Citations

BACKGROUNDProspective quality metrics for neck dissection have not been established for patients with head and neck squamous cell carcinoma. The purpose of this study was to investigate the association between lymph node counts from neck dissection, local‐regional recurrence, and overall survival.METHODSThe number of lymph nodes counted from neck dissection in patients treated in 2 NRG Oncology trials (Radiation Therapy Oncology Group [RTOG] 9501 and RTOG 0234) was evaluated for its prognostic impact on overall survival with a multivariate Cox model adjusted for demographic, tumor, and lymph node data and stratified by the postoperative treatment group.RESULTSFive hundred seventy‐two patients were analyzed at a median follow‐up of 8 years. Ninety‐eight percent of the patients were pathologically N+. The median numbers of lymph nodes recorded on the left and right sides were 24 and 25, respectively. The identification of fewer than 18 nodes was associated with worse overall survival in comparison with 18 or more nodes (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.09‐1.74; P = .007). The difference appeared to be driven by local‐regional failure (HR, 1.46; 95% CI, 1.02‐2.08; P = .04) but not by distant metastases (HR, 1.08; 95% CI, 0.77‐1.53; P = .65). When the analysis was limited to NRG Oncology RTOG 0234 patients, adding the p16 status to the model did not affect the HR for dissected nodes, and the effect of nodes did not differ with the p16 status.CONCLUSIONSThe removal and identification of 18 or more lymph nodes was associated with improved overall survival and lower rates of local‐regional failure, and this should be further evaluated as a measure of quality in neck dissections for mucosal squamous cell carcinoma. Cancer 2016;122:3464–71. © 2016 American Cancer Society.

AbstractShared decision making in emergency medicine has the potential to improve the quality, safety, and outcomes of emergency department (ED) patients. Given that the ED is the gateway to care for patients with a variety of illnesses and injuries and the safety net for patients otherwise unable to access care, shared decision making in the ED is relevant to numerous disciplines and the interests of the United States (U.S.) public. On May 10, 2016 the 16th annual Academic Emergency Medicine (AEM) consensus conference, “Shared Decision Making: Development of a Policy‐Relevant Patient‐Centered Research Agenda” was held in New Orleans, Louisiana. During this one‐day conference clinicians, researchers, policy‐makers, patient and caregiver representatives, funding agency representatives, trainees, and content experts across many areas of medicine interacted to define high priority areas for research in 1 of 6 domains: 1) diagnostic testing; 2) policy, 3) dissemination/implementation and education, 4) development and testing of shared decision making approaches and tools in practice, 5) palliative care and geriatrics, and 6) vulnerable populations and limited health literacy. This manuscript describes the current state of shared decision making in the ED context, provides an overview of the conference planning process, the aims of the conference, the focus of each respective breakout session, the roles of patient and caregiver representatives and an overview of the conference agenda. The results of this conference published in this issue of AEM provide an essential summary of the future research priorities for shared decision making to increase quality of care and patient‐centered outcomes.

Abstract Rationale There is sparse published literature on the causes and outcomes of hospitalization of patients with hereditary hemorrhagic telangiectasia (HHT). Objectives To evaluate rates of various complications, comorbidities, and in-hospital outcomes of patients with HHT using a large, multihospital inpatient database. Methods We identified patients with HHT in the U.S. Nationwide Inpatient Sample between 2000 and 2012. Rates of hemorrhagic, neurological, hepatic, and cardiopulmonary complications among hospitalized patients with HHT were evaluated. We also studied procedure use rates for blood transfusion, endoscopy, and epistaxis treatment. Hospitalization outcomes, including in-hospital mortality, discharge status, charges, and length of stay, were evaluated. Measurements and Main Results: We identified 10,293 patients with HHT. The mean age of the HHT population was 60.7 years. Sixty percent of patients were female. More than 75% of HHT hospitalizations occurred in those older than 50 years of age. Patients with HHT had high rates of bleeding-related complications, including anemia (53.3%), epistaxis (16.2%), and gastrointestinal bleeding (10.8%). Overall, bleeding complications accounted for 62.7% of HHT-related complications. Thirty-eight percent of hospitalized patients with HHT received one or more transfusions of a blood product. Cardiopulmonary complications were present in 41.0% of the cases. Congestive heart failure was the second most common individual complication among patients with HHT, affecting 19.9% of patients. The in-hospital mortality rate was 1.9%. Conclusions In this large, nationwide study, we found that nearly two-thirds of patients hospitalized with HHT experienced a bleeding-related complication. Nearly 40% of hospitalized patients with HHT required transfusion of blood products. Cardiopulmonary complications, including congestive heart failure, were the second most common complication. The high burden of bleeding-related complications points to a significant unmet clinical need for these patients.

