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The U.S. Department of Agriculture citrus scion breeding program is urgently working on developing huanglongbing (HLB; pathogen Candidatus Liberibacter asiaticus)-tolerant cultivars with excellent fruit quality and productivity when HLB-affected. The slow process of assessing new citrus hybrids is a major impediment to delivery of these much-needed cultivars. We generate thousands of hybrids each year, germinate the seedlings, grow them for 2 years in the greenhouse, plant them at high density in a field where the disease HLB is abundant, grow them for 5 to 10 years, and make selections based on tree performance and fruit quality of these HLB-affected trees. Based on promising reports of accelerated citrus growth when grown in a metallized reflective mulch (MRM) system, we tested the hypothesis that the MRM system may accelerate growth and selection of new hybrid seedlings compared with conventional soil culture (CSC). In the MRM system, tree rows are covered with a layer of metallized plastic film and drip irrigation is installed beneath the plastic. In 2 years of analysis, tree canopy volume was significantly greater with MRM in 2020 (27% greater than CSC) but not in 2021, and MRM tree height was greater in 2021 (7% greater than CSC). Mortality was significantly greater with MRM in both 2020 and 2021(in 2021: 32% vs. 17% under CSC), and MRM trees had more chlorotic leaves. Because of staff limitations, plant debris and soil were not routinely cleared from MRM, thus diminishing any benefit from the reflective surface. Better maintenance might have resulted in more sustained evidence of MRM growth benefits. With the current resource availability, the MRM system does not appear to accelerate the assessment of hybrid seedling trees.

Objective: High-resolution manometry (HRM) provides measures of esophageal function which are used to classify esophageal motility disorders based on the Chicago Classification system. Upper esophageal sphincter (UES) measures are obtained from HRM, but are not included in the classification system, rendering the relationship between UES measures and esophageal motility disorders unclear. Furthermore, changes in the acceptable amount of esophageal dysfunction between versions of this classification system has created controversy. The objective of this study was to determine the relationship between UES measures and esophageal function., Study Design: Cross-sectional study., Setting: Referral centre., Methods: HRM studies from the Calgary Gut Motility Center were reviewed for UES mean basal pressure, mean residual pressure, relaxation time-to-nadir, relaxation duration, and recovery time. Patients were grouped by number of failed swallows according to different iterations of the Chicago Classification: 0 to 4 (Group 1), 5 to 7 (Group 2), and 8 to 10 (Group 3)., Results: 2114 patients (65.1% female, median age 56 y) were included. There were significant increases in UES mean basal pressure (P < .001), mean residual pressure (P < .001), relaxation duration (P < .001), and recovery time (P < .001) between groups. Positive correlations existed between number of failed swallows and UES mean basal pressure (r = 0.143; P < .001), mean residual pressure (r = 0.201; P < .001), relaxation duration (r = 0.145; P < .001), and recovery time (r = 0.168; P < .001)., Conclusions: Differences in UES measures exist among patients with failed swallows, with a positive correlation between UES dysfunction and increasing dysmotility. Our findings illustrate that UES measures are closely related to esophageal function, and that even minor esophageal dysfunction is related to UES dysfunction., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Comparison of the 2007 EORTC/ISCL and the 2022 EORTC/ISCL/USCLC blood staging guidelines for cutaneous T-cell lymphoma at a single institution reveals the newer guidelines fail to detect a subset of patients with Sézary syndrome with low blood burden., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives/hypothesis: Essential vocal tremor (EVT) is an uncommon but challenging condition to manage. Several medical and interventional treatment options have been reported but efficacy remains unclear. We performed a scoping review of high-quality clinical trials to identify effective evidence-based treatments for EVT., Study Design: Scoping review., Methods: Relevant studies were identified using the databases MedLine, Cochrane Central Register of Controlled Trials, and Embase. Subjective and objective outcomes for each modality were analyzed and the effect sizes were quantified using Hedges' g measure to allow comparison between studies., Results: We identified 421 studies eligible for screening with 11 included in the final analysis. Evidence supporting effective EVT treatments was found for bilateral versus unilateral deep brain stimulation (DBS) (Hedges' g 0.65, 95% CI = 0.10-1.20) and octanoic acid (Hedges' g 1.15, 95% CI = 0.40-1.90). Evidence to support the use of methazolamide was not sufficient (Hedges' g 0.51, 95% CI = -0.64 to 1.66). Botulinum toxin (BT) injections were equivalent when comparing unilateral versus bilateral (Hedges' g -0.18, 95% CI = -1.06 to 0.70); BT did not display any advantage over propranolol (Hedges' g -0.47, 95% CI = -1.73 to 0.78) or injection augmentation (Hedges' g 0.068, 95% CI = -0.98 to 1.12)., Conclusions: Our review finds very little high-quality evidence supporting any treatment for EVT. Octanoic acid reduced fluctuations in EVT but did not affect the perception of the tremor. In refractory cases, bilateral DBS was superior to unilateral DBS in improving subjective voice outcomes. Unilateral and bilateral BT injections were equivalent, and BT injection was not more effective than injection augmentation. Further direct comparison in well-designed prospective studies may help clarify optimal treatment for EVT patients., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Microlaryngoscopy is a basic technical skill in Oto-HNS. It is essential for residency programs to have a competency-based assessment tool to evaluate residents' performance of this procedure. An Objective Structured Assessment of Technical Skills (OSATS) is a procedure-specific assessment, which consists of the following: (a) Operation-Specific Checklist and (b) Global Rating Scale (GRS)., Objective: The objective of this study was to create an OSATS for adult microlaryngoscopy., Methods: This was a prospective study, with an initial qualitative phase for OSATS development (Phase I), and a clinical pilot phase (Phase II). In Phase I, interviews were conducted with three laryngologists to establish a stepwise description of adult microlaryngoscopy and review a previously validated GRS for relevance to microlaryngoscopy. Responses were used to create a framework for the OSATS. The OSATS was then presented to Oto-HNS residents and laryngologists in an alternating fashion, for review of clarity and relevance. A pilot study was then performed to evaluate the resident performance of adult microlaryngoscopy. Multiple regression analysis was carried out to investigate whether training level, case complexity, and previous OSATS exposure could predict participant scores., Results: Phase I of this study led to the creation of a 34-item OSATS. The pilot study (N = 28 procedures) revealed that training level was significantly correlated with increased OSATS scores. There was no statistically significant correlation between case complexity and resident scores. Assessors reported the perceived utility of the OSATS and intent for use in residency training., Conclusion: Application of the proposed OSATS will allow for competency-based assessment of the resident performance of microlaryngoscopy., Level of Evidence: NA Laryngoscope, 133:2719-2724, 2023., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Cricopharyngeus muscle dysfunction (CPMD) is a common cause for progressive dysphagia and can lead to dietary restriction, reduced nutrition, weight loss, and pneumonia. Controversy exists whether CPMD is best managed with primary surgical treatment of the cricopharyngeus muscle and who represents a good surgical candidate., Methods: Retrospective review of patients diagnosed with CPMD who underwent surgical treatment were evaluated through prospectively collected pre- and postoperative Eating Assessment Tool-10 (EAT-10) and Functional Oral Intake Scale (FOIS). Videofluoroscopic swallowing studies (VFSS) were reviewed for presence or absence of a high-pressure barium stream through the upper esophageal sphincter, termed the jet phenomenon (JP)., Results: We identified 42 patients with CPMD who underwent surgical treatment and had serial Eating Assessment Tool (EAT-10) measures obtained pre- and postoperatively. Mean EAT-10 scores improved by 12.1 points (95%CI = 8.6-15.6), p < 0.0001. There was a significantly greater improvement among patients with JP (|∆EAT-10|= 17.0, 95%CI = 12.5-21.4) compared to those without (|∆EAT-10|= 6.2, 95%CI = 1.6-10.8), p = 0.0013. Patients with JP also showed improved FOIS score (p = 0.0023) while those without JP did not., Conclusion: This study provides the initial report on the utility of JP as a VFSS feature that is strongly associated with improved outcomes following surgical treatment of CPMD. Further work determining the physiologic correlates responsible for JP will help clarify its predictive capabilities., Level of Evidence: Level 3., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Diagnostic tools for voice disorders are lacking for primary care physicians. Artificial intelligence (AI) tools may add to the armamentarium for physicians, decreasing the time to diagnosis and limiting the burden of dysphonia., Methods: Voice recordings of patients were collected from 2019 to 2021 using smartphones. The Saarbruecken dataset was included for comparison. Audio files were converted to mel-spectrograms using TensorFlow. Diagnostic categories were created to group pathology, including neurological and muscular disorders, inflammatory, mass lesions, and normal. The samples were further separated into sustained/a/and the rainbow passage., Results: Two hundred three prospective samples and 1131 samples were used from the Saarbruecken database. The AI detected abnormal pathology with an F1-score of 98%. The artificial neural network (ANN) differentiated key pathologies, including unilateral paralysis, laryngitis, adductor spasmodic dysphonia (ADSD), mass lesions, and normal samples with 39%-87% F-1 scores. The Calgary database models had higher F-1 scores in a head-to-head comparison to the Saarbruecken and combined datasets (87% vs. 58% and 50%). The AI outperformed otolaryngologists using a standardized test set of recordings (83% compared to 55% ± 15%)., Conclusion: An AI tool was created to differentiate pathology by individual or categorical diagnosis with high evaluation metrics. Prospective data should be collected in a controlled fashion to reduce intrinsic variability between recordings. Multi-center data collaborations are imperative to increase the prediction capability of AI tools for detecting vocal cord pathology. We provide proof-of-concept for an AI tool to assist primary care physicians in managing dysphonic patients., Level of Evidence: 3 Laryngoscope, 133:1952-1960, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Existing field generators (FGs) for magnetic tracking cause severe image artifacts in X-ray images. While FG with radio-lucent components significantly reduces these imaging artifacts, traces of coils and electronic components may still be visible to trained professionals. In the context of X-ray-guided interventions using magnetic tracking, we introduce a learning-based approach to further reduce traces of field-generator components from X-ray images to improve visualization and image guidance., Methods: An adversarial decomposition network was trained to separate the residual FG components (including fiducial points introduced for pose estimation), from the X-ray images. The main novelty of our approach lies in the proposed data synthesis method, which combines existing 2D patient chest X-ray and FG X-ray images to generate 20,000 synthetic images, along with ground truth (images without the FG) to effectively train the network., Results: For 30 real images of a torso phantom, our enhanced X-ray image after image decomposition obtained an average local PSNR of 35.04 and local SSIM of 0.97, whereas the unenhanced X-ray images averaged a local PSNR of 31.16 and local SSIM of 0.96., Conclusion: In this study, we proposed an X-ray image decomposition method to enhance X-ray image for magnetic navigation by removing FG-induced artifacts, using a generative adversarial network. Experiments on both synthetic and real phantom data demonstrated the efficacy of our method., (© 2023. CARS.)

