Smad3: an emerging target for vocal fold fibrosis.

OBJECTIVES/HYPOTHESIS: To determine the efficacy of small interfering RNA (siRNA) targeting Smad3 to mediate fibroplasia in vitro, to investigate the temporal regulation of Smad3 following vocal fold (VF) injury, and to determine the local and distal effects of Smad3 siRNA VF injection. STUDY DESIGN: In vitro and in vivo. METHODS: In vitro, Smad3 regulation was examined at both the level of transcription and translation in a human VF cell line in response to Smad3 siRNA ± transforming growth factor ß (TGF-ß). Collagen transcription was also examined. In vivo, Smad3 messenger RNA (mRNA) expression was quantified as a function of time following rabbit VF injury. Also, the effects of injected Smad3 siRNA were assessed at local and distal sites. RESULTS: Smad3 siRNA knocked down Smad3 transcription and translation and limited TGF-ß-mediated collagen mRNA expression with minimal cytotoxicity in vitro. In vivo, Smad3 mRNA increased 1 day following VF injury and remained elevated through day 7. Smad3 siRNA injection into the uninjured vocal fold had no local or distant effect on Smad3 mRNA at multiple organ sites. CONCLUSIONS: These data provide a foundation for further investigation regarding the development of novel RNA-based therapeutics for the VF, specifically locally delivered siRNA for challenging fibrotic conditions of the VF.

Hoarseness and laryngopharyngeal reflux: a survey of primary care physician practice patterns.

IMPORTANCE: Current approaches to the diagnosis and subsequent management of specific voice disorders vary widely among primary care physicians (PCPs). In addition, sparse literature describes current primary care practice patterns concerning empirical treatment for vocal disorders. OBJECTIVE: To examine how PCPs manage patients with dysphonia, especially with regard to laryngopharyngeal reflux. DESIGN, SETTING, AND PARTICIPANTS: Prospective, questionnaire-based study by an academic laryngology practice among academic PCPs from all major US geographic regions. MAIN OUTCOMES AND MEASURES: A 16-question web-based survey, distributed via e-mail, concerning management and possible empirical treatment options for patients with dysphonia. RESULTS: Of 2441 physicians who received the e-mail broadcast, 314 (12.9%) completed the survey. Among those who completed the survey, 46.3% were family practitioners, 46.5% were trained in internal medicine, and 7.2% identified as specialists. Among all respondents, 64.0% preferred to treat rather than immediately refer a patient with chronic hoarseness (symptoms persisting for >6 weeks) of unclear origin. Reflux medication (85.8%) and antihistamines (54.2%) were the most commonly selected choices for empirical treatment. Most physician respondents (79.2%) reported that they would treat chronic hoarseness with reflux medication in a patient without evidence of gastroesophageal reflux disease. CONCLUSIONS AND RELEVANCE: Most PCPs who responded to our survey report empirically treating patients with chronic hoarseness of unknown origin. Many physician respondents were willing to empirically prescribe reflux medication as primary therapy, even when symptoms of gastroesophageal reflux disease were not present. These data suggest that PCPs strongly consider reflux a common cause of dysphonia and may empirically treat patients having dysphonia with reflux medication before referral.

Glucocorticoids in laryngology: a review.

OBJECTIVES/HYPOTHESIS: To provide the otolaryngologist an evidence-based sound review of glucocorticoid use for laryngeal pathology. STUDY DESIGN: Review of contemporary peer-reviewed literature as well as review articles. METHODS: A review of the literature regarding glucocorticoids as a therapeutic intervention for the treatment of benign laryngeal pathology and laryngeal manifestations of systemic disease was performed. Review included both systemic administration as well as local injection. RESULTS: Glucocorticoids, administered in the critical care setting for planned extubation, markedly reducing the risk of reintubation and remain a rudimentary pharmacologic adjunct in laryngeal manifestations of common autoimmune and inflammatory disorders. Intralesional injection has reduced the rate of surgical intervention for benign inflammatory primary laryngeal pathology. CONCLUSIONS: Glucocorticoids are effective in the treatment of a number of laryngeal pathologies, through both systemic and intralesional administration. However, a clear consensus for utilization of glucocorticoids in the treatment of specific laryngeal disorders has yet to be published.