Abstract Channelized Hotelling model observer (CHO) methods were developed to assess performance of an x-ray angiography system. The analytical methods included correction for known bias error due to finite sampling. Detectability indices ( d ′ ) corresponding to disk-shaped objects with diameters in the range 0.5–4 mm were calculated. Application of the CHO for variable detector target dose (DTD) in the range 6–240 nGy frame −1 resulted in d ′ estimates which were as much as 2.9× greater than expected of a quantum limited system. Over-estimation of d ′ < ∼ 3.0 was presumed to be a result of bias error due to temporally variable non-stationary noise. Statistical theory which allows for independent contributions of ‘signal’ from a test object (o) and temporally variable non-stationary noise (ns) was developed. The theory demonstrates that the biased d β ′ is the sum of the detectability indices associated with the test object ( d o ′ ) and non-stationary noise ( d ns ′ ). Given the nature of the imaging system and the experimental methods, d o ′ cannot be directly determined independent of d ns ′ . However, methods to estimate d ns ′ independent of d o ′ were developed. In accordance with the theory, d ns ′ was subtracted from experimental estimates of d β ′ , providing an unbiased estimate of d o ′ . Estimates of d o ′ exhibited trends consistent with expectations of an angiography system that is quantum limited for high DTD and compromised by detector electronic readout noise for low DTD conditions. Results suggest that these methods provide d o ′ estimates which are accurate and precise for d o ′ ⩾ ∼ 1.0 . Further, results demonstrated that the source of bias was detector electronic readout noise. In summary, this work presents theory and methods to test for the presence of bias in Hotelling model observers due to temporally variable non-stationary noise and correct this bias when the temporally variable non-stationary noise is independent and additive with respect to the test object signal.

Objectives/HypothesisTo report the preliminary outcomes of patients with single‐sided deafness and asymmetric hearing loss undergoing cochlear implantation at two centers.Study DesignRetrospective review and prospective data collection.MethodsPatients with single‐sided deafness who underwent cochlear implantation at two centers were included. Pre‐ and postoperative measures included monosyllabic word and sentence recognition in quiet for the ear implanted, and sentence recognition in noise in the best‐aided bilateral condition.ResultsAverage monosyllabic word recognition scores in quiet improved significantly from 11.3% (standard deviation [SD] 15.6%) preoperatively to 48.7% (SD 24.2%) at the 3‐month postactivation interval, although they did not increase significantly between the 3‐month and 6‐month intervals. Sentence recognition scores in quiet increased significantly from 18.4% (SD 28.5%) preoperatively to 65.9% (SD 17.9%) at the 3‐month postactivation interval, but not between the 3‐month and 6‐month intervals. Sentence recognition in noise in the best‐aided bilateral condition increased from 59% (SD 16.3%) preoperatively to 72% (SD 16.0%) at 6‐months postactivation, though the difference was not statistically significant. Thirteen of the participants reported tinnitus prior to surgery. Of those, 12 reported that tinnitus was improved after implantation, and one reported that tinnitus was unchanged.ConclusionPreliminary results suggest that speech recognition in a singly deafened ear is significantly improved after cochlear implantation, although speech recognition in noise measured in the bilateral condition remains the same at 6‐months postactivation.Level of Evidence4. Laryngoscope, 127:223–228, 2017