Objectives: To develop an expert consensus statement on the clinical use of swallowing fluoroscopy in adults that reduces practice variation and identifies opportunities for quality improvement in the care of patients suffering from swallowing impairment., Methodology: A search strategist reviewed data sources (PubMed, Embase, Cochrane, Web of Science, Scopus) to use as evidence for an expert development group to compose statements focusing on areas of controversy regarding swallowing fluoroscopy. Candidate statements underwent two iterations of a modified Delphi protocol to reach consensus., Results: A total of 2184 publications were identified for title and abstract review with 211 publications meeting the criteria for full text review. Of these, 148 articles were included for review. An additional 116 publications were also included after reviewing the references of the full text publications from the initial search. These 264 references guided the authors to develop 41 candidate statements in various categories. Forty statements encompassing patient selection, fluoroscopic study choice, radiation safety, clinical team dynamics, training requirements, videofluoroscopic swallow study and esophagram techniques, and interpretation of swallowing fluoroscopy met criteria for consensus. One statement on esophagram technique reached near-consensus., Conclusions: These 40 statements pertaining to the comprehensive use of swallowing fluoroscopy in adults can guide the development of best practices, improve quality and safety of care, and influence policy in both the outpatient and inpatient settings. The lack of consensus on some aspects of esophagram technique likely reflects gaps in knowledge and clinical practice variation and should be a target for future research. Laryngoscope, 133:255-268, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Identification and evaluation of swallowing dysfunction in patients undergoing upper airway surgery for obstructive sleep apnea (OSA) is limited. This study evaluated subjective swallowing function pre and postoperatively in patients undergoing multi-level reconstructive pharyngeal sleep surgery., Methods: A retrospective analysis of prospectively-administered Eating Assessment Tool (EAT-10) scores was conducted among adult patients undergoing surgery for OSA at a tertiary sleep surgery center. Preoperative and 1, 3, and 6-month postoperative time points were assessed. Patients were subdivided into two groups based on the degree of upper airway reconstruction performed. All patients underwent uvulopalatopharyngoplasty +/-tonsillectomy and tongue-base reduction. Patients undergoing Phase 1 reconstructive surgery additionally underwent tongue-base advancement procedures., Results: A total 100 patients underwent airway reconstructive surgery. Forty-one patients underwent Phase 1 surgery; 59 patients underwent Mini-Phase 1 surgery. Neither group demonstrated preoperative dysphagia. Both groups experienced significant subjective dysphagia at 1-month postoperatively, which was greater among Phase 1 patients (mean EAT-10 14.8; SD 10.4) versus Mini-Phase 1 patients (mean EAT-10 6.7; SD 7.5) (p < 0.001). Swallowing function among both groups normalized by 3 and 6 months postoperatively. Phase 1 patients with pre-operative dysphagia (mean EAT-10 9.6; SD 5) demonstrated initial worsening of their swallowing postoperatively; however, reported improved swallowing versus pre-operative levels by 6 months postoperatively (mean EAT-10 3.6; SD 4.3) (p = 0.03)., Conclusion: Pharyngeal surgery resulted in no significant, persistent adverse change in swallowing function. Among both groups, significant subjective dysphagia was reported at 1 month postoperatively, yet returned to preoperative levels by 6 months postoperatively. OSA patients with pre-existing dysphagia undergoing Phase 1 surgery trended towards improved swallowing function postoperatively., Level of Evidence: 2 Laryngoscope, 133:199-204, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To present clinical outcomes of the prospective implementation of the 2015 American Thyroid Association (ATA) guidelines for the management of thyroid nodules and differentiated thyroid cancer (DTC) using the modified ATA recurrence risk (RR) stratification system. Methods: We prospectively analyzed 612 patients with DTC treated between April 2017 and December 2021 in Calgary, Alberta. Each patient was prospectively assigned a modified ATA RR and American Joint Committee Cancer 8th edition stage. Initial risk stratification and consideration of the 2015 ATA guidelines guided surgical management as well as the indication for and dose of radioiodine (RAI) and other adjuvant therapies. Patients were assessed for their response to treatment (RTT) at 2-years postoperatively. Results: There were 479 patients who had 2-year follow-up data and were included in the study. Of these patients, there were 253 (53%) low-, 129 (27%) intermediate-, and 97 (20%) high-RR patients. Of these, 227 patients (47%) underwent total thyroidectomy (TTX) plus RAI, 178 (37%) underwent TTX only, and 74 (16%) underwent lobectomy. The RTT at 2 years was excellent for 89% (66) of patients with lobectomy, 84% (149) for TTX only, and 53% (121) for TTX plus RAI. Among 253 patients who were deemed low RR, 85% (216) had excellent RTT, 13% (32) indeterminate RTT, 2% (4) biochemical incomplete RTT, and 1 patient had structural incomplete RTT. The intermediate RR group had the following RTT outcomes: 64% (83) excellent, 23% (30) indeterminate, 6% (7) biochemical incomplete, and 7% (9) structural incomplete. The high RR group had the worst RTT outcomes, with 38% (37) excellent, 19% (18) indeterminate, 10% (10) biochemical incomplete, and 33% (32) structural incomplete RTT. Conclusions: The 2015 ATA RR stratification system is useful for predicting disease status at 2-year post-treatment in patients with DTC. The 2015 ATA guidelines and modified ATA RR stratification treatment recommendations may reduce thyroid cancer overtreatment by including lobectomy as a definitive treatment option for low-risk thyroid cancers and selective use of RAI for intermediate and high-risk patients.