Glucocorticoids for vocal fold disease: a survey of otolaryngologists.

OBJECTIVE/HYPOTHESIS: Glucocorticoids (GCs) are commonly used in the treatment of laryngeal disorders despite the absence of clear guidelines regarding their use. We sought to assess clinical practice patterns regarding GC use for various vocal fold diseases and to ascertain factors underlying the selection of particular GCs for different vocal fold pathology. STUDY DESIGN: Prospective, survey. METHODS: A web-based 20-question survey querying clinical indications for GC use and other factors influencing decision making in GC administration was distributed to 5280 otolaryngologists via e-mail using a commercially available database. RESULTS: The overall response rate for the survey was 4% (212/5280). Of the respondents, 99% reported GCs to be valuable in their practice. Previous experience/results, familiarity, and use in practice (68%, 54%, and 37%, respectively) were the most commonly cited reasons for choosing a particular GC; pharmacokinetic profile and academic literature were infrequently cited reasons. Fifty-four percent of respondents were more likely to prescribe GCs for vocal performers compared with other patients. Additionally, most respondents stated that the potential for side effects only occasionally prevented GC utilization. CONCLUSIONS: GC prescription practices vary greatly among otolaryngologists. Drug choice appears to be driven primarily by clinician preference and personal experience rather than by specific pharmacologic or physiologic rationale. These findings likely reflect the current lack of well-constructed studies in the laryngology literature to guide GC selection and administration for benign disorders of the larynx and highlight an important potential area for future studies.

Incidence of underlying laryngeal pathology in patients initially diagnosed with laryngopharyngeal reflux.

OBJECTIVES/HYPOTHESIS: To characterize the videoendoscopic laryngeal findings in patients with a prior established diagnosis of laryngopharyngeal reflux disease (LPR) as the sole etiology for their chief complaint of hoarseness. We hypothesized that many, if not all, of these patients would present with discrete laryngeal pathology, divergent from LPR. STUDY DESIGN: Prospective, nonintervention. METHODS: Patients presenting to a tertiary laryngology practice with an established diagnosis of LPR as the sole etiology of their hoarseness were included. All subjects completed the Voice Handicap Index and Reflux Symptom Index, in addition to a questionnaire regarding their reflux diagnosis and prior treatment. Laryngoscopic examinations were reviewed by the laryngologist caring for the patients. Reliability of findings was assessed by interpretation of videoendoscopic findings by three outside laryngologists not involved in the care of the patients. RESULTS: Laryngeal pathology distinct from LPR was identified in all 21 patients felt to be causative of the chief complaint of dysphonia. Specifically, the most common findings were benign mucosal lesions and vocal fold paresis (29% each), followed by muscle tension dysphonia (14%). Two patients were found to have vocal fold leukoplakia, of which one was confirmed to be a microinvasive carcinoma upon removal. CONCLUSION: LPR may be overdiagnosed; other etiologies must be considered for patients with hoarseness who fail empiric LPR treatment. LEVEL OF EVIDENCE: 4.

Morbidity and patient perception of flexible laryngoscopy.

