Purpose A subpopulation of pancreatic adenocarcinoma (PDAC) cells is thought to be inherently resistant to chemotherapy or to give rise to tumor cells that become resistant during treatment. Here we determined the role of CD44 expression and its isoforms as a marker and potential target for tumor cells that give rise to invasive and gemcitabine resistant tumors. Experimental Design RT-PCR, Western blotting and DNA sequencing was used to determine CD44 isoform and expression levels. Flow cytometry was used to sort cells on the basis of their CD44 expression level. CD44 expression was knocked down using shRNA. Tumorigenic properties were determined by clonogenic and Matrigel assays, immunohistochemistry, tumor growth in vivo using luciferase imaging and by tumor weight. Results We identified an invasive cell population that gives rise to gemcitabine resistant tumors. These cancer cells express a high level of CD44 standard isoform and have an EMT phenotype (CD44s/EMT). In vivo, CD44s/EMT engraft and expand rapidly and give rise to tumors that express high levels of CD44 isoforms that contain multiple exon variants. CD44 low expressing cells show continued sensitivity to gemcitabine in vivo and knockdown of CD44 in CD44s/EMT cells increases sensitivity to gemcitabine and decreases invasiveness. Conclusion PDAC cells expressing high levels of CD44s with a mesenchymal-like phenotype were highly invasive and developed gemcitabine resistance in vivo. Thus, initial targeting CD44 or reversing the CD44 high phenotype may improve therapeutic response.

Objectives The hypoglossal nerve stimulator (HGNS) is currently approved for the treatment of obstructive sleep apnea (OSA) in patients with an apnea‐hypopnea index (AHI) of >15 to ≤65 events/hour, and a central apnea index (CAI) <25% of the AHI, no complete concentric collapse on drug‐induced sleep endoscopy, and a recommended body mass index (BMI) <32 kg/m2. We present 18 patients implanted as a salvage procedure despite being outside these guidelines. Methods We included all patients who underwent HGNS but who did not meet all FDA guidelines. Demographic data, previous OSA treatments, polysomnographic (PSG) parameters from baseline and HGNS titration PSG, Epworth sleepiness score (ESS), and BMI were compared before and after surgery. Results Eighteen patients were identified: 94.4% male, median age 63 years. Seven underwent previous sleep surgery. Four had an AHI <15 (mean 10.5 events/hour), four had an AHI >65 (mean 86.9 events/hour), two had an elevated CAI (mean 31.3% of AHI), and 12 had a BMI >32 kg/m2 (range 32.1–39.1). Median AHI decreased from 25.3 to 3.75 events/hour on titration polysomnography (P = .0006), oxyhemoglobin saturation nadir increased from 82% to 88.5% (P = .0001) and median ESS dropped from 11 to 7.5 (P = .0016). Fifteen (83.3%) patients achieved surgical success (decrease in AHI >50% and AHI <20 events/hour) and 12 (66.7%) had an AHI <5 events/hour. Neither patient with CAI >25% was successfully treated. Median adherence = 33.5 hours/week. Conclusion Our success rate for patients outside the Food and Drug Administration guidelines for HGNS (67%) was similar to the 1‐year STAR trial results (66%). Future studies are necessary to consider expansion of these guidelines. Level of Evidence 4 Laryngoscope, 130:866–872, 2020

Purpose of review Tongue-base obstruction (TBO) is a common cause of persistent obstructive sleep apnea (OSA) after tonsillectomy and adenoidectomy in children. This review discusses available diagnostic modalities and surgical treatment options for the management of TBO. Recent findings Recently, a systematic review that included nine studies using drug-induced sleep endoscopy (DISE) in the evaluation of children with persistent OSA after tonsillectomy and adenoidectomy identified the tongue-base as the most common site of obstruction. Summary TBO is a common and correctable cause of persistent OSA in children. Diagnostic modalities include awake flexible laryngoscopy, plain neck films, DISE, and cine MRI. Because DISE and cine MRI are performed in a sleep-like state, they are fairly reliable in identifying the site of obstruction. As continuous positive airway pressure is often poorly tolerated in the pediatric population, there is considerable interest in surgical options for TBO. Depending on the location and the severity of the obstruction, interventions such as lingual tonsillectomy, posterior midline glossectomy, tongue suspension suture, epiglottopexy, hypoglossal nerve stimulation, tongue–lip adhesion, and hyoid suspension may play a role in management.