Objectives: As one of the world's only fully publicly administered, universal healthcare systems, Canada intends to provide equitable access to services for all patients. Socioeconomic status (SES) can affect treatment wait times with implications on health outcomes; however, this has not been evaluated in the setting of laryngeal disease, which incorporates urgent and elective conditions, in a universal healthcare system. This study aims to identify whether SES-affected treatment wait times for laryngeal therapies in this system., Methods: A retrospective review was conducted on a cohort of patients with laryngeal disease at an academic, tertiary center who underwent laryngeal surgery over a three-year period. Data retrieved through medical records; surgical and voice therapy wait times were normalized to each practitioner's average wait time for respective diagnostic categories. Income was used to assess SES and was derived from Statistics Canada census information based on patient postal codes., Results: Data analysis identified 578 patients (59% male). Mean wait time to surgery for all conditions was 123.5 (95% confidence interval 113.1-133.9) days. Analysis of variance analysis found no difference in wait times between different SES groups ( p  = .28), regardless of laryngeal disease category. Patients with cancer or airway obstruction had shorter wait times compared with benign conditions ( p  < .0001)., Conclusions: SES did not affect treatment wait times for laryngeal therapies in a universal healthcare system. Wait times were shorter for oncologic and obstructive conditions compared with benign conditions, reflecting an ability to accommodate clinical needs without impacting care access at the detriment of different SES statuses., Level of Evidence: 4., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC. on behalf of The Triological Society.)

Cricopharyngeus muscle dysfunction (CPMD) is a common cause for progressive dysphagia and can lead to dietary restriction, reduced nutrition, weight loss, and pneumonia. There is a continuum between small, non-obstructive cricopharyngeus bars representing mild disease and severely obstructive bars or Zenker's diverticulum forming late-stage disease, but the natural history of untreated CPMD and the associated time course for progression is unknown. Retrospective longitudinal cohort study from a tertiary outpatient dysphagia centre. Patients diagnosed with CPMD by fluoroscopy and either awaiting surgical treatment or electing non-operative management were evaluated through prospectively collected Eating Assessment Tool-10 (EAT-10) and Functional Oral Intake Scale (FOIS). Review of available imaging identified degree of CPMD. We identified 174 patients with CPMD diagnosed between July 1, 2016, and June 30, 2020; 52 patients had serial Eating Assessment Tool (EAT-10) measures obtained at time of diagnosis and follow up appointment without operative treatment. Mean EAT-10 scores increased from 17.1 to 20.6 (3.5 ± 8.1 points, p = 0.002) points. This change was related to those with a Zenker's diverticulum rather than an isolated cricopharyngeus bar. Dietary outcomes measured by FOIS were stable. While some patients showed fluoroscopic progression of bar size, no patients developed a Zenker's diverticulum from a pre-existing bar in this population. Our data indicate patients with a cricopharyngeus bar do not decline in subjective dysphagia score or diet tolerance, however those with a Zenker's diverticulum worsen over time. This has implications for treatment timing and counselling patients but also reflects a need to understand the pathophysiology behind CPMD and the subset of patients who show progression., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives/hypothesis: Cricotracheal resection (CTR) is an effective treatment for refractory idiopathic subglottic stenosis (iSGS) but is associated with persistent dysphonia. Outcomes were measured longitudinally to characterize how patients' voices and self-perceived voice handicaps changed after CTR., Study Design: Retrospective case-series., Methods: We conducted a retrospective cohort study of patients with refractory iSGS treated by CTR from 2006 to 2017. Voice Handicap Index (VHI), Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V), and acoustic analysis were prospectively collected preoperatively and postoperatively at 1, 3, 6, 12, and 24-month intervals. A linear mixed model was used to evaluate temporal change., Results: Thirty-three patients (97% female) were included. VHI scores increased significantly from baseline preoperative score (27.2 ± 22.7) to a mean value of 44.3 ± 25.6 (P < .001) 1-month postoperatively but decreased below preoperative scores after 2 years (18.8 ± 11.9, P = .795). Mean fundamental frequency (F0) values in speech decreased significantly from 192.0 ± 24.9 Hz preoperatively to 167.1 ± 19.8 Hz at a 2-year follow-up (P = .002), with a nadir value at 1-month postoperatively (148.4 ± 20.5, P < .001). CAPE-V scores increased significantly from preoperative to 1-month postoperative (3.0 ± 2.3 vs. 21.9 ± 17.3, P < .001) but returned toward baseline values at 24 months after CTR (6.9 ± 4.8, P = .027). CAPE-V measurements postoperatively were correlated with VHI and F0 (Pearson coefficient = 0.54 (VHI), -0.46 (F0), P < .001)., Conclusions: Following CTR, mean F0 values were significantly and consistently lower but did increase over time, correlating with patients' improving VHI and CAPE-V scores. VHI values indicate that patient's perception of their voice is not significantly impacted in long term. These results provide a framework to counsel patients about long term voice expectations., Level of Evidence: 4 Laryngoscope, 132:1054-1060, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Residential and occupational exposures to the industrial solvents perchloroethylene (PERC) and trichloroethylene (TCE) present public health concerns. In humans, maternal PERC and TCE exposures can be associated with adverse birth outcomes. Because PERC and TCE are biotransformed to toxic metabolites and placental dysfunction can contribute to adverse birth outcomes, the present study compared the toxicity of key PERC and TCE metabolites in three in vitro human placenta models. We measured cell viability and caspase 3 + 7 activity in the HTR-8/SVneo and BeWo cell lines, and caspase 3 + 7 activity in first trimester villous explant cultures. Cultures were exposed for 24 h to 5-100 µM S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC), or 5-200 µM trichloroacetate (TCA) and dichloroacetate (DCA). DCVC significantly reduced cell viability and increased caspase 3 + 7 activity in HTR-8/SVneo cells at a lower concentration (20 µM) compared with concentrations toxic to BeWo cells and villous explants. Similarly, TCVC reduced cell viability and increased caspase 3 + 7 activity in HTR-8/SVneo cells but not in BeWo cells. TCA and DCA had only negligible effects on HTR-8/SVneo or BeWo cells. This study advances understanding of potential risks of PERC and TCE exposure during pregnancy by identifying metabolites toxic in placental cells and tissues., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Sustainment is a desirable outcome of implementation, but its precise definition remains unclear, contributing to the difficulty of identifying a generalized rate of sustainment. Several studies and reviews on the topic differ on both definition and levels of analysis. Furthermore, methodological limitations might have influenced the results, including the unknown quality with which some interventions were delivered. The Universal Stages of Implementation Completion (UniSIC) is a standardized measurement tool that tracks the implementation process and milestone completion across a wide range of real-world implementations-this provides a unique opportunity to identify a generalized rate of sustainment., Methods: UniSIC data was captured from the SIC website on 27 September 2020 and included data from all sites (n = 1778) that had been tracked to date. Data were restricted to sites that achieved competency in program delivery, and thus had a newly adopted program worthy of sustainment. Dates and indicator variables of implementation activities were combined to form two alternate definitions of sustainment: sustained (start-up) was achieved if sites continued to deliver services 2 years past their program start-up date; sustained (competent) was achieved if sites continued to deliver services 2 years past their competence and/or certification date. Of sites eligible for inclusion based on these definitions (N = 208), descriptive analyses were conducted to determine a rate of sustainment for all programs that successfully started a program. These definitions were also applied to a combined sample for a general rate of sustainment among all sites. Rates of competency among both a sample of sites that started up and a combined sample were also identified., Results: The rate of competence was 58.5% and the rate of sustained (start-up) was 37.1%, while the rate of sustained (competent) was 25.1%. The rates of competence and sustainment among the combined samples were far lower: 15.6% for competence, 6.8% for sustained (start-up), and 4.4% for sustained (competent)., Conclusions: These identified rates of sustainment are accurate initial estimates of sustainment of community-based practices, or in general. Future research on rates of sustainment should carefully define measures of sustainment and be transparent about the real-world conditions on which analyses are centered., (© 2021. The Author(s).)

