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We conclude that nSMase2 is an important mediator in endothelial cells supporting transendothelial migration, which may be targeted by Tregs to reduce T-cell migration into tumors.

To evaluate patients who become symptomatic from superior semicircular canal dehiscence (SSCD) following head trauma.

Case series assessing patients presenting with SSCD after a trauma.

A case series was completed assessing patients presenting with SSCD after trauma. Data from three academic medical centers were evaluated, including the following imaging, videonystagmography (VNG)/vestibular evoked myogenic potential (VEMP) testing, audiometric assessment, and surgical repair. Outcome measures included the following 1) Description of audio-vestibular symptoms, 2) mean pre- and post-operative pure tone average (PTA), word recognition score (WRS), and air bone gap (ABG).

A total of 14 patients were included; 86% were male. Approximately 43% were found to have bilateral SSCD on imaging, with 57% of patients pursuing surgical management. The most common presenting symptoms included pulsatile tinnitus (93%), autophony (79%), and hearing loss (64%). Approximately 36% of patients underwent VNG/VEMP testing, with 83.3% of those demonstrating abnormal results. The mean audiometric findings on the symptomatic side included an air-conduction PTA of 38.0 dB, bone-conduction PTA of 24.3 dB, WRS of 81%, and ABG of 17.9 dB. Among patients who underwent surgery (57%), there was no significant change in the air-conduction PTA, bone-conduction PTA, or WRS (P > .05). However, there was an improvement in the ABG (preoperative=22.8 dB versus postoperative=9.7 dB; P=.005).

Head trauma may be a potentiating event for SSCD syndrome. This study advances the hypothesis that these patients likely have underlying radiographic SSCD prior to their trauma, and a traumatic event increases in intra-vestibular or intracranial pressures, unmasking SSCD syndrome.

IV Laryngoscope, 2021.

IV Laryngoscope, 2021.

Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) aims at modifying epileptogenic networks to reduce seizure frequency. High-frequency oscillations (HFOs), spikes, and cross-rate are quantifiable epileptogenic biomarkers. In this study, we sought to evaluate, using SEEG signals recorded before and after thermocoagulation, whether a variation in these markers is related to the therapeutic effect of this procedure and to the outcome of surgery.

Interictal segments of SEEG signals were analyzed in 38 patients during presurgical evaluation. We used an automatized method to quantify the rate of spikes, rate of HFOs, and cross-rate (a measure combining spikes and HFOs) before and after thermocoagulation. We analyzed the differences both at an individual level with a surrogate approach and at a group level with analysis of variance. We then evaluated the correlation between these variations and the clinical response to RF-TC and to subsequent resective surgery.

After thermocoure and the outcome of resective surgery.

Quantified changes in the rate of spikes, rate of HFOs, and cross-rate can be observed after thermocoagulation, and the reduction of these markers correlates with a favorable clinical outcome after RF-TC and with successful resective surgery. This may suggest that interictal biomarker modifications after RF-TC can be clinically used to predict the effectiveness of the thermocoagulation procedure and the outcome of resective surgery.

Babesia microti has gained a foothold in Canada as tick vectors become established in broader geographic areas. B. microti infection is associated with mild or no symptoms in healthy individuals but is transfusion-transmissible and can be fatal in immunocompromised individuals. This is the first estimate of clinically significant transfusion-transmitted babesiosis (TTB) risk in Canada.

The proportion of B. microti-antibody (AB)/nucleic acid amplification test (NAT)-positive whole blood donations was estimated at 5.5% of the proportion of the general population with reported Lyme Disease (also tick-borne) based on US data. Monte Carlo simulation estimated the number and proportion of infectious red cell units for three scenarios base, localized incidence (risk in Manitoba only), and donor study informed (prevalence from donor data). The model simulated 1,029,800 donations repeated 100,000 times for each.

In the base scenario 0.5 (0.01, 1.75), B. microti-NAT-positive donations would be expected per year, with 0.08 (0, 0.38) recipients suffering clinically significant TTB (1 every 12.5 years). In the localized incidence scenario, there were 0.21(0, 0.7) B. microti-NAT-positive donations, with 0.04 (0, 0.14) recipient infections (about 1 every 25 years). In the donor study informed scenario, there were 4.6 (0.3, 15.8) B. Bcl-2 apoptosis pathway microti-NAT-positive donations expected, and 0.81 (0.05, 3.14) clinically significant TTB cases per year.

The likelihood of clinically relevant TTB is low. Testing would have very little utility in Canada at this time. Ongoing pathogen surveillance in tick vectors is important as B. microti prevalence appears to be slowly increasing in Canada.

The likelihood of clinically relevant TTB is low. Testing would have very little utility in Canada at this time. Ongoing pathogen surveillance in tick vectors is important as B. microti prevalence appears to be slowly increasing in Canada.

The Laryngopharyngeal Measure of Perceived Sensation (LUMP) is a recently validated patient-reported outcome measure (PROM) aimed at evaluating the symptom severity of patients with globus pharyngeus (GP). The objective of this study was to define the normative values for the LUMP questionnaire.

Prospectively collected, descriptive research/scale development.

