Faculty Bibliography

Trigeminal-specific stimulants have been shown to activate different receptors preferentially and this likely accounts for variation in sensory perception. It is unclear whether trigeminal sensitivity is similar across different transient receptor potential (TRP) receptors or if dysfunction of different receptors results in differing patient symptoms. Therefore, a prospective cohort study was conducted, consisting of trigeminal lateralization testing with three different stimulants (eucalyptol, isothiocyanate, acetic acid), olfaction testing with Sniffin' Sticks, and measurement of various patient-reported outcome measures (PROMs). A total of 50 participants were enrolled across the olfactory spectrum. Mean TDI score was 27.1 ± 8.3 (range 7.0-39.5) with 38% normosmic and 62% dysosmic. Mean trigeminal lateralization scores out of 20 in the overall cohort were 16.18 (2.78) for eucalyptol, 14.94 (3.49) for mustard oil, and 15.28 (3.68) for vinegar. Eucalyptol showed a significant correlation with threshold scores of Sniffin' Sticks. A significant correlation was found between acetic acid and various PROMs. None of the lateralization scores of the trigeminal stimulants correlated to each other significantly and there was no correlation to age. The lack of correlation suggests that the measured sensitivity of one type of TRP receptor may not translate to similar sensitivity of the other receptors. Additional investigations with TRPV1 and TRPA1 agonists are needed to corroborate our findings.

A virtual workshop was organized by the Heart Valve Collaboratory to identify areas of expert consensus, areas of disagreement, and evidence gaps related to bioprosthetic aortic valve hemodynamics. Impaired functional performance of bioprosthetic aortic valve replacement is associated with adverse patient outcomes; however, this assessment is complicated by the lack of standardization for labelling, definitions, and measurement techniques, both after surgical and transcatheter valve replacement. Echocardiography remains the standard assessment methodology because of its ease of performance, widespread availability, ability to do serial measurements over time, and correlation with outcomes. Management of a high gradient after replacement requires integration of the patient's clinical status, physical examination, and multimodality imaging in addition to shared patient decisions regarding treatment options. Future priorities that are underway include efforts to standardize prosthesis sizing and labelling for both surgical and transcatheter valves as well as trials to characterize the consequences of adverse hemodynamics.

The aim of this multicenter retrospective study is to characterize the histopathologic features of initial/early biopsies of proliferative leukoplakia (PL; also known as proliferative verrucous leukoplakia), and to analyze the correlation between histopathologic features and malignant transformation (MT). Patients with a clinical diagnosis of PL who have at least one biopsy and one follow-up visit were included in this study. Initial/early biopsy specimens were reviewed. The biopsies were evaluated for the presence of squamous cell carcinoma (SCCa), oral epithelial dysplasia (OED), and atypical verrucous hyperplasia (AVH). Cases that lacked unequivocal features of dysplasia were termed "hyperkeratosis/parakeratosis not reactive (HkNR)". Pearson chi-square test and Wilcoxon test were used for statistical analysis. There were 86 early/initial biopsies from 59 patients; 74.6% were females. Most of the cases had a smooth/homogenous (34.8%) or fissured appearance (32.6%), and only 13.0% had a verrucous appearance. The most common biopsy site was the gingiva/alveolar mucosa (40.8%) and buccal mucosa (25.0%). The most common histologic diagnosis was OED (53.5%) followed by HkNR (31.4%). Of note, two-thirds of HkNR cases showed only hyperkeratosis and epithelial atrophy. A lymphocytic band was seen in 34.8% of OED cases and 29.6% of HkNR cases, mostly associated with epithelial atrophy. Twenty-eight patients (47.5%) developed carcinoma and 28.9% of early/initial biopsy sites underwent MT. The mortality rate was 11.9%. Our findings show that one-third of cases of PL do not show OED with most exhibiting hyperkeratosis and epithelial atrophy, but MT nevertheless occurred at such sites in 3.7% of cases.