OBJECTIVES: The recently published Clinical Practice Guideline: Hoarseness (Dysphonia) revealed major deficits in the literature regarding relatively routine clinical decision-making. One of the more controversial points in the Guideline regarded the utility and timing of laryngeal visualization via flexible laryngoscopy, potentially because of sparse literature regarding the risks and potential morbidity. We sought to prospectively address this issue in order to optimize evaluation protocols. METHODS: Two-hundred fifty consecutive patients with a variety of complaints completed a survey after undergoing flexible laryngoscopy. The survey queried 1) demographics; 2) discomfort of pretreatment anesthesia and scope placement in the nose and pharynx; 3) fear of future examinations; and 4) patient perception and past experience. Concurrently, the laryngoscopist reported the complications and anatomic variations encountered. RESULTS: The discomfort and pain ratings from both the anesthetic spray and the scope placement were low. No statistically significant differences were observed with regard to sex; however, women reported greater fear associated with examinations (p = 0.0001). Anatomic abnormalities were observed in 14.4% of patients, and these patients reported greater discomfort, pain, and fear regarding the examination. No adverse events were observed. CONCLUSIONS: Flexible laryngoscopy was well tolerated, with little to no risk. The presence of nasal anatomic abnormalities predicted increased discomfort.

Sideways displacement of the endograft within the aneurysm sac is associated with late adverse events after endovascular aneurysm repair.

OBJECTIVE: Previous studies have shown the importance of proximal and distal endograft fixation. There is little information on the middle, unsupported section of endograft within the aneurysm sac. We quantified sideways movement of the endograft within the aneurysm sac and correlated it to late adverse events. METHODS: Patients who underwent endovascular abdominal aortic aneurysm (AAA) repair with a suprarenal or infrarenal endograft between January 1997 and December 2007 were analyzed for sideways endograft movement. Patients were included if they had a digital preoperative computed tomography angiogram (CTA), a postoperative CTA within 3 months after the index procedure, and at least one follow-up CTA thereafter with a minimal time interval of 6 months. The endograft position within the aneurysm sac was quantitated on cross-sectional images using a fixed vertebral body reference point. Patients with change in endograft position ≥5 mm were placed in the sideways displacement (SD) group and compared with patients with no displacement (ND; <5 mm change in position). The relationship between sideways endograft movement and endovascular aneurysm repair (EVAR)-related complications were noted for AAA rupture, AAA-related death, conversion, secondary procedures, AAA growth (≥5 mm), proximal migration (≥10 mm), and new onset of type I or III endoleaks. RESULTS: The study included 144 patients (mean age, 76 ± 7.6 years). Mean follow-up time was 43 ± 27 months. Fifty patients (35%) had sideways endograft movement ≥5 mm during follow-up. Baseline AAA diameter was larger (SD 60 ± 9 mm vs ND 57 ± 9 mm; P < .05) and proximal and iliac endograft fixation lengths were shorter (SD 18 ± 8 mm vs ND 24 ± 11 mm; P < .05 and SD 35 ± 14 vs ND 42 ± 16 mm; P < .05) in patients with sideways endograft displacement. There was no significant difference between the groups in AAA rupture and AAA-related death (one fatal AAA rupture, ND group). SD patients had a higher surgical conversion rate (10% vs 0%; P = .002), more secondary procedures (44% vs 6%; P < .001), more AAA sac enlargement (42% vs 10%; P < .001), more endograft migration (66% vs 5%; P < .001), and more type I or III endoleaks (36% vs 3%; P < .001). CONCLUSIONS: Positional stability of the endograft within the aneurysm sac is critical for the long-term success of EVAR. Sideways movement of the endograft within the aneurysm sac is associated with an increased risk of late adverse events.

Current concepts in the management of the aging forehead in facial plastic surgery.

PURPOSE OF REVIEW: This article reviews the significant recent literature on the constantly evolving approach to surgical rejuvenation of the forehead and brow. RECENT FINDINGS: Recent literature describes a variety of modifications to traditional endoscopic approaches, particularly regarding new permanent and temporary fixation techniques. There is continued effort to deepen our understanding of upper facial anatomy and its relationship to the aging process. As interest and research in this area continue to grow, improved quantification of surgical results becomes important. SUMMARY: There has been significant development and refinement of endoscopic approaches to foreheadplasty. Nonetheless, debate regarding the durability, quality of results, and complications of endoscopic versus open approaches continues. Ultimately, optimal results may be achieved through a variety of surgical techniques, but require a thorough understanding of the anatomic basis of aging, attention to detail, and adequate brow fixation.

