Stephanie Misono

Neurogenin Promotes Neurogenesis and Inhibits Glial Differentiation by Independent Mechanisms

The mechanisms by which neural stem cells give rise to neurons, astrocytes, or oligodendrocytes are beginning to be elucidated. However, it is not known how the specification of one cell lineage results in the suppression of alternative fates. We find that in addition to inducing neurogenesis, the bHLH transcription factor neurogenin (Ngn1) inhibits the differentiation of neural stem cells into astrocytes. While Ngn1 promotes neurogenesis by functioning as a transcriptional activator, Ngn1 inhibits astrocyte differentiation by sequestering the CBP-Smad1 transcription complex away from astrocyte differentiation genes, and by inhibiting the activation of STAT transcription factors that are necessary for gliogenesis. Thus, two distinct mechanisms are involved in the activation and suppression of gene expression during cell-fate specification by neurogenin.

Incidence of Suicide in Persons With Cancer

PURPOSE The purpose of this study was to characterize suicide rates among patients with cancer in the United States and identify patient and disease characteristics associated with higher suicide rates. Prior studies, mostly in Europe, have suggested that patients with cancer may be at increased risk for suicide, but large cohort studies comparing patients with cancer with the general population have not been performed in the United States. METHODS Patients in the study were residents of geographic areas served by the Surveillance, Epidemiology, and End Results (SEER) program who were diagnosed with cancer from 1973 to 2002. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. This was a retrospective cohort study of suicide in persons with cancer. RESULTS Among 3,594,750 SEER registry patients observed for 18,604,308 person-years, 5,838 suicides were identified, for an age-, sex-, and race-adjusted rate of 31.4/100,000 person-years. In contrast, the suicide rate in the general US population was 16.7/100,000 person-years. Higher suicide rates were associated with male sex, white race, and older age at diagnosis. The highest suicide risks were observed in patients with cancers of the lung and bronchus (standardized mortality ratio [SMR] = 5.74; 95% CI, 5.30 to 6.22), stomach (SMR = 4.68; 95% CI, 3.81 to 5.70), oral cavity and pharynx (SMR = 3.66; 95% CI, 3.16 to 4.22), and larynx (SMR = 2.83; 95% CI, 2.31 to 3.44). SMRs were highest in the first 5 years after diagnosis with cancer. CONCLUSION Patients with cancer in the United States have nearly twice the incidence of suicide of the general population, and suicide rates vary among patients with cancers of different anatomic sites. Further examination of the psychological experience of patients with cancer, particularly that of patients with certain types of cancer, is warranted.

Evidence-Based Practice: Evaluation and Management of Unilateral Vocal Fold Paralysis

This article discusses the causes and symptoms, evaluation, and management of unilateral vocal fold paralysis (UVFP). Cross-sectional imaging is appropriate in the work-up of idiopathic UVFP, but the routine use of serology is not well supported. The usefulness of laryngeal electromyography has remained controversial. Predictors of poor prognosis for functionally meaningful recovery include fibrillation potentials, positive sharp waves, and absent/reduced voluntary motor unit potentials. Voice therapy may be helpful. Injection and laryngeal framework surgery (medialization thyroplasty) improve vocal quality. The vocal impact of laryngeal reinnervation is comparable with that of medialization. Some patients may benefit from multiple procedures.

Congenital Cytomegalovirus Infection in Pediatric Hearing Loss

OBJECTIVES To compare the prevalence of congenital cytomegalovirus (CMV) infection in Washington State in children with hearing loss (HL) and the general population and to compare the characteristics of HL in children with and without congenital CMV infection. DESIGN Matched case-control; case cohort. SETTING Regional pediatric hospital, Washington State Department of Health (WSDOH). PATIENTS Cases were children 4 years and older with HL born in Washington State. Control individuals matched for demographic characteristics were identified at random through the WSDOH. MAIN OUTCOME MEASURES Congenital CMV status determined using quantitative polymerase chain reaction testing on newborn heel stick blood spots archived by the WSDOH. Audiologic data were used to characterize HL. RESULTS Congenital CMV testing was performed for 222 matched cases and controls. Congenital CMV infection was detected in 1.4% of controls and in 9.9% of cases (odds ratio, 10.5; 95% confidence interval, 2.6-92.4). An estimated 8.9% of HL in children in Washington can be attributed to CMV infection. After inclusion of an additional 132 children with HL (for a total of 354 cases in the case cohort), we observed that children with congenital CMV had more severe HL (P < .001) and higher proportions of progressive (P = .02) and unilateral (P = .002) HL compared with children without congenital CMV infection. In the 35 children with congenital CMV infection, there was no relationship between neonatal CMV load and severity of HL. CONCLUSIONS In Washington State, children with HL had a far higher prevalence of congenital CMV viremia than did the general pediatric population, and CMV infection seems to be responsible for an appreciable fraction of pediatric HL in Washington State.

Videofluoroscopic findings in dysphagic patients with cricopharyngeal dysfunction: before and after open cricopharyngeal myotomy.

