae are related to individual differences in caffeine perception.
Subject(s)
Caffeine/pharmacology , Quinine/pharmacology , RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/physiology , Taste Perception/drug effects , Taste Perception/physiology , Adult , DNA Copy Number Variations , Feeding Behavior , Female , Gene Expression/drug effects , Humans , Male , Propylthiouracil/pharmacology , Quaternary Ammonium Compounds/pharmacology , Taste Buds/metabolism , Urea/pharmacology , Young AdultABSTRACT
The bitter taste receptor T2R38 has been shown to play a role in the pathogenesis of chronic rhinosinusitis (CRS), where the receptor functions to enhance upper respiratory innate immunity through a triad of beneficial immune responses. Individuals with a functional version of T2R38 are tasters for the bitter compound phenylthiocarbamide (PTC) and exhibit an anti-microbial response in the upper airway to certain invading pathogens, while those individuals with a non-functional version of the receptor are PTC non-tasters and lack this beneficial response. The clinical ramifications are significant, with the non-taster genotype being an independent risk factor for CRS requiring surgery, poor quality-of-life (QOL) improvements post-operatively, and decreased rhinologic QOL in patients with cystic fibrosis. Furthermore, indirect evidence suggests that non-tasters also have a larger burden of biofilm formation. This new data may influence the clinical management of patients with infectious conditions affecting the upper respiratory tract and possibly at other mucosal sites throughout the body.
Subject(s)
Immunity, Innate , Paranasal Sinuses/immunology , Respiratory Tract Diseases/immunology , Taste Buds/metabolism , Animals , Biofilms , Genetic Variation , Humans , Respiratory Tract Diseases/geneticsABSTRACT
Odontogenic sinusitis (ODS) is a common cause of orbital, intracranial, and osseous infectious extrasinus complications. Dental infections can spread to the orbital or intracranial spaces though the sinuses via thrombophlebitis or direct extension, or from the dentition or oral cavity via vascular channels in the maxillary alveolar bone. ODS typically presents with unilateral involvement both clinically and radiographically. Any suspicion for extrasinus spread based on history and physical examination should be followed by appropriate imaging, formal dental evaluation, and, when appropriate, ophthalmology and neurosurgery consultations. This multidisciplinary approach ensures appropriate management of both the acute orbital and intracranial complications.
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The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence for technical factors that optimize outcomes in skull base reconstruction following endoscopic skull base surgery for intradural pathologies. These topics include the use of free mucosal grafts versus vascularized pedicled nasoseptal flaps; the use of autologous versus synthetic grafts; and the roles of lumbar drains, dural sealants, and nasal packing. This EPS was developed following the recommended methodology and approval process as previously outlined. As there are a myriad of techniques and limited agreement on the accepted principles of skull base reconstruction, this EPS aims to summarize the existing evidence and provide clinically meaningful guidance on these divergent practices. Following a modified Delphi approach, five statements were developed, four of which reached consensus and one of which reached near consensus. These statements and the accompanying evidence are summarized along with an assessment of future needs.
Subject(s)
Endoscopy , Plastic Surgery Procedures , Skull Base , Humans , Endoscopy/methods , Plastic Surgery Procedures/methods , Skull Base/surgery , Societies, Medical , Surgical Flaps , United StatesABSTRACT
The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence regarding postoperative precautions for patients following endoscopic skull base surgery for intradural pathology. These topics include the administration of postoperative nasal hygiene; patient mobilization and activity level; the resumption of continuous positive airway pressure in patients with obstructive sleep apnea; and the timing and capacity with which a patient may be subjected to barotrauma, such as air travel postoperatively. This EPS was developed following the recommended methodology and approval process as previously outlined. Given the diverse practices and limited agreement on the accepted principles regarding postoperative precautions for patients following skull base surgery, this EPS seeks to summarize the existing literature and provide clinically relevant guidance to bring clarity to these differing practice patterns. Following a modified Delphi approach, four statements were developed, all of which reached consensus. Because of the paucity of literature on these topics, these statements represent a summation of the limited literature and the experts' opinions. These statements and the accompanying evidence are summarized below, along with an assessment of future needs.
