Lohse, Christine M.

AbstractObjectiveTo characterize normative adult ranges for cochlear promontory thickness relevant to the development of subendosteal and transpromontory electrodes to rehabilitate various neurotologic disorders.PatientsAdults (≥18 years).InterventionIn vivo radiologic assessment using a 192‐slice CT scanner (Force‐192; Siemens Healthcare) with ultrahigh‐resolution scan mode combined and iterative reconstruction.Main Outcome MeasureCochlear promontory thickness.ResultsAmong 48 included patients (96 ears), the mean (SD) age was 56 (18) years (range 25–94) and included 25 (52%) women. Of that 12 patients (25%) had osteopenia (n = 6) or osteoporosis (n = 6). The mean (SD) body mass index was 28 (5) kg/m2. The mean (SD) promontory thickness for the 96 temporal bones under study was 1.22 (0.24) mm (range 0.55–1.85). There was not a statistically significant association between age and promontory thickness (correlation coefficient .08; p = .44). Promontory thickness was significantly greater for men than women (mean 1.28 vs. 1.17 mm; p = .03) and increased with increasing body mass index (correlation coefficient .30; p = .004). Last, promontory thickness was significantly less for patients with osteopenia or osteoporosis compared with those without these conditions (mean 1.09 vs. 1.27 mm; p = .002).ConclusionsCochlear promontory thickness can vary by almost 1.5 mm across patients and is significantly associated with patient sex, body mass index, and comorbid osteopenia/osteoporosis. Subendosteal and transpromontory electrode placement techniques must account for this degree of variability.Level of EvidenceIV

Context.— Epithelioid angiomyolipomas (eAMLs) are rare tumors of the kidney that occur in patients with tuberous sclerosis complex or in a sporadic setting; a subset of these tumors exhibit metastatic behavior. Objective.— To analyze molecular profiling data to identify pathogenic alterations in rare cases of metastatic eAML, and to identify immunohistochemistry (IHC)-based surrogate markers. Design.— Molecular profiling data from the American Association for Cancer Research GENIE registry was accessed for 23 patients with angiomyolipomas, and 9 of 16 patients with eAMLs in our institutional registry were evaluated with next-generation sequencing. IHC was performed to screen for alterations of P53, RB, and ATRX for all 16 institutional cases. Results.— Combined alterations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1) were identified using next-generation sequencing in 7 of 8 (88%) patients with metastatic disease compared to a single patient with nonmetastatic disease (RB1 variant of uncertain significance; 1 of 24, 4%). No cases with abnormal IHC results were identified in 11 patients with nonmetastatic disease compared to 3 of 5 patients with metastatic disease. Conclusions.— Our results show that the majority of metastatic eAMLs have mutations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1), while these are rare in patients with nonmetastatic disease. Furthermore, IHC for P53, RB, and ATRX may serve as a screen for a subset of these alterations in resource-limited settings. These findings, if validated in larger data sets, have the potential to predict metastatic behavior in eAMLs.

Objective Management of small vestibular schwannoma (VS) remains controversial, as patients are typically candidates for all three management options including microsurgery, stereotactic radiosurgery, or wait-and-scan. This study compares patient satisfaction across treatment modalities in patients with small VS. Study Design Cross-sectional study. Setting Survey distributed to members of the Acoustic Neuroma Association and Mayo Clinic patients. Methods Patients with small (<1 cm in any location) sporadic VS who completed at least one survey regarding treatment history and patient satisfaction were included. Results Among 346 patients with small VS, 106 (31%) underwent microsurgery, 78 (23%) radiosurgery, 152 (44%) wait-and-scan, and 10 (3%) multimodal treatment. Collectively, 307 (89%) patients indicated “Yes, I am happy with my treatment type and in hindsight I would not change anything,” and 39 (11%) indicated “No, in hindsight I would have chosen a different treatment type.” Satisfaction differed significantly by treatment group with 85, 86, 96, and 40% of patients in the microsurgery, radiosurgery, wait-and-scan, and multimodal groups reporting that they were satisfied with treatment, respectively (p < 0.001). Satisfaction also differed significantly among those undergoing upfront treatment with microsurgery or radiosurgery (81%), initial wait-and-scan followed by treatment (88%), and wait-and-scan only groups (96%; p = 0.001). Specifically, the wait-and-scan only group demonstrated greater satisfaction compared with the other two treatment strategies (p < 0.05 for both). Conclusions Patient satisfaction with the management of small VS is generally high. Management with wait-and-scan, even if treatment is eventually pursued, may offer higher patient satisfaction compared with upfront treatment.

