Citations

Background and Purpose— Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection. Methods— In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type. Results— For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23–0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites. Conclusions— Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02089217.

Background Endoscopic endonasal resection (EER) of sinonasal mucosal melanoma (SMM) is a newer surgical alternative to traditional external and/or open resection (OR). Studies on long-term outcomes are necessary to validate EER for this aggressive sinonasal malignancy. Objective To compare outcomes of EER versus OR in SMM. Methods A case series of patients who underwent surgical resection of SMM at a tertiary-care institution (2000–2015) was studied retrospectively. Demographics, tumor site and stage, surgical approach, surgical margin status, local control, and survival were compared between those who underwent EER and OR. Results Twenty-two patients met inclusion criteria. Nine underwent EER and 13 underwent OR. The mean age in the EER and OR groups was similar, 78.7 and 72.3 years, respectively. Two-thirds of patients were women (EER, 66.7%; OR, 61.5%). The nasal cavity was the most common primary tumor site (EER, 77.8%; OR, 84.6%). The local tumor stage in both groups was similar, with the majority of cases being T4 (EER, 55.6%; OR, 61.5%; p = 0.99). Negative margins were achieved in all EERs and in 69.2% of ORs. Median follow-up was 25.0 months for the overall group (range, 1.7–172.9 months), 32.6 months (range, 3.4–58.7 months) for EER and 14.1 months (range, 1.7–172.9 months) for OR cohorts. The 5-year overall survival was statistically similar in both groups (EER, 53.3%; OR, 22.7%; p = 0.214) as was disease-free survival (EER, 55.6%; OR, 22.8%; p = 0.178). Local control, however, was significantly higher in the EER cohort (EER, 85.7%; OR, 37.6%; p = 0.026). Conclusion In carefully selected patients with sinonasal melanoma, endoscopic surgery with an experienced team may offer comparable survival and improved local control over open surgery. Prospective, multicentered studies with larger cohorts are needed to validate these results.

Background The role of microbiota in sinonasal inflammation can be further understood by targeted sampling of healthy and diseased subjects. We compared the microbiota of the middle meatus (MM) and inferior meatus (IM) in healthy, allergic rhinitis (AR), and chronic rhinosinusitis (CRS) subjects to characterize intrasubject, intersubject, and intergroup differences. Methods Subjects were recruited in the office, and characterized into healthy, AR, and CRS groups. Endoscopically‐guided swab samples were obtained from the MM and IM bilaterally. Bacterial microbiota were characterized by sequencing the V3‐V4 region of the 16S ribosomal RNA (rRNA) gene. Results Intersubject microbiome analyses were conducted in 65 subjects: 8 healthy, 11 AR, and 46 CRS (25 CRS with nasal polyps [CRSwNP]; 21 CRS without nasal polyps [CRSsNP]). Intrasubject analyses were conducted for 48 individuals (4 controls, 11 AR, 8 CRSwNP, and 15 CRSwNP). There was considerable intersubject microbiota variability, but intrasubject profiles were similar ( p = 0.001, nonparametric t test). Intrasubject bacterial diversity was significantly reduced in MM of CRSsNP subjects compared to IM samples ( p = 0.022, nonparametric t test). CRSsNP MM samples were enriched in Streptococcus , Haemophilus , and Fusobacterium spp. but exhibited loss of diversity compared to healthy, CRSwNP, and AR subject‐samples ( p < 0.05; nonparametric t test). CRSwNP patients were enriched in Staphylococcus , Alloiococcus , and Corynebacterium spp. Conclusion This study presents the sinonasal microbiome profile in one of the larger populations of non‐CRS and CRS subjects, and is the first office‐based cohort in the literature. In contrast to healthy, AR, and CRSwNP subjects, CRSsNP MM samples exhibited decreased microbiome diversity and anaerobic enrichment. CRSsNP MM samples had reduced diversity compared to same‐subject IM samples, a novel finding.

Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration United States National Institutes of Health Clinicaltrials.gov NCT02089217

ObjectiveCompare nasal endoscopy with 3 mm versus conventional 4 mm rigid 30° endoscopes for visualization, patient comfort, and examiner ease.MethodsTen adults with no previous sinus surgery underwent bilateral nasal endoscopy with both 4 mm and 3 mm endoscopes (resulting in 20 paired nasal endoscopies). Visualization, patient discomfort and examiner's difficulty were assessed with every endoscopy. Sino‐nasal structures were checked on a list if visualized satisfactorily. Patients rated discomfort on a standardized numerical pain scale (0–10). Examiners rated difficulty of examination on a scale of 1–5 (1 = easiest).ResultsVisualization with 3 mm endoscope was superior for the sphenoid ostium (P = 0.002), superior turbinate (P = 0.007), spheno‐ethmoid recess (P = 0.006), uncinate process (P = 0.002), cribriform area (P = 0.007), and Valve of Hasner (P = 0.002). Patient discomfort was not significantly different for 3 mm vs. 4 mm endoscopes but correlated with the examiners' assessment of difficulty (r = 0.73). The examiner rated endoscopy with 4 mm endoscopes more difficult (P = 0.027).ConclusionsThe 3 mm endoscope was superior in visualizing the sphenoid ostium, superior turbinate, spheno‐ethmoid recess, uncinate process, cribriform plate, and valve of Hasner. It therefore may be useful in assessment of spheno‐ethmoid recess, nasolacrimal duct, and cribriform area pathologies. Overall, patients tolerated nasal endoscopy well. Though patient discomfort was not significantly different between the endoscopes, most discomfort with 3 mm endoscopes was noted while examining structures difficult to visualize with the 4 mm endoscope. Patients' discomfort correlated with the examiner's assessment of difficulty.

Chest wall strapping has been used to assess mechanisms of dyspnea with restrictive lung disease. This study examined the hypothesis that dyspnea with restriction depends principally on the degree of reflex ventilatory stimulation. We compared dyspnea at the same (iso)ventilation when added dead space provided a component of the ventilatory stimulus during exercise. Eleven healthy men undertook a randomized controlled crossover trial that compared four constant work exercise conditions: 1) control (CTRL): unrestricted breathing at 90% gas exchange threshold (GET); 2) CTRL+dead space (DS): unrestricted breathing with 0.6-l dead space, at isoventilation to CTRL due to reduced exercise intensity; 3) CWS: chest wall strapping at 90% GET; and 4) CWS+DS: chest strapping with 0.6-l dead space, at isoventilation to CWS with reduced exercise intensity. Chest strapping reduced forced vital capacity by 30.4 ± 2.2% (mean ± SE). Dyspnea at isoventilation was unchanged with CTRL+DS compared with CTRL (1.93 ± 0.49 and 2.17 ± 0.43, 0–10 numeric rating scale, respectively; P = 0.244). Dyspnea was lower with CWS+DS compared with CWS (3.40 ± 0.52 and 4.51 ± 0.53, respectively; P = 0.003). Perceived leg fatigue was reduced with CTRL+DS compared with CTRL (2.36 ± 0.48 and 2.86 ± 0.59, respectively; P = 0.049) and lower with CWS+DS compared with CWS (1.86 ± 0.30 and 4.00 ± 0.79, respectively; P = 0.006). With unrestricted breathing, dead space did not change dyspnea at isoventilation, suggesting that dyspnea does not depend on the mode of reflex ventilatory stimulation in healthy individuals. With chest strapping, dead space presented a less potent stimulus to dyspnea, raising the possibility that leg muscle work contributes to dyspnea perception independent of the ventilatory stimulus. NEW & NOTEWORTHY Chest wall strapping was applied to healthy humans to simulate restrictive lung disease. With chest wall strapping, dyspnea was reduced when dead space substituted for part of a constant exercise stimulus to ventilation. Dyspnea associated with chest wall strapping depended on the contribution of leg muscle work to ventilatory stimulation. Chest wall strapping might not be a clinically relevant model to determine whether an alternative reflex ventilatory stimulus mimics the intensity of exertional dyspnea.