Zenker's diverticulum (ZD) is an uncommon condition characterized by formation of a pseudodiverticulum in the hypopharynx that presents with considerable variability in swallowing symptomatology. Identifying radiographic features of ZD most associated with clinical impact could prove useful in counseling patients and predicting treatment response. This study was a retrospective case series of patients undergoing videofluoroscopic swallowing studies (VFSS) for Zenker's diverticulum at a tertiary dysphagia center. Anatomic parameters identified on VFSS of patients with ZD were correlated with subjective perception of swallowing using Eating Assessment Tool (EAT-10) scores. Upper esophageal sphincter (UES) opening at the point of maximal distention, area of diverticulum on the lateral view, height of the diverticulum, and entrance angle of the esophagus were measured. We identified 40 patients with ZD (52.5% male, mean age = 71.2 years). Narrow UES opening was significantly correlated with dysphagia severity (r = - 0.3445, p = 0.035). Largest area of diverticulum (r = 0.0188, p = 0.87), diverticulum height (r = 0.1435, p = 0.45), and esophageal entrance angle (r = 0.1677, p = 0.42) were not correlated with EAT-10 scores. Maximum UES opening size was predictive of severity of swallowing dysfunction in patients with ZD. Size of ZD and the angle of bolus entry in patients with ZD are not predictive of swallowing dysfunction. Understanding the predictors of swallowing dysfunction will assist in counseling patients on postoperative expectations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Subglottic stenosis (SGS) is a reportedly rare disease that causes recurrent severe airway obstruction. Etiologies reported for SGS include idiopathic, iatrogenic, autoimmune, congenital, and traumatic, with variable ratios among different centres. From empiric observation, southern and central Alberta was hypothesized to have a disproportionate distribution of SGS driven by increased idiopathic SGS (iSGS) compared to previous literature. Identification of causative agents of iSGS will help understand and guide future management options, so this study aimed to characterize the demographics of SGS subtypes, define prevalence and incidence rates of iSGS in southern Alberta, and geographically analyze for clustering of iSGS prevalence., Methods: SGS patients from Alberta census divisions No. 1-9 and 15 were retrospectively reviewed. Patients were subtyped according to etiology of SGS and characterized. Idiopathic SGS prevalence and incidence was assessed; prevalence was further geographically segregated by census division and forward sortation area (FSA). Significant clustering patterns were assessed for using a Global Moran's I analysis., Results: From 2010 to 2019 we identified 250 SGS patients, who were substantially overrepresented by idiopathic patients (80.4%) compared to autoimmune (10.0%), iatrogenic (7.6%), congenital (1.2%), and traumatic (0.8%). The total iSGS prevalence was 9.28/100,000 with a mean annual incidence rate of 0.71/100,000 per year. Significant clustering was observed (Moran's index 0.125; z-score 2.832; p = 0.0046) and the highest rates of prevalence were observed in southern Alberta and in rural communities heterogeneously dispersed around Calgary FSAs., Conclusion: In southern and central Alberta, iSGS patients were disproportionately over-represented in contrast to other subtypes with the highest prevalence in southern Alberta. There was a three-fold higher annual incidence compared to previous literature demonstrating the highest rates of disease reported worldwide. Future research aims to expand the geographical scope and to assess for demographic or environmental differences within significant clusters that may contribute to disease pathophysiology., Level of Evidence: III., (© 2021. The Author(s).)

Objective: Dysphagia is a common symptom with associated complications ranging from mild discomfort to life-threatening pulmonary compromise. Videofluoroscopic swallow is the 'gold standard' evaluation for oropharyngeal dysphagia, but little is known about how patients' performance changes over time., Method: This was a retrospective cohort study evaluating dysphagia patients' clinical course by serial videofluoroscopic swallow study. Univariate analysis followed by multivariate analysis were used to identify correlations between pneumonia outcomes, diet allocation, aetiology and comorbidities., Results: This study identified 104 patients (53 per cent male) stratified into risk groups by penetration-aspiration scale scores. Mean penetration-aspiration scale worsened over time (p < 0.05), but development of pneumonia was not associated with worsened penetration-aspiration scale score over time (p = 0.57) or severity of dysphagia (p = 0.88)., Conclusion: Our dataset identified a large cohort of patients with oropharyngeal dysphagia and demonstrated mean penetration-aspiration scale tendency to worsen. Identifying prognostic factors associated with worsening radiological findings and applying this to patients at risk of clinical swallowing difficulty is needed.