Objective To assess quality-of-life (QoL) outcomes after modified subtotal petrosectomy with ear canal closure (mSTP) for chronic otitis media. Study Design Survey study. Setting Tertiary referral center. Patients Patients with chronic otitis media. Interventions mSTP. Main Outcome Measures Survey results from enrolled patients on the validated disease-specific Chronic Ear Survey (CES) and Chronic Otitis Media Outcome Test-15 (COMOT-15) regarding their current state of health and, if surgery was performed within 3 years of enrollment, their state of health before mSTP. Results A total of 23 patients were studied, including 19 who underwent surgery within 3 years of enrollment. Postoperatively, mean total CES scores were 80 and COMOT-15 scores were 41, with a higher CES and a lower COMOT-15 indicating better QoL. There were statistically significant improvements after mSTP in the CES activity restriction (25% difference; p = 0.008), symptom (17% difference; p = 0.007), and medical resource (13% difference; p = 0.03) domain and total (18% difference; p = 0.006) scores. In addition, there were statistically significant improvements in the COMOT-15 ear symptom (−22% difference; p < 0.001) domain and total (−16% difference; p = 0.01) scores; however, improvements in the hearing function and mental health domains did not achieve statistical significance. Postoperative COMOT-15 total scores were significantly better for patients who underwent aural rehabilitation compared to those who did not (−17% difference; p < 0.001). Conclusion Modified subtotal petrosectomy with ear canal closure is a useful intervention for patients with recalcitrant chronic otitis media, offering improved QoL in appropriately selected patients. Aural rehabilitation, when feasible, provides the potential for further QoL improvement.

OBJECTIVE Facial nerve function, hearing preservation, and tumor control have been the primary benchmarks used to assess vestibular schwannoma (VS) outcomes. Acknowledging the frequent discrepancy between what physicians prioritize and what patients value, there has been increasing prioritization of patient-reported outcome measures when evaluating the impact of VS diagnosis and its treatment. Motivated by reported limitations of prior instruments used to assess quality of life (QOL) in patients with VS, the authors describe the development and validation of a new disease-specific QOL measure: the Vestibular Schwannoma Quality of Life (VSQOL) Index. METHODS The content development phase comprised identification of clinically important domains and prioritization of feelings or concerns individuals with VS may have. The validation phase encompassed determining how items were grouped into domains and eliminating redundant items. Both phases leveraged data from cross-sectional and longitudinal surveys, expertise from a multidisciplinary working group, and patients with a broad range of experiences with VS (n = 42 during content development and n = 263 during validation). Domain scores from the new instrument were assessed for reliability and correlation with other measures of similar constructs. RESULTS The VSQOL Index consists of 40 items that evaluate the impact of VS diagnosis and its management on QOL, treatment satisfaction, and employment and is estimated to take 8–10 minutes to complete. Domain scores range from 0 (worst) to 100 (best) and demonstrate excellent psychometric properties, including content, construct, and convergent validity and both internal consistency (Cronbach’s alphas 0.83 to 0.91) and test-retest reliability (reliability coefficients 0.86 to 0.96). CONCLUSIONS The VSQOL Index is a valid and reliable measure that overcomes several limitations of prior instruments, including omission or underrepresentation of domains that frequently impact well-being, such as pain, cognition, satisfaction or regret surrounding treatment decisions, and occupational limitations, to comprehensively evaluate the impact of VS diagnosis or its treatment on QOL.

Abstract The aim of this cross‐sectional study was to examine whether a history of selective estrogen receptor modifiers (SERMs), tamoxifen and raloxifene, use was associated with cognitive performance, odds of mild cognitive impairment (MCI), or magnetic resonance imaging (MRI) markers of neurodegeneration associated with Alzheimer's disease. We included women with prior history of breast cancer or no prior history of any cancer at enrollment in the Mayo Clinic Study of Aging (MCSA). This information was abstracted using the Rochester Epidemiology Project medical‐linkage system. Logistic regression was used to examine associations of SERMs with odds of MCI. Linear regression models were used to examine associations of SERMs with cognitive z‐scores (Memory, Executive Function, Language, Visuospatial Skills, Global Cognition), and MRI markers. Among 2840 women aged 50 and older in the MCSA, 151 had a history of breast cancer, and 42 (28%) of these had a history of tamoxifen treatment. A total of 2235 women had no prior history of any cancer, and 76 (3%) of these had a history of raloxifene use. No significant associations between tamoxifen use and cognition, or odds of MCI were observed among women with a history of breast cancer after adjusting for confounders. Similarly, raloxifene use was not significantly associated with cognition, or odds of MCI in women without a history of cancer after adjusting for confounders. We did not find significant associations between the use of either SERM and MRI markers. Use of tamoxifen or raloxifene was not significantly associated with cognition in postmenopausal women.

