A 22-year single institution review of 119 cases of salivary duct carcinoma.

Objective: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. Methods: This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. Results: This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p<.001), distant metastasis (p<.001), perineural invasion (p = .027), and lymphovascular invasion (p = .018) were predictive of decreased OS and DSS. Trastuzumab administration was not associated with survival in HER-2-positive patients receiving chemotherapy. Multivariate analyses demonstrated that presence of nodal disease (HR 30.337, 95% CI 2.782-330.851, p = .005) and carcinoma ex pleomorphic adenoma (HR 5.54, 95% CI 1.024-29.933, p = .047) were associated with decreased OS. Conclusion: Our patients had more favorable survival rates compared to prior studies, which may be due to lower incidence of nodal disease. Factors associated with worse survival included nodal and distant metastases, perineural invasion, lymphovascular invasion, and tumor size. Level of Evidence: Level 3.

Patient perspectives on chronic rhinosinusitis in cystic fibrosis: Symptom prioritization in the era of highly effective modulator therapy.

BACKGROUND: Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied. METHODS: Adult PwCF + CRS were enrolled at eight centers into a prospective, observational study (2019-2023). Participants were administered the 22-SinoNasal Outcome Test (SNOT-22) survey and a modified SNOT-22 instrument examining symptom importance. We determined importance rankings for individual symptoms and SNOT-22 symptom importance subdomains in two sets of subgroups-those pursuing ESS versus continuing medical management (CMT), and those on elexacaftor/tezacaftor/ivacaftor (ETI) versus not on ETI. RESULTS: Among 69 participants, the highest priorities were nasal congestion (n = 48, 69.6% important), post-nasal discharge (32, 46.4%), facial pain (29, 43.3%), waking up tired (27, 39.1%), and fatigue (26, 37.7%). Those electing surgery (n = 23) prioritized sleep and psychological dysfunction symptoms compared to those pursuing CMT (n = 49) (sleep median score = 19.0 [interquartile range: 12.0, 25.0] vs. 4.5 [0.0, 12.8]; p < 0.0001; psychological = 17.0 [7.0, 26.0] vs. 7.0 [0.0, 15.8]; p = 0.002). ETI users had comparable SNOT-22 total symptom importance scores to non-ETI users (p = 0.14). Non-ETI users (n = 34) showed a trend toward prioritizing sleep symptoms compared to ETI users (n = 35) (13.0 [2.8, 22.3] vs. 6.0 [2.0, 17.0]; p = 0.055). CONCLUSIONS: Nasal congestion and post-nasal discharge were top priorities reported by PwCF + CRS. Those electing surgery prioritized sleep and psychological symptoms, highlighting their importance in pre-operative discussions. Non-ETI users' prioritization of sleep improvement may highlight their unique disease impact and therapeutic needs; however, additional investigation is required.

Factors that predict pursuing sinus surgery in the era of highly effective modulator therapy.

BACKGROUND: Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality-of-life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied. METHODS: Adult PwCF + CRS were enrolled into a prospective, observational, multi-institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS. RESULTS: Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT-22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire-9-Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire-Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p < 0.050). Multivariable regression identified that worse SNOT-22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.16, p = 0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004-0.34, p = 0.004) was associated with pursing medical therapy. CONCLUSIONS: Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden.

Decreases in Rhinology Care Utilization by People with Cystic Fibrosis on Highly Effective Modulator Therapy.

BACKGROUND: Many people with cystic fibrosis (PwCF) have chronic rhinosinusitis (CRS). CRS requires additional management beyond that of pulmonary disease and leads to increased utilization of healthcare resources. Elexacaftor/tezacaftor/ivacaftor (ETI) is a highly effective modulator therapy that has been shown to improve CRS in PwCF. However, the impact of ETI on rhinologic healthcare utilization is understudied. OBJECTIVE: To compare rates of rhinologic healthcare utilization and procedures among PwCF prior to and after initiating ETI therapy. METHODS: A single-center, cohort study investigating adult PwCF was performed in January 2023. Demographics, clinical characteristics, and data related to CF treatment were retrospectively abstracted. Characteristics of the cohort were compared over 2 periods: the 12-months prior to ETI initiation and the 12-months after ETI initiation. Post-ETI data were linearly extrapolated if a subject had not yet completed the full 12 months of ETI. Paired t-testing, Wilcoxon signed rank testing, and regression analysis were performed. RESULTS: Of 126 PwCF, 98 (77.8%) were on ETI therapy and 35 (27.7%) were both on ETI and concurrently followed by the rhinology service (ETI-ENT). Rhinology clinic visits (P = .007) and frequency of obtaining nasal cultures (P = .046) decreased for the ETI-ENT cohort after initiating ETI treatment. There were no significant changes in the number of endoscopic sinus surgeries (P = .452) performed. Beyond ETI use, regression analysis did not identify any factors associated with changes in utilization. CONCLUSION: Aspects of rhinology healthcare utilization by PwCF decreased after initiation of ETI therapy. Additional studies are needed to determine rhinologic healthcare requirements for PwCF who remain on ETI for the long-term and to evaluate larger cohorts of PwCF on ETI.

Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy.

INTRODUCTION: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory-specific quality-of-life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. METHODS: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution-based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. RESULTS: Of 129 PwCF included, 65 had QOD scores before and 3-6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was -1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). CONCLUSION: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner.

Gender Disparities in Stroke Code Activation in Patients with Intracerebral Hemorrhage.

OBJECTIVES: Routine implementation of protocol-driven stroke "codes" results in timelier and more effective acute stroke management. However, it is unclear if patient demographics contribute to disparities in stroke code activation. We aimed to explore these demographic factors in a retrospective cohort study of patients with intracerebral hemorrhage (ICH). MATERIALS AND METHODS: We identified consecutive patients with non-traumatic ICH who presented directly to our Comprehensive Stroke Center over 2 years and collected data on demographics, clinical features, and stroke code activation. We used multivariable logistic regression to examine differences in stroke code activation based on patient demographics while adjusting for initial clinical features (NIH Stroke Scale, FAST [facial drooping, arm weakness, speech difficulties] vs. non-FAST symptoms, time from last-known-well [LKW], and systolic blood pressure [SBP]). RESULTS: Among 265 patients, 68% (n=179) had a stroke code activation. Stroke codes occurred less frequently in women (62%) than men (72%) and in non-white (57%) vs. white patients (70%). Non-stroke code patients were less likely to have FAST symptoms (37% vs. 87%) and had lower initial SBP (mean±SD 159.3±34.2 vs. 176.0±31.9 mmHg) than stroke code patients. In our primary multivariable models, neither age nor race were associated with stroke code activation. However, women were significantly less likely to have stroke codes than men (OR 0.49 [95% CI 0.24-0.98]), as were non-FAST symptoms (OR 0.11 [95% CI 0.05-0.22]). CONCLUSIONS: Our data suggest gender disparities in emergency stroke care that should prompt further investigations into potential systemic biases. Increased awareness of atypical stroke symptoms is also warranted.

Statewide Emergency Medical Services Protocols for Status Epilepticus Management.

Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n = 3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first- and second-line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604-609.