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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
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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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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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
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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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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BACKGROUND: Ketamine is a commonly used anesthetic, but the mechanistic basis for its clinically relevant actions remains to be determined. The authors previously showed that HCN1 channels are inhibited by ketamine and demonstrated that global HCN1 knockout mice are twofold less sensitive to hypnotic actions of ketamine. Although that work identified HCN1 channels as a viable molecular target for ketamine, it did not determine the relevant neural substrate. METHODS: To localize the brain region responsible for HCN1-mediated hypnotic actions of ketamine, the authors used a conditional knockout strategy to delete HCN1 channels selectively in excitatory cells of the mouse forebrain. A combination of molecular, immunohistochemical, and cellular electrophysiologic approaches was used to verify conditional HCN1 deletion; a loss-of-righting reflex assay served to ascertain effects of forebrain HCN1 channel ablation on hypnotic actions of ketamine. RESULTS: In conditional knockout mice, HCN1 channels were selectively deleted in cortex and hippocampus, with expression retained in cerebellum. In cortical pyramidal neurons from forebrain-selective HCN1 knockout mice, effects of ketamine on HCN1-dependent membrane properties were absent; notably, ketamine was unable to evoke membrane hyperpolarization or enhance synaptic inputs. Finally, the EC50 for ketamine-induced loss-of-righting reflex was shifted to significantly higher concentrations (by approximately 31%). CONCLUSIONS: These data indicate that forebrain principal cells represent a relevant neural substrate for HCN1-mediated hypnotic actions of ketamine. The authors suggest that ketamine inhibition of HCN1 shifts cortical neuron electroresponsive properties to contribute to ketamine-induced hypnosis.
Subject(s)
Analgesics/pharmacology , Cyclic Nucleotide-Gated Cation Channels , Hypnotics and Sedatives/pharmacology , Ketamine/pharmacology , Potassium Channels , Prosencephalon/drug effects , Animals , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels , Mice , Mice, TransgenicABSTRACT
BACKGROUND: Postoperative nausea and vomiting (PONV) are adverse effects after surgery, which may increase the risk of complications. Aprepitant is a neurokinin-1 receptor blocker and has been shown to reduce chemotherapy-related nausea and vomiting and PONV. However, its role in endoscopic skull base surgery remains unclear. The purpose of this study was to evaluate the effect of aprepitant in reducing PONV in endoscopic transsphenoidal (TSA) pituitary surgery. METHODS: A retrospective chart review between July 2021 and January 2023 of 127 consecutive patients who underwent TSA was performed at a tertiary academic institution. Patients were divided into 2 groups based on preoperative aprepitant use. Two groups were matched based on known risk factors of PONV (age, sex, nonsmoking, and history of PONV). The primary outcome was the incidence of PONV. Secondary outcome measures included the number of anti-emetic use, length of stay, and postoperative cererebrospinal fluid (CSF) leak. RESULTS: After matching, 48 patients were included in each group. The aprepitant group demonstrated a significantly lower incidence of vomiting than the non-aprepitant group (2.1% vs 22.9%, p = 0.002). The number of nausea episodes and anti-emetic use decreased with aprepitant use (p < 0.05). There was no difference in the incidence of nausea, length of stay, or postoperative CSF leak. Multivariate analysis demonstrated that aprepitant decreased the incidence of postoperative vomiting with odds ratio of 0.107. CONCLUSION: Aprepitant may serve as a useful preoperative treatment to reduce PONV in patients undergoing TSA. Further studies are needed to evaluate its impact in other arenas of endoscopic skull base surgery.
Subject(s)
Antiemetics , Pituitary Diseases , Humans , Aprepitant/therapeutic use , Postoperative Nausea and Vomiting/epidemiology , Postoperative Nausea and Vomiting/prevention & control , Postoperative Nausea and Vomiting/chemically induced , Antiemetics/therapeutic use , Retrospective Studies , Morpholines/therapeutic useABSTRACT
KEY POINTS: Patients are increasingly turning to online education materials to aid with disease management. Patient education materials on aspirin-exacerbated respiratory disease are of poor readability with significant room for improvement.