Background: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). Methods: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidencebased review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. Results: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. Conclusion:This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.

Objectives Cornelia de Lange syndrome (CdLS) is a rare genetic disorder. Our goal was to systematically review the literature regarding otolaryngology manifestations of CdLS. Methods We systematically reviewed the PubMed, Embase, CINAHL, Scopus, and Google Scholar databases for original articles of otolaryngology manifestations for patients with CdLS. These articles were analyzed, and pooled prevalence was calculated. Results We analyzed 1,310 patients included in 35 case series and 34 case reports. Hearing loss was present for many patients (27 studies), with sensorineural hearing loss affecting 40.3% (95% confidence interval [CI]: 17.3–63.4) and conductive affecting 22.7% (95% CI: 5.7–39.7). Recurrent acute otitis media was the most frequent infectious manifestation, with 56.5% (95% CI: 34.1–78.4) in seven studies, followed by recurrent airway infections with 44.1% (95% CI: 11.0–87.1) in five studies. Forty‐nine (49.7%) percent of patients (95% CI: 25.9–73.6) in nine studies had dysphagia, and 76.6% (95% CI: 59.8–93.3) in four studies had some degree of dysphonia. Craniofacial anomalies were reported in 30 studies, with micrognathia (53.1%; 95% CI: 34.1–72.1) and high arched palate (70.6%; 95% CI: 56.5–84.8) commonly reported. Additional physical exam abnormalities reported included those involving: lips (76.8%; 95% CI: 65.3–88.4), dentition (65.1%; 95% CI: 27.2–100), mouth (85.5%; 95% CI: 76.2–93.8), and eyelashes (87.1%; 95% CI: 77.2–96.9). Sleep‐disordered breathing or obstructive sleep apnea affected 25.8% (95% CI: 11.4–40.2) of patients (7 studies). Airway anomalies were reported in 11 case reports. Conclusion This is the first comprehensive evaluation of otolaryngologic manifestations in the CdLS literature. Most reported hearing loss and craniofacial anomalies. Sleep disorders occurred in a minority of patients, whereas airway disorders were primarily reported in case reports. These conditions should be further examined given their potential life‐threatening implications. Level of Evidence 3a Laryngoscope, 130:E122–E133, 2020

ObjectivesThe hypoglossal nerve stimulator (HNS) is an effective treatment for obstructive sleep apnea (OSA) in a relatively healthy subset of the population. Our aim was to determine the efficacy of HNS in a veteran population with a high incidence of chronic disease and mental health disorders. Our secondary aim was to compare subjective outcomes and adherence between veterans with and without mental health disorders.MethodsWe included all patients who underwent HNS at our institution to date. Veterans were divided into two groups based on whether or not they carried a diagnosis of anxiety, depression, and/or post‐traumatic stress disorder. Demographics, comorbidities, previous OSA treatments, adverse events, and adherence to therapy were recorded. Baseline and treatment outcome data were collected and analyzed including polysomnographic parameters, Epworth sleepiness scale score (ESS), and body mass index.ResultsThirty‐one patients were identified: 93.5% male, median age = 63.0 years. Median apnea hypopnea index (AHI) decreased from 30.0 to 3.0 events/hour (P < .001) and median ESS dropped from 11.0 to 6.5 (P < .001). There was no difference between groups with regard to change in AHI or ESS (P = .31 and .61). Twenty‐six (89.7%) patients achieved surgical success (decrease in AHI > 50% and AHI < 20 events/hour) and 21 (72.4%) had AHI < 5 events/hour. The mean device usage was 5.4 hours/night which was not significantly different between groups (P = .55).ConclusionOur cohort exhibited similar declines in AHI and ESS compared to published studies with adequate adherence to HNS. There were no significant differences in ESS or adherence to therapy between veterans with and without mental health disorders.Level of Evidence4 Laryngoscope, 130:2275–2280, 2020

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2b. Laryngoscope, 2018.