Hearing Loss Is Associated with Increased Variability in Double Support Period in the Elderly.

Hearing loss is a disabling condition that increases with age and has been linked to difficulties in walking and increased risk of falls. The purpose of this study is to investigate changes in gait parameters associated with hearing loss in a group of older adults aged 60 or greater. Custom-engineered footwear was used to collect spatiotemporal gait data in an outpatient clinical setting. Multivariable linear regression was used to determine the relationship between spatiotemporal gait parameters and high and low frequency hearing thresholds of the poorer hearing ear, the left ear, and the right ear, respectively, adjusting for age, sex, race/ethnicity, and the Dizziness Handicap Inventory-Screening version score. Worsening high and low frequency hearing thresholds were associated with increased variability in double support period. Effects persisted after adjusting for the effects of age and perceived vestibular disability and were greater for increases in hearing thresholds for the right ear compared to the left ear. These findings illustrate the importance of auditory feedback for balance and coordination and may suggest a right ear advantage for the influence of auditory feedback on gait.

Ectopic Parathyroid Adenoma of the Piriform Sinus on Parathyroid 4D-CT and 99mTc-MIBI SPECT/CT.

Ectopic parathyroid adenomas are a common cause of postsurgical persistent primary hyperparathyroidism. Our case highlights a patient with a negative bilateral 4-gland exploration with follow-up parathyroid 4-dimensional CT and Tc-MIBI SPECT/CT, yielding focal uptake in the right piriform sinus. Subsequent direct laryngoscopy revealed a mass in the piriform sinus, which was resected with surgical pathology yielding parathyroid adenoma.

Trends of Follow-Up Recommendations Made on Musculoskeletal MRI Reports.

OBJECTIVE. The purpose of this article was to analyze trends in follow-up recommendations made on musculoskeletal MRI reports. MATERIALS AND METHODS. An IRB-approved retrospective study identified 790 musculoskeletal MRI reports from our database between January 1, 2016, and January 1, 2018, containing follow-up recommendations made by the interpreting radiologist. Metadata were automatically extracted and classification of the recommendations was performed by manual review. Clinical outcome data were collected from the electronic health record. After exclusion criteria were applied, 654 reports were included in the study. Descriptive statistics, Fisher exact tests, and chi-square tests were used for analysis. RESULTS. Clinicians acknowledged 83% and followed 73% of the recommendations. Follow-up compliance varied with the type of recommendation made: 98% for clinical intervention versus 67% for additional imaging (p < 0.001). Subspecialties acknowledged and followed recommendations at different rates: 92% and 85% for internists versus 76% and 64% for orthopedists (p < 0.001 and p < 0.001), respectively. Patient age, practice setting, radiologist experience, recommendation conditionality, and specified follow-up time intervals made no difference in compliance rate (all p > 0.05). There was no difference in compliance rate among various pathologic findings of concern (p = 0.995). Compliance rate increased significantly after direct communication between the radiologist and clinician compared with when there was no direct communication (93% vs 71%, p < 0.001). Concern for neoplasm comprised the greatest number of unacknowledged recommendations (73%). CONCLUSION. Musculoskeletal MRI recommendations are followed independent of the finding of concern and compliance is lowest for requests of additional imaging. Direct communication improves compliance and may be particularly helpful for orthopedic referrers.

Prognostic and theranostic 18F-FDG PET biomarkers for anti-PD1 immunotherapy in metastatic melanoma: association with outcome and transcriptomics.