Trichloroethylene (TCE) is an industrial solvent and widespread environmental contaminant. Although TCE exposure is prevalent, epidemiological studies of TCE exposure associations with adverse birth outcomes are inconclusive. Prior studies show that the TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) exhibits toxicity in a placental cell line. In the current study, genome-wide gene expression and gene set enrichment analyses were used to identify novel genes and pathway alterations in the HTR-8/SVneo human trophoblast cell line and human placental villous explants treated with DCVC at concentrations relevant to human exposures. In the cells, concentration- and time-dependent effects were observed, as evidenced by the magnitude of altered gene expression after treatment with 20 µM DCVC versus 10 µM, and 12-h versus 6-h of treatment. Comparing the two models for the transcriptional response to 12-h 20 µM DCVC treatment, no differentially expressed genes reached significance in villous explants, whereas 301 differentially expressed genes were detected in HTR-8/SVneo cells compared with non-treated controls (FDR < 0.05 + LogFC > 0.35 [FC > 1.3]). GSEA revealed five upregulated enriched pathways in common between explants and cells (FDR < 0.05). Moreover, all 12-h DCVC treatment groups from both models contained upregulated pathways enriched for genes regulated by the ATF4 transcription factor. The overrepresentation of ATF4 regulation of differentially expressed genes indicated activation of the integrated stress response (ISR), a condition triggered by multiple stress stimuli, including the unfolded protein response. DCVC-induced ISR activation was confirmed by elevated eIF2α phosphorylation, ATF4 protein concentrations, and decreased global protein synthesis in HTR-8/SVneo cells. This study identifies a mechanism of DCVC-induced cytotoxicity by revealing the involvement of a specific stress signaling pathway.

Airway reflux is implicated in the pathophysiology of a wide range of adult and pediatric upper and lower airway diseases. However, the diagnosis of proximal reflux-associated disease remains challenging due to evolving clinical criteria and institutional and regional variances in diagnostic practices. Evidence suggests that nonacidic contents of reflux may serve as both pathologic mediators of and biomarkers for reflux in the upper airway. Furthermore, they offer potential pharmaceutical and surgical intervention targets and are the focus of novel clinical diagnostic tools currently under investigation., (© 2020 New York Academy of Sciences.)

Dysphagia is a complex condition with numerous causes, symptoms, and treatments. As such, patients with dysphagia commonly require a multidisciplinary approach to their evaluation and treatment. Integrated multidisciplinary clinics provide an optimal format for a collaborative approach to patient care. In this manuscript, we will discuss considerations for teams looking to build a multidisciplinary dysphagia clinic, including what professionals are typically involved, what patients benefit most from this approach, what tests are most appropriate for which symptoms, financial issues, and traversing interpersonal challenges., (© 2020 New York Academy of Sciences.)

Objectives: Dysfunction of the pharyngoesophageal segment (PES) is a common cause of oropharyngeal dysphagia. Surgical dilation of the PES uses cylindrical dilators that expand radially in a circular shape. Animal studies, however, suggest that the PES is kidney-shaped. The purpose of this investigation was to evaluate the 3D shape of the human PES with a novel casting method., Methods: A platinum-cured liquid silicone polymer was infused under pressure into the upper aerodigestive tract of nine fresh human cadavers to construct 3D casts of the maximally distended PES. Cross-sectional and volumetric analysis were performed using computed tomography and serial sectioning of the models. Canonical variate analysis was used to identify the shape features that best distinguishes the PES from the cervical esophagus., Results: The mean age of the cadavers was 77.9 (SD ± 10.6) years, with 67% women. Analysis of the casts confirms that the human PES possesses a kidney-shaped structure at maximal distention, which is discretely different from the adjacent esophagus (P < 0.001). The posterior body of the cricoid cartilage formed the anterior wall of the PES, which provided a rigid structure responsible for preservation of the kidney shape during distention. The diameter of the maximally distended PES at the cricopharyngeus was highly variable (range = 0.86-4.68 cm 2 ; SD = 1.33 cm 2 )., Conclusion: The data suggest that the human PES is not round and that targeted expansion at the level of the cricopharyngeus with an eccentrically shaped dilator may provide improved distention., Level of Evidence: 4 Laryngoscope, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Swallowing complaints are common and may have significant consequences for nutrition and pulmonary health. Etiology varies and different aspects of the deglutitive system may be affected. A thorough assessment from the oral cavity to the stomach will provide physiologic information that enables specific targeted management plans to be devised. Although the swallow trajectory bridges anatomic areas, there has previously been a tendency to compartmentalize assessment and treatment by arbitrary anatomic boundaries. It is now clear that this approach fails to appreciate the complexity of swallow mechanics and that systems (oral, pharyngeal, esophageal, and pulmonary) are intertwined and codependent. Swallowing specialists from different backgrounds and with complementary skill sets form a multidisciplinary team that can provide insight and address multiple areas of management. With the advent of new tools for instrumental evaluation, such as manometry, targeted rehabilitative strategies can be informed by physiology, increased in precision and breadth, and assessed quantitatively. Surgical approaches have evolved toward endoscopic techniques, and food technology is expanding options in dietary management. The multidisciplinary team is core to managing this varied and often neglected patient population. This review is for clinicians treating swallowing disorders and will explore the selected aspects of the assessment and management of pharyngoesophageal swallowing disorders., (© 2020 New York Academy of Sciences.)

Placental extravillous trophoblast remodeling of the uterine spiral arteries is important for promoting blood flow to the placenta and fetal development. Heparin-binding EGF-like growth factor (HB-EGF), an EGF family member, stimulates differentiation and invasive capacity of extravillous trophoblasts in vitro. Trophoblast expression and maternal levels of HB-EGF are reduced at term in women with preeclampsia, but it is uncertain whether HB-EGF is downregulated earlier when it may contribute to placental insufficiency. A nonhuman primate model has been established in which trophoblast remodeling of the uterine spiral arteries is suppressed by shifting the rise in estrogen from the second to the first trimester of baboon pregnancy. In the present study, we used this model to determine if placental HB-EGF is altered by prematurely elevating estrogen early in baboon gestation. Uterine spiral artery remodeling and placental expression of HB-EGF and other EGF family members were assessed on day 60 of gestation in baboons treated with estradiol (E2) daily between days 25 and 59 of gestation (term = 184 days). The percentages of spiral artery remodeling were 90, 84 and 70% lower (P < 0.01), respectively, for vessels of 26-50, 51-100 and >100 µm diameter in E2-treated compared with untreated baboons. HB-EGF protein quantified by immunocytochemical staining/image analysis was decreased three-fold (P < 0.01) in the placenta of E2-treated versus untreated baboons, while amphiregulin (AREG) and EGF expression was unaltered. Therefore, we propose that HB-EGF modulates the estrogen-sensitive remodeling of the uterine spiral arteries by the extravillous trophoblast in early baboon pregnancy.

