Atypical mycobacterium detection in refractory chronic rhinosinusitis.

OBJECTIVES: Atypical mycobacterium (AM) involvement in refractory chronic rhinosinusitis (CRS) is sought by some surgeons with customary acid-fast bacilli cultures (AFBC) in the operating room (OR). We evaluate our experience with AM in CRS by describing (1) associated risk factors, (2) species identified, and (3) frequency of positive cultures in clinic versus OR. STUDY DESIGN: Case series with chart review. SETTING: Tertiary rhinology practice. SUBJECTS AND METHODS: AFBC taken between 2005 and 2011 were identified from a microbiology laboratory database. Charts were reviewed for gender, age, medical history, risk factors for AM, pathogen types, and treatments, with statistical comparison using Pearson χ(2). The benefit of "targeted AFBC" for cases with high clinical suspicion was compared with "customary AFBC" in the OR. RESULTS: Thirty-seven patients were identified with AM, of which 10 had one or more risk factors for AM including foreign body (n = 4), non-HIV immune dysfunction (n = 4), and previous chemoradiation (n = 4). Six different AM species were identified: most frequently Mycobacterium abscessus (57.1%), followed by Mycobacterium avium-intracellulare complex (14.3%) and Mycobacterium chelonae (14.3%). "Targeted AFBC" from the outpatient setting were positive in 10 of 190 (5.3%) patients, whereas 10 of 373 (2.6%) patients of "customary AFBC" in the OR were positive (P = .12). Macrolide therapy was employed in 23 of 37 (62%) patients with AM-associated CRS but was not prescribed in patients with positive "customary AFBC" alone. CONCLUSION: AM-associated CRS is an uncommon condition that can occur in the absence of foreign body or overtly altered innate/adaptive immunity. Indications and efficacy of macrolide therapy, as well as the potential relationships between existence of AM in tap water, AM biofilms, and frequent use of nasal irrigations warrant further investigation in refractory CRS.

Oral antifungal therapy for Fusarium-associated chronic rhinosinusitis.

BACKGROUND: Fusarium is commonly reported as an organism found in fungus-associated chronic rhinosinusitis (CRS) yet it is known to be resistant to commonly used antifungal therapies. The goals of this work are to report the incidence of Fusarium-associated CRS in fungal cultures and to describe the treatment experience with oral antifungal agent aimed at this problem. METHODS: Patients with sinus cultures obtained from 2005 through 2008 were retrospectively identified and their medical records were evaluated. Cultures were obtained in patients with recalcitrant rhinosinusitis when purulent discharge was observed. Patient response to the therapy was measured upon the basis of self reported symptom improvements and endoscopic examination. RESULTS: In this 4-year period 2,570 outpatient fungal cultures were obtained and 194 (7.5%) were positive for Fusarium. These 194 positive cultures appeared in 94 individuals. Thirty-four tested positive multiple times. Twenty-three (24.5%) had severe recalcitrant CRS poorly responsive to standard therapies warranting antifungal therapy aimed at Fusarium. Fifteen individuals were treated with voriconazole, 5 with posaconazole, and 3 with both at separate times. Endoscopic evidence of initial improvement on therapy was evident in 16 of 23 patients (69.6%). Of 18 patients who could comment on their experience with the antifungal treatments, nearly 90% of them reported substantial improvement with the therapy. Nine (9/23; 39.1%) were forced to discontinue oral antifungal therapy due to untoward effects. CONCLUSION: Fusarium appears in 7.55% of outpatient cultures of CRS. Of the patients testing positive for Fusarium, 25% received oral antifungal therapy. A positive response was seen in 16 of 23 (69.6%) while receiving other standard therapies. Since Fusarium is not routinely sensitive to commonly used antifungal agents, it warrants special attention.

Evaluating the safety of frontal sinus trephination.

OBJECTIVES/HYPOTHESIS: The depth of the frontal sinus was measured using axial computed tomography (CT) images to examine the safety of frontal sinus trephination at selected distances from the midline. STUDY DESIGN: Review of 200 sinus CT scans. METHODS: Two hundred sinus CT scans (400 frontal sinuses) were reviewed to measure the frontal sinus depth at 5 mm, 10 mm, and 15 mm from midline. RESULTS: Males had a significantly deeper frontal sinus than females at all measurements points (P < .001). The measurements revealed a considerable number of small but nonhypoplastic frontal sinuses, which were shallower than the length of standard frontal trephine instruments (7 mm) and would risk penetration of the posterior table of the sinus. Of all frontal sinuses studied, 9.54% were <7 mm deep at 5 mm from the midline, 10.12% at 10 mm, and 8.96% at 15 mm from the midline. Overall, 15.3% of all frontal sinuses studied had at least one point where the measured depth was <7 mm. CONCLUSIONS: Although the majority of patients have frontal sinuses deep enough to accommodate standard trephine instruments, surgeons should recognize that up to 15% of nonhypoplastic frontal sinuses may not be sufficiently deep at a given point to allow safe trephination without risking unintentional transgression of the posterior table. This study suggests that trephination routinely carried out at a given predetermined distance from the midline may be an unsafe practice. Careful evaluation of the imaging is essential in every case to avoid inadvertent injury and to help select the safest distance from the midline for frontal sinus trephination.

Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix.

Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate the repair and reconstruction of a variety of tissues in clinical and pre-clinical studies. The clinical utility of such scaffolds can be limited by the geometric and mechanical properties of the tissue or organ from which the ECM is harvested. An injectable gel form of ECM could potentially conform to any three-dimensional shape and could be delivered to sites of interest by minimally invasive techniques. The objectives of the present study were to prepare a gel form of ECM harvested from the urinary bladder (urinary bladder matrix or UBM), to characterize the rheological properties of the gel, and finally to evaluate the ability of the gel to support in vitro growth of smooth muscle cells. Following enzymatic solubilization with pepsin, UBM was induced to self-assemble into a gel when brought to physiological conditions. The UBM gel supported the adhesion and growth of rat aortic smooth muscle cells when cultured under static in vitro conditions. The present study showed that an intact form of UBM can be successfully solubilized without purification steps and induced to repolymerize into a gel form of the UBM biologic scaffold material.

The application of tissue engineering procedures to repair the larynx.

The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice, and hearing. The present manuscript describes a study that was conducted in which a biologic scaffold derived from porcine (pig) extracellular matrix (ECM) was used to repair the defect following a hemilaryngectomy procedure in dogs. The ECM-augmented repair was compared with a control standard strap muscle (STM) procedure. The animals were sacrificed after 24 weeks at which time anatomic and histologic analyses were conducted. The ECM repair resulted in a macroscopic and microscopic reconstruction of laryngeal tissue that was superior to that observed with the STM procedure. The importance of regenerated tissue having the same structural and functional characteristics of native tissue is emphasized. A discussion of the mechanisms of ECM remodeling is presented along with the implications of such remodeling in the repair of laryngeal structures.

Efficacy of cidofovir injection for the treatment of recurrent respiratory papillomatosis.

To evaluate the efficacy of intralesional cidofovir injection for the treatment of recurrent respiratory papillomatosis (RRP). It is a prospective, open-label study design. This prospective study included 16 RRP patients, ages 9 to 68 years, who were treated with intralesional injections of cidofovir combined with surgical excision of RRP. The disease states of the patients pretreatment and posttreatment were assessed by assigning RRP severity scores, examining the need for any surgical excision of RRP, and evaluating the presence of RRP upon long-term follow-up. Sixteen patients were treated with cidofovir; however, three were lost to follow-up. Thirteen patients are the subjects of this report. This study group included three pediatric patients. Ten of thirteen patients (76.9%) responded to the treatment and are presently in remission. One patient did not respond, and two patients relapsed after initial success or had a partial response. The responders consisted of eight adults and two children. The mean number of injections the responders received was 3.5, and the average follow-up period of the responders was 25.4 months. No immediate complication of cidofovir treatment was evident. However, three patients were found to have significant vocal fold scarring after long-term follow-up. Cidofovir has been found to be efficacious in treating RRP. Further study regarding long-term follow-up and the assessment of possible side effects after cidofovir intralesional injection for RRP is required.

Development and validation of the voice handicap index-10.

OBJECTIVES/HYPOTHESIS: The objective was to develop an abbreviated voice handicap assessment instrument and compare it with the Voice Handicap Index (VHI). STUDY DESIGN: Item analysis of the VHI in individuals without voice disorders and patients with voice disorders and creation and validation of the abbreviated VHI. METHODS: Clinical consensus review of the VHI items was held to prioritize the clinical value of each of the VHI items (30 items in all). Item analysis of the VHI was performed using the VHI responses of 100 patients with voice problems and 159 control subjects. The 10 most robust VHI items were selected using the item analysis and clinical consensus results to form the Voice Handicap Index-10 (VHI-10). Statistical analysis comparing the validity of the VHI-10 with the VHI was performed with 819 patients representing a wide spectrum of voice disorders. RESULTS: Statistical analysis of the VHI and VHI-10 scores from the study group showed no statistically significant differences between the VHI and the VHI-10. Irrespective of diagnosis, the correlation between the VHI and the VHI-10 was greater than .90 (P = .01). The ratios of the VHI-10 to VHI scores for a variety of voice disorder categories were analyzed and found to be consistently greater than the expected value (33%). This suggests that the VHI-10 may be a more robust instrument than the VHI. CONCLUSION: The VHI-10 is a powerful representation of the VHI that takes less time for the patient to complete without loss of validity. Thus, the VHI-10 can replace the VHI as an instrument to quantify patients' perception of their voice handicap.

A rationally designed genotoxin that selectively destroys estrogen receptor-positive breast cancer cells.

We describe a novel strategy to increase the selective toxicity of genotoxic compounds. The strategy involves the synthesis of bifunctional molecules capable of forming DNA adducts that have high affinity for specific proteins in target cells. It is proposed that the association of such proteins with damaged sites in DNA can compromise protein function and/or DNA repair resulting in increased toxicity. We describe the synthesis of a bifunctional compound consisting of an aniline mustard linked to the 7alpha position of estradiol. This novel compound can form covalent DNA adducts that have high affinity for the estrogen receptor. Breast cancer cells that express high levels of the estrogen receptor showed increased sensitivity to the cytotoxic effects of the new compound.