Objective Spontaneous tumor shrinkage during wait-and-scan management of sporadic vestibular schwannoma is generally considered an uncommon phenomenon. However, most data informing this understanding stem from single-slice linear tumor measurements taken in the axial imaging plane. The objective of the current work was to characterize the regression capacity of sporadic vestibular schwannomas using volumetric tumor measurements. Study Design Retrospective cohort study using slice-by-slice, three-dimensional volumetric tumor measurements. Setting Three tertiary referral centers. Patients Patients with sporadic vestibular schwannoma. Interventions Wait-and-scan. Main Outcome Measures Regression-free survival rates with regression defined as a decrease of at least 20% of the tumor volume. Results Among 952 patients undergoing a total of 3,505 magnetic resonance imaging studies during observation, 123 experienced volumetric tumor regression after diagnosis at a median of 1.2 years (interquartile range, 0.6–2.9 yr). Volumetric regression-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (92–95%; 662), 86% (83–89%; 275), and 78% (73–82%; 132), respectively. Among 405 patients who demonstrated an initial period of tumor growth but continued wait-and-scan management, 48 experienced volumetric regression at a median of 1.2 years (interquartile range, 0.8–2.6 yr) after initial growth. Volumetric regression-free survival rates at 1, 3, and 5 years after initial growth were 94% (92–97%; 260), 84% (79–89%; 99), and 75% (67–83%; 43), respectively. Ultimately, only 82 of the 952 patients studied showed exclusively volumetric tumor regression (i.e., without any periods of tumor growth) by the time of last follow-up. Conclusion Spontaneous volumetric tumor shrinkage during wait-and-scan management occurs more frequently than suggested by previous studies using linear tumor measurements and can even occur after previous episodes of documented tumor growth. These data further highlight the dynamic nature of vestibular schwannoma growth. To this end, the application of natural history data to patient management requires a nuanced approach that parallels the complex tumor behavior of vestibular schwannoma.

Objective To characterize current awareness, perceptions, and literacy surrounding hearing loss among United States primary healthcare professionals. Study design National cross-sectional survey study. Setting United States. Participants Four hundred six healthcare professionals. Results Survey respondents included 205 primary care physicians and 201 nurse practitioners or physician assistants. When compared with 10 other common health conditions, only 1% of respondents ranked hearing loss as a “most important” health condition to manage. Less than half of providers reported recommending hearing testing for their patients at least once per year, whereas evaluation of blood pressure, total cholesterol, body mass index, and blood glucose levels are recommended at least annually by more than 80% of providers. Although 95% of respondents indicated that it is somewhat important or very important for patients to know the standard definition for normal hearing, only 57% of surveyed providers know of a standard definition themselves, and only 28% reported familiarity with the concept of “20/20 hearing.” Conversely, more than 80% of respondents know the “normal” metric for blood pressure, total cholesterol, body mass index, blood glucose, and vision. Most respondents realize that hearing is important to overall health and hearing loss can impact personal safety, lead to social isolation, and negatively impact quality of life. Fifty-four percent also acknowledged a link between hearing loss and depression, but a majority were not very aware of the relationship of hearing loss to risk of falling and dementia, reduced income and job opportunities, and type 2 diabetes. Importantly, only 40% of providers believe hearing loss is treatable, and only 17% believe it is preventable. Conclusion Despite widespread literacy of what constitutes normal blood pressure, total cholesterol, body mass index, blood glucose, and vision metrics, healthcare providers exhibit a poor understanding of normal hearing levels. Few providers prioritize hearing health or regularly recommend for annual hearing evaluation. Most providers believe that options for people with hearing loss are limited, which may have important implications for prioritizing discussion of hearing loss with patients.

Abstract Alterations in nuclear structure distinguish cancer cells from noncancer cells. These nuclear alterations can be translated into quantifiable features by digital image analysis in a process known as quantitative nuclear morphometry. Recently, quantitative nuclear morphometry has been shown to predict metastasis and biochemical recurrence of prostate cancer. However, little is known about the cellular mechanisms underlying these nuclear morphometric changes. Alterations of nuclear matrix proteins are frequently involved in changes of nuclear structure. A number of co-activators interact with these nuclear structure–related proteins, suggesting that they might be involved in quantitative nuclear morphometry changes. We have shown previously that the transcriptional co-activator p300 is involved in prostate cancer progression. However, the ability of a transcriptional regulator like p300 to modulate nuclear morphology has not been described previously. In the present study, we show that p300 expression in prostate cancer biopsy tissue from 95 patients correlates with quantifiable nuclear alterations. Moreover, we show that transfection of p300 into prostate cancer cells in culture induces quantifiable nuclear alterations, such as diameter, perimeter, and absorbance among others, as assessed by digital image analysis. These alterations correlate individually with aggressive features in prostate cancer, such as expression of the proliferation marker Ki-67 and extraprostatic extension of the tumor. Finally, we found that transfection of p300 into prostate cancer cells specifically increases mRNA and protein levels of nuclear matrix peptides lamins A and C, suggesting that these proteins mediate the p300-induced effects. These findings reveal a new insight into the transcriptional and structural regulation of prostate cancer.