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OBJECTIVE Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS From the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use.

OBJECTIVES: To describe the demographic and clinical characteristics of pediatric multiple sclerosis (MS) in the United States. METHODS: This prospective observational study included children and adolescents with MS. Cases were evaluated across 9 geographically diverse sites as part of the US Network of Pediatric MS Centers. RESULTS: A total of 490 children and adolescents (324 girls, 166 boys) were enrolled; 28% developed symptoms before 12 years of age. The proportion of girls increased with age from 58% (<12 years) to 70% (≥12 years). Race and ethnicity as self-identified were: white, 67%; African American, 21%; and non-Hispanic, 70%. Most (94%) of the cases were born in the United States, and 39% had 1 or both foreign-born parents. Fifty-five percent of cases had a monofocal presentation; 31% had a prodrome (most frequently infectious), most often among those aged <12 years (P < .001). Children aged <12 years presented more commonly with encephalopathy and coordination problems (P < .001). Sensory symptoms were more frequently reported by older children (ie, those aged ≥12 years) (P < .001); 78% of girls had MS onset postmenarche. The initial Expanded Disability Status Scale score for the group was <3.0, and the annualized relapse rate was 0.647 for the first 2 years. Interval from symptom onset to diagnosis and from diagnosis to initiation of disease-modifying therapy was longer among those <12 years of age. CONCLUSIONS: Pediatric MS in the United States is characterized by racial and ethnic diversity, a high proportion of children with foreign-born parents, and differences in clinical features and timing of treatment among those <12 years of age compared with older children.

Background/aims: Some of the most promising avenues of cancer clinical investigation center on immunotherapeutic approaches. These approaches have provided notable gains in cancer therapeutics with recent Food and Drug Administration approvals of agents of this class in several types of cancers, although gains for ovarian cancer lag behind. This study examined perceptions of therapeutic trials including immunotherapy and virotherapy among ovarian cancer patients and their family members. Methods: A total of 72 semi-structured qualitative interviews were conducted with 33 patients and 39 family members at two National Cancer Institute–designated comprehensive cancer centers. Eligible patients were diagnosed with epithelial ovarian, primary peritoneal, or fallopian tube carcinoma and had experience with clinical trial conversations; family members were nominated by patients and interviewed separately. Applied thematic analysis was used to understand and interpret the data. Results: More participants were aware of vaccine trials than virus trials, although more than half had heard of at least one of them. Initial reactions to vaccine trials were generally favorable. For many, childhood experience with vaccines lent a familiar frame of reference. Virus trials elicited more negative initial reactions, including the use of adjectives such as “scary” and “dreadful.” Viruses seemed contagious or difficult to control. Increased receptivity to these trials occurred in the context of limited therapeutic options and cancer recurrence. Most participants, including those not immediately drawn to these types of trials, indicated openness to learning more. Conclusion: Although vaccine and viral trials are both immunologically based therapeutic approaches, patients who are offered these trials may perceive their potential benefit and safety quite differently. There is a need to consider terminology, solicit and address “gut reactions,” and provide information that enables patients and their family members to better understand the science behind these trials.

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

Abstract Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785–90. ©2016 AACR.

Introduction Under certain circumstances, e-consultations can substitute for a face-to-face consultation. A basic requirement for a successful e-consultation is that the e-consultant has access to important medical history and exam findings along with laboratory and imaging results. Knowing just what information the specialist needs to complete an e-consultation is a major challenge. This paper examines differences between specialties in their need for past information from laboratory, imaging and clinical notes. Methods This is a retrospective study of patients who had an internal e-consultation performed at an academic medical centre. We reviewed a random sample of e-consultations that occurred in the first half of 2013 for the indication for the e-consultation and whether the e-consultant reviewed data in the medical record that was older than one year to perform the e-consultation. Results Out of 3008 total e-consultations we reviewed 360 (12%) randomly selected e-consultations from 12 specialties. Questions on management (35.8%), image results (27.2%) and laboratory results (25%) were the three most common indications for e-consultation. E-consultants reviewed medical records in existence more than one year prior to the e-consultation 146 (40.6%) of the time with e-consultants in the specialties of endocrinology, haematology and rheumatology, reviewing records older than one year more than half the time. Labs (20.3%), office notes (20%) and imaging (17.8%) were the types of medical data older than one year that were reviewed the most frequently overall. Discussion Management questions appear to be the most common reason for e-consultation. E-consultants frequently reviewed historical medical data that is older than one year at the time of the e-consultation, especially in endocrinology, haematology and rheumatology specialties. Practices engaging in e-consultations that require transfer of data may want to include longer time frames of historical information for those specialties.

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