Faculty Bibliography

OBJECTIVES: To observe the extent of nasal polyposis endoscopically in a cystic fibrosis population before the first surgical intervention and to grade the extent using a modified Malm scale, to observe patients prospectively and record the need for revision endoscopic sinus surgery (ESS), and to compare this among the individual polyp grading groupings. DESIGN: Retrospective medical record review of data collected prospectively. SETTING: Tertiary care hospital. PATIENTS: Forty-nine consecutive patients with a clinical preoperative diagnosis of cystic fibrosis and sinusitis. MAIN OUTCOME MEASURES: Using a modified Malm scale, the extent of polyps was prospectively graded into 3 groups before the first surgical intervention. The number of patients needing revision ESS and the mean time to revision ESS were compared among the 3 groups. RESULTS: Forty-nine consecutive patients underwent ESS between 1992 and 2007. We used a 3-stage system for extent of polyposis: 16 patients were noted to have no polyps (grade A), 14 had mild polyposis (grade B), and 19 had extensive polyposis (grade C). During the study, 14 patients required revision surgery: 3 with mild polyps and 11 with extensive polyps. Mean time to revision surgery was 39.7 months for those with grade B and 23.8 months for those with grade C. In the overall statistical analysis, the rate of revision ESS was significantly different among the 3 groups (P < .001). In pairwise comparisons, there were significant differences between those with grades A and C (P < .001) and between those with grades B and C (P = .04) and a trend toward significance between those with grades A and B (P = .052). There were no complications from ESS. CONCLUSION: Preoperative grading of nasal polyposis in patients with cystic fibrosis can help assess the future likelihood of revision ESS

OBJECTIVE: Endoscopic balloon dilation is increasingly popular as primary therapy for infants with subglottic stenosis. We aim to determine the maximum balloon diameter and pressure where no fracture of the cricoid would occur, minimum balloon size and pressures where a gross fracture of the cricoid occurs, and location of these fractures. We tested these objectives by performing balloon dilation in laryngotracheal complexes of eight euthanized adult male New Zealand white rabbits, with airway characteristics similar to a 3- to 9-month-old infant. METHODS: Subglottic airway diameter of each specimen was determined using endotracheal tubes (Cotton-Myer grading system). Preexistent subglottic disease was excluded by rigid endoscopy. Serial dilation with balloon catheters was performed, employing incremental balloon sizes and pressures, to determine balloon size and pressure, which resulted in a cricoid fracture. Locations of gross fractures were validated by two independent observers. RESULTS: Airway diameter of all specimens was 5.4 mm (size 4.0 endotracheal tube). Four of the seven cricoid cartilages exhibited gross fractures. Dilation with balloon diameters less than 6.0 mm failed to induce a fracture despite maximal inflation to 16.0 atmospheres. The minimum balloon size required to create a fracture was 7.0 mm, at a pressure of 6.0 atmospheres. All fractures occurred at the anterior lamina of cricoid ring. CONCLUSIONS: No fractures occurred when balloon dilation was performed with a balloon 0.6 mm or smaller than the measured subglottic diameter. Fractures of the cricoid occurred when balloon dilation was performed with a balloon 1.6 mm or larger than the subglottic diameter.

OBJECTIVE: Radiotherapy, an essential modality in cancer treatment, frequently induces fibrotic processes in the skin, including accumulation of extracellular matrix. Transforming growth factor-beta is essential in regulating extracellular matrix gene expression and is dependent on Smad3, an intracellular mediator/transcription factor. Our study characterized the genetic expression involved in extracellular matrix accumulation during radiation-induced fibrosis. We performed Smad3 gene silencing in an attempt to abrogate the effects of radiation. STUDY DESIGN: Laboratory research. SETTING: University laboratory. SUBJECTS AND METHODS: C57 murine dermal fibroblasts were irradiated with 20 Gy RNA isolated (0, 6, 12, 24, 48, 72 hours postirradiation) and mRNA analyzed (reverse transcriptase polymerase chain reaction) for known regulators (Smad3, interleukin-13 [IL-13]), tumor necrosis factor-alpha [TNF-alpha]) and mediators of fibrosis (collagen 1A1 [Col1A1]), TGF-beta, matrix metalloprotease-1 and -2 (MMP-1, MMP-2), and tissue inhibitor of metalloprotease-1 (TIMP-1). Smad3 gene expression was silenced using siRNA in an effort to restore an unirradiated gene profile. RESULTS: Following irradiation, there was a steady increase in mRNA expression of Smad3, IL-13, TGF-beta, Col1A1, MMP-2, TIMP-1, with peak at 12 to 24 hours and subsequent decline by 72 hours. TNF-alpha expression remained elevated throughout. MMP-1 showed minimal expression initially, which decreased to negligible by 72 hours. Inhibition of Smad3 significantly decreased expression of Col1A1, TGF-beta, MMP-2, and TIMP-1. IL-13 and TNF-alpha expression was not affected by Smad3 silencing. CONCLUSION: We have characterized the early-phase mRNA expression profiles of the major mediators of radiation-induced fibrosis. Smad3 siRNA effectively abrogated the elevation of Col1A1, TGF-beta, TIMP-1, and MMP-2. IL-13 and TNF-alpha were unaffected by Smad3 silencing and appear to be minor regulators in fibrosis. These findings suggest a therapeutic rationale for Smad3 silencing in vivo