Objectives/hypothesis: To determine the volumetric changes in pharyngeal structures in patients with head and neck squamous cell carcinoma (HNSCC) treated with curative chemoradiation therapy (CRT). Patients treated with CRT for esophageal carcinoma (EC), where pharyngeal structures were not part of the radiation treatment fields, were controlled for dysphagia-associated weight loss. We hypothesize that tissue volume alteration is a contributing factor of post-CRT dysphagia., Study Design: Case series., Methods: This study measured pre- and 1-year posttreatment volumes of the base of tongue (BOT), parapharyngeal spaces, posterior pharyngeal constrictors (PCs), and retropharyngeal space (RPS) in patients undergoing CRT for HNSCC or EC treated January 1, 2012 to December 31, 2015. All HNSCC patients were treated to doses of 66 to 70 Gy in 30 to 33 fractions using intensity-modulated radiotherapy techniques., Results: Our cohort included 49 HNSCC and 11 EC patients. Within the HNSCC cohort, the PCs volume increased 1.55 cm 3 (95% confidence interval [CI]: 0.77 to 2.34 cm 3 , P = .0002), RPS increased 1.22 cm 3 (95% CI: 0.67 to 1.77 cm 3 , P < .0001), and BOT decreased 2.29 cm 3 (95% CI: -0.20 to 4.79 cm 3 , P = .070). The EC cohort showed no significant volumetric changes for any anatomic space, with combined PCs and RPS volume changes statistically less than the HNSCC cohort (P = .031). There was no difference in mean body mass index reduction between groups (P = .10)., Conclusions: Volumetric changes following CRT may play a role in posttreatment dysphagia. Our findings support loss of physiologic function from posterior pharynx tissue thickening combined with reduced pharyngeal constriction capacity, and BOT atrophy secondary to radiation effects contribute to dysphagia., Level of Evidence: 4 Laryngoscope, 130:597-602, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Botulinum toxin A (BT) is the gold standard treatment for adductor spasmodic dysphonia (AdSD) with established use for greater than thirty years. The spasmodic dysphonia (SD) literature would benefit from additional long-term cohort data, especially in the Canadian population. The goals of this study were to evaluate whether BT dosage required to achieve acceptable voice shifts over time and to elucidate differences in the subgroups of patients receiving unilateral vocal fold (UVF) injections., Methods: Patient records were retrospectively reviewed at the regional tertiary Voice Clinic for AdSD patients from 1996 to 2017 to identify AdSD patients treated with serial BT injections. Descriptive statistics, paired t-tests for time between treatments and ANOVA tests were used to evaluate trends in subgroup age., Results: One-hundred and twenty-six patients (61% female, mean age = 53 ± 15.5 years) met inclusion criteria and received laryngeal EMG-guided BT injections for up to twenty-two years and as many as 79 treatments. The mean total BT dosage for our population was 1.54 ± 0.35 Units per side. The majority of subjects had decreasing doses over time with a small subgroup having slowly increasing doses. Comparing treatment dosages between unilateral and bilateral injection groups, injection dosage per vocal fold was 1.65 ± 0.62 with time between injections was significantly shorter for the unilateral injection group (mean = 105 days, SD ± 19.8 days, p = 0.005) compared to the bilateral injection subgroup (137 ± 35.7 days, p < 0.005). The mean age of the unilateral injection population as younger at 42.4 ± 11.8 years (p = 0.004)., Conclusion: The majority of patients in this study had decreasing BT injection dosages over time, with a smaller proportion having slowly increasing doses, thought to be likely relating to disease severity. The unilateral vocal fold injections were well tolerated despite needing more frequent injections, and found to be more prevalent in the younger age group.

Objective: To qualitatively assess practices of periprocedural pain assessment and control and to evaluate the effectiveness of interventions for pain during in-office procedures reported in the otolaryngology literature through a systematic review., Data Sources: PubMed, CINAHL, and Web of Science searches from inception to 2018., Review Methods: English-language studies reporting qualitative or quantitative data for periprocedural pain assessment in adult patients undergoing in-office otolaryngology procedures were included. Risk of bias was assessed via the Cochrane Risk of Bias or Cochrane Risk of Bias in Non-Randomized Studies of Interventions tools as appropriate. Two reviewers screened all articles. Bias was assessed by 3 reviewers., Results: Eighty-six studies describing 32 types of procedures met inclusion criteria. Study quality and risk of bias ranged from good to serious but did not affect assessed outcomes. Validated methods of pain assessment were used by only 45% of studies. The most commonly used pain assessment was patient tolerance, or ability to simply complete a procedure. Only 5.8% of studies elicited patients' baseline pain levels prior to procedures, and a qualitative assessment of pain was done in merely 3.5%. Eleven unique pain control regimens were described in the literature, with 8% of studies failing to report method of pain control., Conclusion: Many reports of measures and management of pain for in-office procedures exist but few employ validated measures, few are standardized, and current data do not support any specific pain control measures over others. Significant opportunity remains to investigate methods for improving patient pain and tolerance of in-office procedures.

Prenatal testing for fetal genetic traits and risk of obstetrical complications is essential for maternal-fetal healthcare. The migration of extravillous trophoblast (EVT) cells from the placenta into the reproductive tract and accumulation in the cervix offers an exciting avenue for prenatal testing and monitoring placental function. These cells are obtained with a cervical cytobrush, a routine relatively safe clinical procedure during pregnancy, according to published studies and our own observations. Trophoblast retrieval and isolation from the cervix (TRIC) obtains hundreds of fetal cells with >90% purity as early as five weeks of gestation. TRIC can provide DNA for fetal genotyping by targeted next-generation sequencing with single-nucleotide resolution. Previously, we found that known protein biomarkers are dysregulated in EVT cells obtained by TRIC in the first trimester from women who miscarry or later develop intrauterine growth restriction or preeclampsia. We have now optimized methods to stabilize RNA during TRIC for subsequent isolation and analysis of trophoblast gene expression. Here, we report transcriptomics analysis demonstrating that the expression profile of TRIC-isolated trophoblast cells was distinct from that of maternal cervical cells and included genes associated with the EVT phenotype and invasion. Because EVT cells are responsible for remodeling the maternal arteries and their failure is associated with pregnancy disorders, their molecular profiles could reflect maternal risk, as well as mechanisms underlying these disorders. The use of TRIC to analyze EVT genomes, transcriptomes and proteomes during ongoing pregnancies could provide new tools for anticipating and managing both fetal genetic and maternal obstetric disorders., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Expiratory muscle strength training (EMST) is a treatment for swallowing dysfunction due to its activation of the suprahyoid muscles. Current EMST devices have numerous limitations., Objective: The purpose was to evaluate the utility of elevation training mask as an alternative respiratory muscle strength training (RMST) device., Methods: A closed system, simulating expiration was designed. Air was delivered through a pressure gauge with a measurement range of 0-15 psi. The EMST150TM and the Elevation Training Mask 2.0 ® (ETM) maximal resistance levels were measured and compared., Results: EMST150 produced increasing expiratory resistance pressures of 0.3, 0.6, 1.2, 1.9 and 2.1 psi, which correspond to its indicator of 30, 60, 90, 120 and 150 cmH2O. The ETM resistance pressure produced expiratory resistance pressures of 0.1 and 0.2 psi at simulated altitudes of 3000 and 6000 feet, respectively. A stable expiratory resistance pressure of 0.25 psi was measured at simulated altitudes of 9000, 12,000, 15,000 and 18,000 feet., Conclusion: ETM provides adjustable expiratory muscle strength resistance pressures. Further investigation is necessary to evaluate safety, compliance and clinical efficacy in patients with swallowing dysfunction., Significance: ETM can serve as an effective treatment modality for pulmonary dysfunction and swallowing disorders through RMST.