Objectives: Functional outcomes after open cricopharyngeal myotomy (CPM) for Zenkers diverticulum (ZD) and cricopharyngeal dysfunction without diverticulum (CPD) have not been uniformly measured by videofluorographic swallow study (VFSS). Here we characterize preoperative VFSS findings in these groups and evaluate the effect of CPM on swallowing via postoperative VFSS. Methods: We performed a retrospective review of paired preoperative and postoperative VFSS results from 50 patients (36 with ZD and 14 with CPD) over 6 years. Semiquantitative scales were used to assess 1) degree of stasis in the pharyngeal recesses; 2) degree of narrowing at the pharyngoesophageal sphincter (PES); 3) aspiration; and 4) diverticular size. Findings were compared between the groups and across subjects. Results: Pharyngeal stasis was more severe in subjects with CPD than in subjects with ZD, both before and after CPM (p = .02 and p = .0002, respectively). The CPM improved PES narrowing in both groups (p = .03; p = .06) and reduced diverticular size in the ZD group (p < .001), but it did not significantly reduce the stasis severity or the proportion of patients with aspiration. Conclusions: According to VFSS, CPM opens up the PES and decreases diverticular size. More severe stasis in CPD suggests that diffuse pharyngeal weakness may play a role in this disease, and may partially explain the variable post-CPM outcomes that have been observed in CPD.

Use of Specific Neuromodulators in the Treatment of Chronic, Idiopathic Cough: A Systematic Review.

Objective The goal of this systematic review was to examine the evidence for the use of the neuromodulating agents, amitriptyline, gabapentin, pregabalin, and baclofen, in the management of chronic, idiopathic cough patients. Data Sources Online databases, including PubMed, Embase, Cochrane Review, and Web of Science, and publications cited in bibliographies were used. Review Methods Literature was searched by the 2 authors with a priori criteria for study selection. Results Eight relevant articles were identified, including 2 randomized controlled trials, 2 prospective cohort or case-series designs with consecutive patients, 1 retrospective case series of consecutive patients, 1 retrospective case series whose consecutive status was not known, and 2 case reports of 6 and 2 patients, respectively. Improvements in cough-specific quality of life were noted in the randomized controlled trials. Cough severity was reduced in studies that measured this outcome measure. In the remaining studies, cough symptoms were less after neuromodulator treatment. Conclusion Benefit from neuromodulator treatment with amitriptyline, gabapentin, pregabalin, and baclofen in chronic, idiopathic cough patients was demonstrated. Further investigations using objective and subjective outcome measures are needed as well as studies exploring optimal dose, length of treatment, and relapse rates posttreatment.

Treatment and survival in 10,429 patients with localized laryngeal cancer: a population-based analysis.

The objectives of this study were to identify factors associated with treatment differences, characterize changes in treatment patterns over time, and compare survival across treatment types in patients who received treatment for localized laryngeal cancer.

Endoscopic cold incision, balloon dilation, mitomycin C application, and steroid injection for adult laryngotracheal stenosis

To describe the presentation, stenosis characteristics, etiological differences, and outcomes of adult laryngotracheal stenosis treated with endoscopic cold incision, balloon dilation, topical mitomycin C application, and steroid injection.

Voice Outcomes Following Radiation Versus Laser Microsurgery for T1 Glottic Carcinoma Systematic Review and Meta-analysis

Objective Systematic review of literature on patient-reported voice handicap following T1 glottic squamous cell carcinoma treatment using transoral laser microsurgery or radiation therapy. Data Sources PubMed, Web of Science, and Scopus (1997-2013). Review Methods These data sources were searched for papers reporting Voice Handicap Index (VHI) after treatment of early glottic carcinoma. Review and reference cross-checking were performed using a priori selection criteria. Study data were abstracted and publication quality categorized independently by 2 authors. Corresponding authors were contacted to maximize data for analysis. Meta-analysis was performed only with studies that included both treatment modalities, to reduce heterogeneity and maximize rigor; random effects modeling was used to pool results. Results Eighteen publications were identified that reported VHI data following surgery and radiotherapy for T1 glottic carcinoma. No studies were randomized. When studies that reported multiple T-stages or systematic treatment selection bias were excluded, 8 retrospective cohort studies describing 362 patients were suitable for meta-analysis. Follow-up time (mean, 47 months; range, 1-298 mo) and extent of surgical excision varied across studies. Six studies showed no VHI difference between treatment arms; 2 favored radiotherapy over surgery (1 of which reported transmuscular cordectomy for all surgical patients); and none favored surgery. Meta-analysis showed no significant difference in posttreatment VHI between radiotherapy and surgery (mean difference, –5.52; 95% confidence interval, –11.40, 0.36; heterogeneity I2 = 61%, P = .01). Conclusion VHI scores were comparable following transoral laser microsurgery and radiation therapy for T1 glottic carcinoma in the current literature, suggesting no clinically significant difference in functional voice outcomes between treatment types.

Carbon dioxide laser versus stapler-assisted endoscopic Zenker's diverticulotomy: a systematic review and meta-analysis.

To evaluate outcomes following endoscopic management of Zenker’s diverticula using a carbon dioxide laser (CO2) or stapler-assisted technique, a systematic review and meta-analysis were conducted. Seven retrospective, uncontrolled case series including 391 procedures met selection criteria. No higher quality studies were identified. Outcomes favoring the stapler technique included a shorter duration of nil per os (NPO) status (2 studies), length of hospitalization (LOH, 2 studies), and fewer postoperative fevers and abnormal chest x-rays (1 study). Outcomes favoring the CO2 technique included greater improvement in postoperative dysphagia and regurgitation scores (2 studies) and a lower revision rate (1 study). Meta-analysis demonstrated increased nondental complications in the CO2 group (odds ratio 3.81; 95% confidence interval, 1.37-10.59; P = .01) but no difference in duration of NPO (P = .06), LOH (P = .07), overall complications (P = .08), dental complications (P = .57), major complications (P = .38), or revision surgery (P = .82). Implications are limited by the quality of studies identified.