BACKGROUND: Dry mouth is a frequent complaint of adults worldwide. In those who experience dry mouth, therapeutic options include the use of salivary substitutes and sialogogues. METHODS: The authors compared the efficacy and safety of mucoadhesive disks (OraMoist, Axiomedic, Zurich; distributed by Quantum Health, Eugene, Ore.) applied three times daily with those of placebo mucoadhesive disks in a double-masked, randomized, controlled crossover study. The primary end point of interest was within-participant differences in subjective (visual analog scale) ratings of dry mouth according to the New York University Bluestone Mouthfeel Questionnaire. The secondary end point was within-participant differences in salivary flow rates. RESULTS: Twenty-seven participants completed the single-site study. The results showed no significant difference between the two types of mucoadhesive disks, both of which were associated with a statistically significant improvement in the subjective experience of moistness across the 60-minute period after application and compared with baseline measures after two weeks of use. Furthermore, both disks were associated with a statistically significant improvement in salivary flow rates across the 60-minute period after application and compared with baseline measures after one and two weeks of use. The disks were well tolerated, and participants did not report any adverse events. CONCLUSIONS: The mucoadhesive disks used in this study were safe and provided symptomatic relief from dry mouth. Practice Implications. Patients with dry mouth may benefit from this novel delivery system.

BACKGROUND: Acute blood pressure (BP) elevations in neurosurgical patients are associated with serious neurologic, cardiovascular, or surgical site complications. Clevidipine, an ultra-short-acting dihydropyridine calcium antagonist, has been shown to be efficacious and safe for acute hypertension in cardiac surgery. This study assessed the efficacy and safety of clevidipine in controlling perioperative hypertension in the neurosurgical setting. METHODS: Patients scheduled for intracranial surgery were prospectively enrolled after giving consent. Clevidipine (0.5 mg/mL in 20% lipid solution, which was to be initiated at 10 mg/h and titrated to effect) was administered as the primary antihypertensive agent for perioperative hypertension, with target BPs of less than 130 mm Hg. Other vasoactive drugs were administered as needed for treating systolic BP (SBP) less than 90 mm Hg or greater than 130 mm Hg. The primary study endpoint was the proportion of patients not requiring rescue antihypertensives to maintain target SBP (<130 mm Hg). RESULTS: Twenty-two patients were enrolled. One patient did not require antihypertensive therapy. Seventeen patients (17 of 21, 81%) were treated with clevidipine alone; one received clevidipine in the postanesthesia care unit only. Twenty-eight hypertensive episodes (defined as any new acute BP elevation requiring clevidipine initiation) were documented. SBP was reduced to target level within 15 minutes in 22 of 28 episodes (78.6%). Two mild hypotensive episodes occurred after the initiation of clevidipine infusion; these transient decreases in BP were treated with vasoactive drugs and resolved within 5 minutes. CONCLUSIONS: Clevidipine is effective and safe for perioperative hypertension in patients undergoing intracranial procedures. Rapid control of BP is possible with higher starting doses. Drug effects resolved rapidly after drug discontinuation

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is commonly associated with adenotonsillar hypertrophy. We hypothesized that respiratory perturbations extend to other regions of the upper respiratory tract in such children, particularly to rhino-sinus regions. STUDY DESIGN: A prospective case control study using Magnetic Resonance Imaging (MRI) of the upper airway and surrounding tissues of OSAS and controls. Magnetic resonance imaging was used to evaluate radiographic changes within the: paranasal sinuses, middle ear and mastoid air cells, and the nasal passages. RESULTS: We studied 54 OSAS (age 5.7 +/- 3.0 years) and 54 controls (age 6.2 +/- 2.0 years, P = NS). Children with OSAS had significantly more opacification of: maxillary sinuses (P < 0.05), sphenoid sinuses (P < 0.01), and mastoid air cells (P < 0.01). They also had significantly more: middle ear effusions, (P < 0.001), prominence of inferior nasal turbinate(s) (P < 0.05), and deviation of the nasal septum (P < 0.05). CONCLUSIONS: Childhood OSAS is associated with a wide range of upper respiratory tract perturbations and is not limited to adenoid and tonsillar hypertrophy.

Meningitis after cochlear implantation continues to be a concern. Recent studies and anecdotal reports support the belief that intracochlear trauma, lack of appropriate immunizations, and a previously used dual-component electrode predispose patients to a higher rate of contracting meningitis. In addition, a history of meningitis, cochlear dysplasia, and certain variations of surgical technique such as the cochleostomy, very young age, immunocompromise, and the presence of neural prostheses such as shunts, are all potentially predisposing factors. Because many of these factors are beyond our control, there is likely to be an inevitable baseline incidence of meningitis, perhaps related to the underlying deafness, but by controlling other factors, we can hope to minimize the incidence. Despite the efforts of multiple individuals and organizations, there continue to be new cases of meningitis, including a small number of fatalities, each year. There is recent evidence that a sizeable percentage of children with implants have not been vaccinated as suggested by governmental agencies, otolaryngologic societies, implant manufacturers, and many cochlear implant centers. Clearly, efforts must be made to ensure age-appropriate vaccination for all cochlear implant recipients

PURPOSE OF REVIEW: To weigh the clinical impact of new technological insights into heritable thyroid malignancies. RECENT FINDINGS: Medullary thyroid carcinoma and familial nonmedullary thyroid cancers represent the small minority of thyroid cancers that are inherited. New insights into the genetic alterations and molecular mechanisms implicated in these tumors are serving to refine the clinical tools available for their initial diagnosis as well as subsequent follow-up. In addition to an analysis of rearranged during transfection mutations and calcitonin profiles in medullary thyroid carcinoma, this review includes emphasis on familial nonmedullary thyroid cancer syndromes, including genetic findings in familial papillary thyroid cancer, familial adenomatous polyposis, Cowden syndrome, Carney complex, and Werner syndrome. SUMMARY: Genetic mutational information is increasingly available on medullary and familial nonmedullary thyroid cancer and their associated syndromes. The clinical significance of this information for affected patients and their families continues to undergo evaluation