Insufficient perfusion of the trophoblast by maternal blood is associated with an increased generation of reactive oxygen species and complications of the placenta. In this study, we first examined whether rosiglitazone, an agonist of the peroxisome proliferator-activated receptor-γ (PPARγ), protects the human trophoblast from oxidative injury by regulating key antioxidant proteins, catalase (CAT) and the superoxide dismutases (SOD1 and SOD2). In first trimester placental explants, localization of CAT was limited to cytotrophoblasts, whereas SOD1 was expressed in both the cyto- and syncytiotrophoblasts. In first trimester placental explants, hypoxia decreased the expression of both SOD1 and SOD2, and increased apoptosis. Treatment with rosiglitazone dose-dependently upregulated anti-oxidative CAT and SOD2, and rescued hypoxic injury in first trimester villous explants and JEG-3 cells, strongly suggesting the involvement of the PPARγ in regulating their expressions. Rosiglitazone facilitated transcription activity of PPARγ, and enhanced promotor binding, increased transcriptional activity at the CAT promoter, and elevated protein expression/activity. Treatment of hypoxic JEG-3 cells with rosiglitazone resulted in mitochondrial membrane potential increase and a reduction of caspase 9 and caspase 3 activity which is consistent with improved cell survival. To complement PPARγ activation data, we also utilized the antagonist (SR-202) and siRNA to suppress PPARγ expression and demonstrate the specific role of PPARγ in reducing ROS and oxidative stress. Ex vivo examination of term human placenta revealed lower expression of antioxidant proteins in pathologic compared to healthy placental tissues, which could be rescued by rosiglitazone, indicating that rosiglitazone can improve survival of the trophoblast under pathological conditions. These findings provide evidence that the PPARγ pathway directly influences cellular antioxidants production and the pathophysiology of placental oxidative stress., (© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) is expressed in the embryo and uterus at the implantation site, stimulating trophoblast invasive activity essential for placentation. The effect of extraembryonic HBEGF deficiency on placental development was investigated by breeding mice heterozygous for the Hbegf null mutation. On gestation day 13.5, the average placental weights of the wild-type (Hbegf+/+) and heterozygous (Hbegf+/-) mice were approximately 76 and 77 mg, respectively, as opposed to reduced average placental weights of approximately 61 mg in homozygous null (Hbgef-/-) females. In contrast, fetal weights were not significantly affected by genotype. HBEGF immunostaining in placental sections was Hbegf gene dosage-dependent, while expression of other EGF family members was comparable in Hbegf+/+ and Hbegf-/- placentas. Histological analysis revealed no apparent differences in trophoblast giant cells, but the spongiotrophoblast region was reduced compared to labyrinth (P < 0.05) in Hbegf null placentas. While no differences in cell apoptosis were noted, proliferation as assessed by nuclear Ki67 staining was elevated in the labyrinth and decreased in the spongiotrophoblast region of Hbegf-/- placentas. Labyrinth morphology appeared disrupted in Hbegf -/- placentas stained with laminin, a marker for capillary basement membrane, and the capillary density was reduced. Immunohistochemical staining revealed reduced vascular endothelial growth factor (VEGF) levels in both spongiotrophoblast and labyrinth (P < 0.01) regions of Hbegf-/- placentas. In vitro, HBEGF supplementation increases the expression of VEGF in a human trophoblast cell line. These findings suggest that trophoblast HBEGF promotes placental capillary formation by inducing VEGF in the developing placenta of mice.

Objective: Calcium hydroxyapatite (CaHA) is a common material for vocal fold injection augmentation. Durability is variable, and factors involved in implant longevity are not understood. Animal models of osteoporosis show decreased bone density and increased mineral liberation, suggesting CaHA retention may be altered in these conditions., Study Design: Prospective murine investigation., Methods: Fourteen skeletally mature, 10-month-old female Sprague-Dewley rats were treated by one of three interventions: oophorectomy, laparotomy without oophorectomy (sham), or monthly risedronate injection (90 μg/kg, subcutaneous). CaHA was implanted into the right lateral thigh muscle in all animals at the time of procedure or first risedronate injection. After 17 weeks, all rats were sacrificed, and the residual CaHA isolated from excised lateral thigh muscle through incubation in a 900 °C calcinator for 9 hours., Results: Mean CaHA mass remaining in the oophorectomy group was 65.9 (standard deviation ± 16.1) mg, compared to 44.4 ± 10.0 mg CaHA in the risedronate group and 48.6 ± 7.5 mg in the sham group. One-way analysis of variance found a statistically significant difference between the oophorectomy and risedronate groups but not between the sham and other groups, F(2,11) = 4.404, P = 0.039., Conclusion: Persistent estrogen deficiency in a murine model of osteoporosis demonstrated decreased rate of CaHA resorption. This suggests that hormone alterations associated with osteoporosis may alter the longevity of CaHA implant resorption through an uncertain mechanism., Level of Evidence: NA. Laryngoscope, 2576-2580, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Pharyngoesophageal foreign bodies (FBs) are common otolaryngologic problems, but challenging cases cause significant patient and surgeon frustration. Extraluminal migration of an FB from the pharynx or esophagus is rare and usually necessitates external neck exploration. Approaching these complicated FBs endoscopically may avoid undue surgical morbidity. We present a case using real-time, intraoperative ultrasound (US) guidance for safe retrieval of a migrated submucosal FB. Intraoperative US is a widely available, powerful technology that can aid in the retrieval of difficult pharyngoesophageal FBs. In appropriate cases, this strategy may circumvent transcervical approaches and their associated risks.

Background: Early during human development, the trophoblast lineage differentiates to commence placentation. Where the placenta contacts the uterine decidua, extravillous trophoblast (EVT) cells differentiate and invade maternal tissues. EVT cells, identified by expression of HLA-G, invade into uterine blood vessels (endovascular EVT), as well as glands (endoglandular EVT), and open such luminal structures towards the intervillous space of the placenta. Endoglandular invasion diverts the contents of uterine glands to the intervillous space, while glands near the margin of the placenta that also contain endoglandular EVT cells open into the reproductive tract. Cells of the trophoblast lineage have thus been recovered from the uterine cavity and endocervical canal. An emerging non-invasive technology [trophoblast retrieval and isolation from the cervix (TRIC)] isolates and examines EVT cells residing in the cervix to explore their origin, biology and relationship to pregnancy and fetal status., Objective and Rationale: This review explores the origins and possible uses of trophoblast cells obtained during ongoing pregnancies (weeks 5-20) by TRIC. We hypothesize that endoglandular EVT cells at the margins of the expanding placenta enter the uterine cavity and are carried together with uterine secretion products to the cervix where they can be retrieved from a Papanicolaou (Pap) smear. The advantages of TRIC for investigation of human placentation and prenatal testing will be considered. Evidence from the literature, and from archived in utero placental histological sections, is presented to support these hypotheses., Search Methods: We used 52 out of 80 publications that appeared between 1966 and 2017 and were found by searching the PubMed and Google Scholar databases. The studies described trophoblast invasion of uterine vessels and glands, as well as trophoblast cells residing in the reproductive tract. This was supplemented with literature on human placental health and disease., Outcomes: The literature describes a variety of invasive routes taken by EVT cells at the fetal-maternal interface that could displace them into the reproductive tract. Since the 1970s, investigators have attempted to recover trophoblast cells from the uterus or cervix for prenatal diagnostics. Trophoblast cells from Pap smears obtained at 5-20 weeks of gestation have been purified (>95% β-hCG positive) by immunomagnetic isolation with nanoparticles linked to anti-HLA-G (TRIC). The isolated cells contain the fetal genome, and have an EVT-like expression profile. Similar EVT-like cells appear in the lumen of uterine glands and can be observed entering the uterine cavity along the margins of the placenta, suggesting that they are the primary source of cervical trophoblast cells. Cells isolated by TRIC can be used to accurately genotype the embryo/fetus by targeted next-generation sequencing. Biomarker protein expression quantified in cervical trophoblast cells after TRIC correlates with subsequent pregnancy loss, pre-eclampsia and fetal growth restriction. A key remaining question is the degree to which EVT cells in the cervix might differ from those in the basal plate and placental bed., Wider Implications: TRIC could one day provide a method of risk assessment for maternal and fetal disease, and reveal molecular pathways disrupted during the first trimester in EVT cells associated with placental maldevelopment. As perinatal interventions emerge for pregnancy disorders and inherited congenital disorders, TRIC could provide a key diagnostic tool for personalized precision medicine in obstetrics.