The LUMP questionnaire was completed by 88 subjects. Individuals without throat-related symptoms such as dysphagia, dysphonia, or cough were provided LUMP. The results of the eight-item questionnaire were analyzed for standard error of the mean (SEM), mean, and standard deviation (SD).

Review of the 88 LUMP questionnaires elucidated a mean of 0.42 (SEM=0.10, SD=0.96) in the normative population. By gender, the female (n=50) mean was 0.24, SD=0.66, SEM=0.09; for males (n=38), the mean was 0.66, SD=1.21, SEM=0.20.

This study provides normative data for the LUMP, a recently established PROM useful in patients with GP. A LUMP score greater than or equal to 3 should be considered abnormal and warrants additional attention.

3 Laryngoscope, 2021.

3 Laryngoscope, 2021.Acumulation of oxidized membrane lipids ultimately results in ferroptotic cell death, which can be prevented by the selenoenzyme glutathione peroxidase 4 (Gpx4). In vivo conditions promoting ferroptosis and susceptible cell types are still poorly defined. In this study, we analyzed the conditional deletion of Gpx4 in mice specifically in the myeloid cell lineages. Surprisingly, development and maintenance of LysM+ macrophages and neutrophils, as well as CD11c+ monocyte-derived macrophages and dendritic cells were unaffected in the absence of Gpx4. Gpx4-deficient macrophages mounted an unaltered proinflammatory cytokine response including IL-1β production following stimulation with TLR ligands and activation of several inflammasomes. Accordingly, Gpx4fl/fl LysM-cre mice were protected from bacterial and protozoan infections. Despite having the capacity to differentiate to alternatively activated macrophages (AAM), these cells lacking Gpx4 triggered ferroptosis both in vitro and in vivo following IL-4 overexpression and nematode infection. Exposure to nitric oxide restored viability of Gpx4-deficient AAM, while inhibition of iNOS in proinflammatory macrophages had no effect. These data together suggest that activation cues of tissue macrophages determine sensitivity to lipid peroxidation and ferroptotic cell death.

Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute to persistent, viscous middle ear (ME) effusions, hearing loss, and potential for developmental delay. Extraesophageal reflux (EER), specifically pepsin, triggers inflammatory signaling in respiratory mucosa and is associated with OM. The objective of this study was to investigate the association of pepsin with ME inflammatory signaling and the outcomes and examine causality in vitro.

Cross-sectional study.

ME fluid (MEF) and preoperative audiometric data were collected from 30 pediatric subjects undergoing tympanostomy tube placement for recurrent OM or OM with effusion. MEF viscosity was characterized by the surgeon. Pepsin, inflammatory molecules, and mucin were assayed by enzyme-linked immunosorbent assay (ELISA). ME epithelial primary culture was exposed to 0.1 to 1 mg/ml pepsin at pH 5, 6, and 7 for 30 minutes, and cytokine expression was assayed via qPCR.

Pepsin was observed in the MEF of 77% of patients (range 71-2,734 ng/ml). Pepsin correlated with effusion viscosity, interleukins -6 and -8, neutrophil elastase, and mucin 5B (P< .05). Pepsin-negative MEF was more frequently absent of interleukin 8 or mucin 5B (P< .05). Weak acid was generally insufficient to elicit cytokine expression in ME cells in vitro, however, pepsin induced IL6, IL8, and TNF at pH 7 (P< .05) and weak acid (pH 6) facilitated a response at lower pepsin concentration.

Pepsin may contribute to inflammatory signaling, persistent viscous effusion, and poorer OM outcomes.

4 Laryngoscope, 2021.

4 Laryngoscope, 2021.

Olfactory neuroblastoma (ONB) is a rare sinonasal malignant neoplasm that is known to develop late recurrence. The aim of this study is to evaluate the long-term outcomes of patients with ONB and to determine the factors associated with prognosis.

Retrospective study.

A retrospective review of the medical records of 139 patients diagnosed with ONB at MD Anderson Cancer Center was performed between 1991 and 2016. Descriptive statistics were calculated, and Kaplan-Meier curves were utilized to assess survival.

Median follow-up time was 75 months. Overall, 129 patients (92.8%) had surgery as part of their treatment and 82 (58.9%) patients received postoperative radiation therapy (PORT) or concurrent chemoradiotherapy. Endoscopic approaches were utilized for 72 patients, 69.4% of whom had pure endoscopic endonasal approaches. Five-year overall survival and disease-specific survival were 85.6% and 93.4%, respectively. Recurrence rate was 39.6% with a median time to recurrence of 42 months. Among the 31 patients who received elective nodal irradiation (ENI), two patients developed neck recurrence (6.4%) compared with 20 who developed neck recurrence when ENI was omitted (34.4%) (P=.003). Advanced Kadish stage, orbital invasion, intracranial invasion, and presence of cervical lymphadenopathy at the time of presentation were significantly associated with poor survival.

ONB has an excellent survival. Surgical resection with PORT when indicated is the mainstay of treatment. Endoscopic approaches can be used as a good tool. Elective neck irradiation reduces the risk of nodal recurrence among patients with clinically N0 neck. Despite the excellent survival, recurrence rate remains high and delayed, highlighting the need for long-term surveillance.

Level 4 Laryngoscope, 2021.

Level 4 Laryngoscope, 2021.

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