JAMA otolaryngology-- head & neck surgery最新文献

Importance: Meniere disease accounts for up to 15% of new vestibular diagnoses,; however, the optimal treatment has yet to be identified. A conservative treatment that would reduce or stop the vertigo episodes has not been identified.

Objective: To determine the efficacy of a serotonin-norepinephrine reuptake inhibitor, venlafaxine, compared to placebo in treating patients with Meniere disease.

Design, setting, and participants: This was a randomized, double-blind, placebo-controlled, crossover pilot study spanning 22 weeks of follow-up. The clinical trial took place at a single-center tertiary referral center in Charleston, South Carolina. Participants were eligible if they were 18 years or older, had definite Meniere disease criteria as defined by Barany criteria, had at least 2 episodes in the last month, had not received intratympanic gentamycin, skull base surgery, or radiation therapy to the head or neck, not currently taking diuretics for Meniere disease, not currently taking oral steroids, and not currently taking serotonin-modulating medication. Patients were enrolled between February 2020 and September 2023.

Interventions: Patients received either 1 venlafaxine tablet, 37.5 mg, taken daily by mouth for 8 weeks or 1 placebo tablet taken daily by mouth for 8 weeks. Group 1 received placebo during phase 1 of the trial and venlafaxine in phase 2 of the trial. Group 2 received venlafaxine during phase 1 of the trial and placebo in phase 2 of the trial.

Main outcomes and measures: The main outcomes included the number of episodes and scores on the following scales: Dizziness Handicap Inventory, Neuropsychological Vertigo Inventory, Meniere Disease Patient-Oriented Symptom Index, 20-Item Short Form Health Survey, Penn State Worry Questionnaire, Cognitive Failure Questionnaire.

Results: A total of 182 patients were screened, and 40 participants with Meniere disease enrolled in the trial. The mean (SD) age of participants was 56.6 (14.3) years, and 22 (55%) were female. Participants had a mean (SD) of 13.8 (10.1) episodes per phase at baseline, 5.4 (4.4) episodes (Δ8.4) during the venlafaxine phase, and 5.0 (4.6) episodes (Δ8.8) during the placebo phase. No significant difference was identified between venlafaxine and placebo groups in the number of episodes or quality-of-life metrics.

Conclusions and relevance: This randomized clinical trial failed to identify a difference between venlafaxine and placebo in number of episodes and other quality-of-life metrics. Future studies may benefit from different dosing regimens, larger cohorts, and longer lengths of therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT04218123.

Importance: Current medical therapies in idiopathic subglottic stenosis (iSGS) are insufficient in preventing the development and progression of scar tissue. An inhibitor of mammalian target of rapamycin, everolimus is an immunosuppressive medication shown to be effective in reducing fibrosis across a variety of fibroproliferative disorders, including preclinical models of iSGS.

Objective: To evaluate the effect of oral everolimus on postoperative recurrence of stenosis in iSGS.

Design, setting, and participants: This open-label, single-arm, phase 1, nonrandomized clinical trial analyzed 7 perimenopausal participants diagnosed with iSGS and followed-up at a tertiary care academic center for 6 months after dilation surgery. The trial was conducted from November 1, 2022, through May 15, 2024.

Intervention: Participants took a 1.5-mg daily oral dose of everolimus for 42 days after surgery.

Main outcomes and measures: The primary outcome measure was safety as determined by adverse events. Secondary outcome measures included change in peak expiratory flow from baseline through 180 days after surgery; change in the luminal area, measured by computed tomographic (CT) scan, from the 14th and the 180th day; and changes in quality-of-life scores.

Results: Of the 8 perimenopausal participants, 7 (median age, 50 years [IQR, 45.0-52.5 years]) completed the study. Compared with baseline at all time points, there was an increase in peak expiratory flow. The median difference in liters per minute was 125 (95% CI, 90-270) on day 7 after surgery; 150 (95% CI, 110-290) on day 14; 138 (95% CI, 116-280) on day 28; 160 (95% CI, 100-270) on day 42; 155 (95% CI, 110-270) on day 60; 140 (95% CI, 100-270) on day 90; and 100 (95% CI, 20-240) on day 180. A decrease in the CT luminal area was observed from the day-14 measure to the day-180 measure (median stenosis, 7.2%; IQR, 1.9%-15.4%). During the trial, 1 participant (14.3%) each developed oral ulcers, a urinary tract infection, and a skin infection.

Conclusions and relevance: In this interventional nonrandomized clinical trial of iSGS, adjuvant everolimus was well-tolerated with minor adverse events. Participants sustained postdilation peak expiratory flow for 13 weeks. These results support proceeding to a phase 2 trial to study drug efficacy and a more detailed investigation of adverse effects.

Trial registration: ClinicalTrials.gov Identifier: NCT05153668.

Importance: The eighth edition tumor, node, metastasis (TNM) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) is a poor predictor of survival in patients with lymph node metastases, possibly due to the inclusion of extranodal extension (ENE).

Objective: To identify the key determinants of prognosis in patients with nodal metastatic HNcSCC and analyze the association of ENE with TNM stage and investigate for prognostic heterogeneity in ENE-positive disease.

Design, setting, and participants: This retrospective, multicenter cohort study was conducted at 4 Australian tertiary referral centers using prospectively collected data in patients treated between 1980 and 2017 with a median (IQR) follow-up of 3.2 (3.9) years. The study population included 1309 consecutive patients with HNcSCC that was metastatic to parotid and/or cervical nodes. After excluding cases with perioperative mortality, missing data, or follow-up, the final study population included 1151 patients.

Exposure: Curative intent surgery ± adjuvant radiotherapy.

Main outcomes and measures: Differences in locoregional control (LRC), disease-specific survival (DSS), and overall survival were determined using Cox regression analysis.

Results: Among 1151 patients, 976 (84.8%) were male and 175 (15.2%) female, with a median age of 73.3 years (range, 18-100 years). On multivariable analysis, immunosuppression (hazard ratio [HR], 2.48; 95% CI, 1.64-3.74), perineural invasion (HR, 1.69; 95% CI, 1.25-2.30), ENE (HR, 1.53; 95% CI, 0.95-2.44), size (>3-6 cm vs ≤3 cm [HR, 1.41; 95% CI, 1.03-1.93]; >6 cm vs ≤3 cm [HR, 5.01; 95% CI, 2.98-8.42]), and number of nodal metastases (3-4 vs 1-2 [HR, 1.54; 95% CI, 1.01-2.34]; ≥5 vs 1-2 [HR, 2.86; 95% CI, 1.99-4.11]) were associated with DSS. Similar results were found for LRC and overall survival. More than 90% of the population was categorized as TNM stage IV, with 32% attributable to ENE. In the ENE-positive subset (n = 860), DSS ranged from 8% to 88% based on stratification using other clinicopathological factors.

Conclusions and relevance: The study results suggest that immunosuppression, perineural invasion, ENE, and size and number of nodal metastases are associated with reduced survival and LRC in HNcSCC with nodal metastases. The inclusion of ENE in HNcSCC staging needs to be reassessed, as it ascribes excessive importance to ENE and upstages most patients to TNM stage IV, despite many having a high chance of cure.