Objectives/HypothesisTo report two patients with a history of microvascular decompression (MVD) for hemifacial spasm who presented with Teflon granulomas (TG) mimicking cerebellopontine angle (CPA) tumors and to perform a systematic review of the English‐language literature.Study DesignCase series at a single tertiary academic referral center and systematic review.MethodsRetrospective chart review with analysis of clinical, radiological, and histopathological findings. Systematic review using PubMed, Embase, MEDLINE, and Web of Science databases.ResultsTwo patients with large skull base TGs mimicking CPA tumors clinically and radiographically were managed at the authors' institution. The first presented 4 years after MVD with asymmetrical sensorineural hearing loss, multiple progressive cranial neuropathies, and brainstem edema due to a growing TG. Reoperation with resection of the granuloma confirmed a foreign‐body reaction consisting of multinucleated giant cells containing intracytoplasmic Teflon particles. The second patient presented 11 years after MVD with asymmetrical sensorineural hearing loss and recurrent hemifacial spasm. No growth was noted over 2 years, and the patient has been managed expectantly. Only one prior case of TG after MVD for hemifacial spasm has been reported in the English literature.ConclusionsTG is a rare complication of MVD for hemifacial spasm. The diagnosis should be suspected in patients presenting with a new‐onset enhancing mass of the CPA after MVD, even when performed decades earlier. A thorough clinical and surgical history is critical toward establishing an accurate diagnosis to guide management and prevent unnecessary morbidity. Surgical intervention is not required unless progressive neurologic complications ensue.Level of Evidence4 Laryngoscope, 127:715–719, 2017

ABSTRACTRare variants (RVs) have been shown to be significant contributors to complex disease risk. By definition, these variants have very low minor allele frequencies and traditional single‐marker methods for statistical analysis are underpowered for typical sequencing study sample sizes. Multimarker burden‐type approaches attempt to identify aggregation of RVs across case‐control status by analyzing relatively small partitions of the genome, such as genes. However, it is generally the case that the aggregative measure would be a mixture of causal and neutral variants, and these omnibus tests do not directly provide any indication of which RVs may be driving a given association. Recently, Bayesian variable selection approaches have been proposed to identify RV associations from a large set of RVs under consideration. Although these approaches have been shown to be powerful at detecting associations at the RV level, there are often computational limitations on the total quantity of RVs under consideration and compromises are necessary for large‐scale application. Here, we propose a computationally efficient alternative formulation of this method using a probit regression approach specifically capable of simultaneously analyzing hundreds to thousands of RVs. We evaluate our approach to detect causal variation on simulated data and examine sensitivity and specificity in instances of high RV dimensionality as well as apply it to pathway‐level RV analysis results from a prostate cancer (PC) risk case‐control sequencing study. Finally, we discuss potential extensions and future directions of this work.

Objectives/HypothesisIdiopathic subglottic stenosis (iSGS) is an unexplained obstruction involving the lower laryngeal and upper tracheal airway. Persistent mucosal inflammation is a hallmark of the disease. Epithelial microbiota dysbiosis is found in other chronic inflammatory mucosal diseases; however, the relationship between tracheal microbiota composition and iSGS is unknown.Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens.MethodsUtilizing 30 human iSGS, 20 intubation‐related tracheal stenosis (iLTS), and 20 healthy control specimens, we applied molecular, immunohistochemical, electron microscopic, immunologic, and Sanger‐sequencing techniques.ResultsWith unbiased culture‐independent nucleic acid, protein, and immunologic approaches, we demonstrate that Mycobacterium species are uniquely associated with iSGS. Phylogenetic analysis of the mycobacterial virulence factor rpoB suggests that, rather than Mycobacterium tuberculosis, a variant member of the Mycobacterium tuberculosis complex or a closely related novel mycobacterium is present in iSGS specimens.ConclusionThese studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention.Level of EvidenceNA Laryngoscope, 127:179–185, 2017

Objectives/HypothesisIdiopathic subglottic stenosis (iSGS) is a rare and devastating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without known antecedent injury or associated disease process. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. Despite the initial clinical description of iSGS more than 40 year ago, there have been no substantive investigations into the pathogenesis of this enigmatic and progressive airway obstruction. In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS.MethodsUtilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and immunologic techniques.ResultsWe demonstrate significant activation of the canonical IL‐23/IL‐17A pathway in the tracheal mucosa of iSGS patients, as well as identify γδ T cells as the primary cellular source of IL‐17A.ConclusionOur results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention.Level of EvidenceNA Laryngoscope, 126:E356–E361, 2016