BACKGROUND:Otologic symptoms consistent with Eustachian tube dysfunction (ETD) are common in patients with chronic rhinosinusitis (CRS), but can also occur independently of CRS as primary ETD. It is unclear if CRS+ETD is similar to primary ETD or how treatment outcomes compare. METHODS:A systematic search of PubMed, CINAHL, Scopus, and Cochrane Library was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Any study describing ETD in CRS was included. Primary ETD studies were limited to those with preoperative and postoperative Eustachian Tube Dysfunction Questionnaire (ETDQ-7) scores in ETD treated only with Eustachian tube balloon dilation (ETBD). RESULTS:Sixteen studies were included: nine studies with 1336 consecutive patients with CRS and seven studies with 161 patients with primary ETD. In studies with specific data, 225 (47.2%) patients with CRS had a score >14.5, consistent with ETD. In CRS+ETD, baseline mean ± standard deviation (SD) ETDQ-7 score was 20.7 ± 8.4 and did not differ by polyp status. In primary ETD, mean ETDQ-7 score was significantly higher than CRS+ETD (29.5 ± 8.1, p < 0.0001). Regarding treatment outcomes, CRS+ETD treated with endoscopic sinus surgery (ESS) alone resulted in mean ETDQ-7 in the normal range (13.2 ± 5.3), with a mean change of -7.4 (95% confidence interval [CI], -10.82 to -3.99) (p < 0.00001). Patients with primary ETD treated with ETBD had postoperative ETDQ7 scores of 14.9 ± 7.5 with mean change of -13.9 (95% CI, -18.01 to -9.88), p < 0.00001. CONCLUSION:ETD is noted in approximately half of patients with CRS. Outcomes of CRS+ETD treated with ESS alone are similar to those of patients with primary ETD treated with ETBD.

Histone deacetylase 4 (Hdac4) is known to control chondrocyte hypertrophy and bone formation. We have previously shown that parathyroid hormone (PTH) regulates many aspects of Hdac4 function in osteoblastic cells in vitro; however, in vivo confirmation was previously precluded by pre-weaning lethality of the Hdac4 deficient mice. To analyze the function of Hdac4 in bone in mature animals, we generated mice with osteoblast lineage-specific knockout of Hdac4 (Hdac4^ob-/-) by crossing transgenic mice expressing Cre recombinase under the control of a 2.3kb fragment of the Col1a1 promoter with mice bearing loxP-Hdac4. The Hdac4^ob-/-mice survive to adulthood and developed a mild skeletal phenotype. At 12 weeks of age, they had short, irregularly-shaped and stiff tails due to smaller tail vertebrae, with almost no growth plates. The tibial growth plate zone was also thinned and Mmp13 and Sost mRNAs were increased in the distal femurs of Hdac4^ob-/-mice. Immunohistochemistry showed that sclerostin was elevated in Hdac4^ob-/-mice, suggesting that Hdac4 inhibits its gene and protein expression. To determine the effect of PTH in these mice, hPTH (1-34) or saline were delivered for 14 days with subcutaneously implanted devices in 8-week-old female Hdac4^ob-/-and wild type (Hdac4^fl/fl) mice. Serum CTX, a marker of bone resorption, was increased in Hdac4^ob-/-mice with or without PTH treatment. Tibial cortical BV/TV, Ct.Th, and relative cortical area (RCA) were decreased in Hdac4^ob-/-mice but PTH caused no further decrease in Hdac4^ob-/-mice. Tibial trabecular BV/TV and thickness were not changed significantly in Hdac4^ob-/-mice but decreased with PTH treatment. These results indicate that Hdac4 inhibits bone resorption and has anabolic effects via inhibiting Mmp13 and Sost/sclerostin expression. Hdac4 influences cortical bone mass and thickness and knockout of Hdac4 prevents the catabolic effect of PTH in cortical bone.