The p21-activated kinase 2 (Pak2), an effector molecule of the Rho family GTPases Rac and Cdc42, regulates diverse functions of T cells. Previously, we showed that Pak2 is required for development and maturation of T cells in the thymus, including thymus-derived regulatory T (Treg) cells. However, whether Pak2 is required for the functions of various subsets of peripheral T cells, such as naive CD4 and helper T-cell subsets including Foxp3 + Treg cells, is unknown. To determine the role of Pak2 in CD4 T cells in the periphery, we generated inducible Pak2 knockout (KO) mice, in which Pak2 was deleted in CD4 T cells acutely by administration of tamoxifen. Temporal deletion of Pak2 greatly reduced the number of Foxp3 + Treg cells, while minimally affecting the homeostasis of naive CD4 T cells. Pak2 was required for proliferation and Foxp3 expression of Foxp3 + Treg cells upon T-cell receptor and interleukin-2 stimulation, differentiation of in vitro induced Treg cells, and activation of naive CD4 T cells. Together, Pak2 is essential in maintaining the peripheral Treg cell pool by providing proliferation and maintenance signals to Foxp3 + Treg cells., (© 2018 The Authors. Immunology Published by John Wiley & Sons Ltd.)

Background: Cricopharyngeus muscle dysfunction (CPMD) is a common cause of dysphagia. We employ a progressive series of three double-balloon dilations separated by 4-6 weeks between procedures as a primary treatment option. The purpose of this study was to evaluate subjective, functional and objective improvement in swallowing after three serial dilations for CPMD., Methods: We retrospectively evaluated patients between June 1, 2014, and June 30, 2016, who underwent a series of three double-balloon dilations for CPMD. Pre- and post-dilation Eating Assessment Tool-10 (EAT-10), Functional Oral Intake Scale (FOIS), pharyngeal constriction ratio, pharyngeal area, and pharyngoesophageal segment (PES) opening were compared., Results: Seventeen patients with CPMD underwent serial double-balloon dilation procedures separated by one month. Mean age of the cohort was 73.5 (SD ± 13.3) years, and 53% were female. The mean EAT-10 improved from 24.7 (SD ± 7.8) to 15.9 (SD ± 10.2) [p = 0.0021]. Mean FOIS improved from 5.4 (SD ± 1.4) pre- to 6.3 (SD ± 0.9) post-treatment (p = 0.017). Mean UES opening increased from 1.05 (SD ± 0.34) cm to 1.48 (SD ± 0.41) cm (p = 0.0003) in the anteroposterior fluoroscopic view and from 0.58 (SD ± 0.18) to 0.76 (SD ± 0.30) cm (p = 0.018) in the lateral view. Pharyngeal constriction ratio (PCR), a surrogate measure of pharyngeal strength, improved from 0.49 (SD ± 0.37) to 0.24 (SD ± 0.15) (p = 0.015), however pharyngeal area (PA) was unchanged., Conclusions: A progressive series of three double-balloon dilations for cricopharyngeus muscle dysfunction resulted in improved patient reported dysphagia symptom scores and objective fluoroscopic swallowing parameters.

Background: Traumatic laryngeal injuries are uncommon life-threatening injuries that require prompt, rational management of a potentially precarious airway. It is unclear whether the current incidence of laryngotracheal injury is due to enhanced injury detection or increased occurrence. The objective of this study was to evaluate the relations between diagnostic imaging with both initial airway management and surgical treatment in patients with external laryngotracheal injuries (ELTIs) in Alberta., Methods: In this large-scale population-based analysis, we used regional health databases containing inpatient admissions, emergency department visits and trauma service activations employing International Classification of Diseases diagnostic codes to identify all ELTIs diagnosed from Apr. 1, 1995, to Dec. 31, 2011, in adults (age ≥ 16 yr). We evaluated health records and diagnostic imaging for injury features, airway management, operative interventions and hospital length of stay (LOS)., Results: Eighty-nine patients met the inclusion criteria. The incidence of ELTIs increased over time, paralleling a rise in detection during the period incorporating greater computed tomography (CT) use ( p = 0.002). Endotracheal tube intubation was performed in 8/30 cases (27%) in the pre-CT era, compared to 38/59 cases (64%) in the post-CT era ( p = 0.001); the use of surgical intervention remained consistent. The largest contributors to increased endotracheal tube placements were the emergency department and emergency medical services. No change in survival was detected, but mean LOS among patients admitted for minor, isolated ELTIs increased by 2.3 (95% confidence interval 0.14-4.8) days ( p = 0.06), mostly for patients admitted under critical care for mechanical ventilation., Conclusion: Management of ELTIs shifted from predominantly conservative airway monitoring to endotracheal tube intubation over the study period in spite of no clinically significant change in injury severity or operative intervention frequency. The location of endotracheal tube placement suggests less comfort with ELTI among first-responder and emergency personnel.

Objective The rate of balloon dilator failure is unknown, and a rescue strategy for device malfunction has not been established. The purposes of this investigation were to determine the approximate number of balloon failures in the gastrointestinal tract and airway, evaluate the parameters required to rupture balloon dilators, and develop a rescue strategy to efficiently reestablish airway patency. Study Design Retrospective cohort and basic medical research. Setting Academic tertiary care medical center. Subjects and Methods The Manufacturer and User Facility Device Experience database was queried for adverse events associated with tracheal and esophageal dilators between January 1, 2014, and January 1, 2017. A bench-top model of airway stenosis was developed, and optimal conditions for the safe removal of a malfunctioning dilator were assessed (2, 4, 6 atm). Results There were 420 reported balloon malfunctions, including 104 cases with deflation/removal issues. The bench-top model determined that device rupture allowing for immediate removal occurs with needle puncture at balloon pressures ≥8 atm. Balloons inflated to 6 atm required a median of 17.5 seconds (range, 0-55.3) for removal, in comparison with 30.2 seconds (range, 7.1-87.5) at 2 atm ( P > .05). Conclusion Balloon dilator malfunction is a significant problem that practitioners must be prepared for. Pressure ≥8 atm (~33% overinflation) is required to consistently cause complete balloon dilator rupture via needle puncture. While counterintuitive, increasing the inflation pressure of a malfunctioning balloon (8-10 atm) may expedite rupture and safe removal. A rescue strategy for balloon malfunction is proposed.