Integration of patient-specific paranasal sinus computed tomographic data into a virtual surgical environment.

BACKGROUND: The advent of both high-resolution computed tomographic (CT) imaging and minimally invasive endoscopic techniques has led to revolutionary advances in sinus surgery. However, the rhinologist is left to make the conceptual jump between static cross-sectional images and the anatomy encountered intraoperatively. A three-dimensional (3D) visuo-haptic representation of the patient's anatomy may allow for enhanced preoperative planning and rehearsal, with the goal of improving outcomes, decreasing complications, and enhancing technical skills. METHODS: We developed a novel method of automatically constructing 3D visuo-haptic models of patients' anatomy from preoperative CT scans for placement in a virtual surgical environment (VSE). State-of-the-art techniques were used to create a high-fidelity representation of salient bone and soft tissue anatomy and to enable manipulation of the virtual patient in a surgically meaningful manner. A modified haptic interface device drives a virtual endoscope that mimics the surgical configuration. RESULTS: The creation and manipulation of sinus anatomy from CT data appeared to provide a relevant means of exploring patient-specific anatomy. Unlike more traditional methods of interacting with multiplanar imaging data, our VSE provides the potential for a more intuitive experience that can replicate the views and access expected at surgery. The inclusion of tactile (haptic) feedback provides an additional dimension of realism. CONCLUSION: The incorporation of patient-specific clinical CT data into a virtual surgical environment holds the potential to offer the surgeon a novel means to prepare for rhinologic procedures and offer training to residents. An automated pathway for segmentation, reconstruction, and an intuitive interface for manipulation may enable rehearsal of planned procedures.

Lateral movement of endografts within the aneurysm sac is an indicator of stent-graft instability.

PURPOSE: To determine if lateral movement of an aortic endograft 1 year following endovascular abdominal aortic aneurysm (AAA) repair is an indicator of endograft instability and can serve as a predictor of late adverse events. METHODS: The records of 60 high-risk AAA patients (52 men, 8 women; mean age 74 years) who were treated with infrarenal (n = 38) or suprarenal (n = 22) endografts and had serial computed tomograms (CT) over > or =12 months were analyzed. Postimplantation and 1-year CT scans were compared, and changes in endograft position within the aneurysm sac [lateral movement (LM) versus no lateral movement (NM)] were measured using a vertebral body reference point. Longitudinal endograft movement was measured with respect to the superior mesenteric artery along the aortic centerline axis. Long-term adverse event rates (endoleaks, secondary procedures, conversion, rupture, and death) were assessed. RESULTS: One year after endograft implantation, LM > or =5 mm was present in 16 (27%) patients; 44 (73%) endografts demonstrated no lateral movement. LM patients had larger aneurysms (6.5+/-1.5 versus 5.6+/-0.9 cm, p = 0.02) and a longer endograft-to-hypogastric artery length (p = 0.01) than NM patients. There were no significant differences between patients treated with infrarenal and suprarenal endografts. At 1 year, longitudinal migration > or =10 mm occurred in 5 (31%) of the LM patients versus 2 (5%) in the NM cohort (p<0.0001). There were no significant differences in adverse event rates between LM and NM at 1 year. However, during long-term follow-up (mean 54+/-26 months, range 12-102), 8 (50%) LM patients developed a type I endoleak versus 8 (18%) NM patients (p = 0.02), and 12 (75%) LM patients required a secondary procedure versus 9 (20%) NM patients (p = 0.0002). One (6%) LM patient experienced aneurysm rupture and 2 (13%) other LM patients underwent conversion to open repair. CONCLUSION: Lateral endograft movement within the aneurysm sac at 1 year is associated with increased risk of late adverse events and was at least as good a predictor of these complications as was longitudinal migration.