PURPOSE: An imaging-based stratification tool is needed to identify melanoma patients who will benefit from anti Programmed Death-1 antibody (anti-PD1). We aimed at identifying biomarkers for survival and response evaluated in lymphoid tissue metabolism in spleen and bone marrow before initiation of therapy. METHODS: This retrospective study included 55 patients from two institutions who underwent 18F-FDG PET/CT before anti-PD1. Parameters extracted were SUVmax, SUVmean, HISUV (SUV-based Heterogeneity Index), TMTV (total metabolic tumor volume), TLG (total lesion glycolysis), BLR (Bone marrow-to-Liver SUVmax ratio), and SLR (Spleen-to-Liver SUVmax ratio). Each parameter was dichotomized using the median as a threshold. Association with survival, best overall response (BOR), and transcriptomic analyses (NanoString assay) were evaluated using Cox prediction models, Wilcoxon tests, and Spearman's correlation, respectively. RESULTS: At 20.7 months median follow-up, 33 patients had responded, and 29 patients died. Median PFS and OS were 11.4 (95%CI 2.7-20.2) and 28.5 (95%CI 13.4-43.8) months. TMTV (>25cm3), SLR (>0.77), and BLR (>0.79) correlated with shorter survival. High TMTV (>25 cm3), SLR (>0.77), and BLR (>0.79) correlated with shorter survival, with TMTV (HR PFS 2.2, p = 0.02, and HR OS 2.5, p = 0.02) and BLR (HR OS 2.3, p = 0.04) remaining significant in a multivariable analysis. Low TMTV and TLG correlated with BOR (p = 0.03). Increased glucose metabolism in bone marrow (BLR) was associated with transcriptomic profiles including regulatory T cell markers (p < 0.05). CONCLUSION: Low tumor burden correlates with survival and objective response while hematopoietic tissue metabolism correlates inversely with survival. These biomarkers should be further evaluated for potential clinical application.

Poorly Differentiated Primary Carcinoma of the Middle Ear on 18F-FDG PET/CT.

Primary carcinoma of the middle ear is extremely rare. A 41-year-old woman with a history of skull base osteomyelitis and chronic suppurative right otitis media presented with 1 month of right-sided facial droop, tearing, and headaches. Initial head CT revealed bony destruction and soft tissue opacification involving the right middle ear. Surgical biopsy yielded poorly differentiated carcinoma. Subsequent F-FDG PET/CT and MRI scans demonstrated FDG-avid soft tissue in the right middle ear with associated heterogeneously enhancing soft tissue on MRI.

Dizziness Handicap Inventory Score Is Highly Correlated With Markers of Gait Disturbance.

OBJECTIVE: To evaluate the association between Dizziness Handicap Inventory-Screening version (DHI-S) score and spatiotemporal gait parameters using SoleSound, a newly developed, inexpensive, portable footwear-based gait analysis system. STUDY DESIGN: Cross-sectional. PATIENTS: One hundred eighteen patients recruited from otology clinic. INTERVENTION(S): Subjects completed the DHI-S survey and four uninterrupted walking laps wearing SoleSound instrumented footwear on a hard, flat surface for 100 m. MAIN OUTCOME MEASURE(S): For each subject, mean and coefficient of variation (CV) of stride length, cadence, walking speed, foot-ground clearance, double-support time, swing period, and stance-to-swing were computed by considering 40 strides of steady-state walking within each lap. Linear regression models were employed to study correlations between these variables and DHI-S scores after adjusting for age, sex, and race/ethnicity. RESULTS: Patients with higher DHI-S score took shorter steps and less steps per minute (-0.017 m and -1.1 steps/min per every four-point increase in DHI-S score, p < 0.05) than patients with a lower DHI-S score, with slower walking speed (-0.025 m/s per every four-point increase in DHI-S score, p < 0.01). Additionally, patients with higher DHI-S scores showed larger variability in all analyzed temporal parameters (+0.1% for CV of cadence, +0.5% for CV of double support period, +0.2% for CV of swing period, and +0.4% for CV of stance-to-swing, per every four-point increase in DHI-S score, p < 0.01). CONCLUSION: SoleSound was effective in measuring a wide range of gait parameters. Patients' self-perception of vestibular handicap, as assessed with DHI-S, is associated with deterioration in measurable gait parameters independent of age.

Reduction of the Harmonic Series Influences Musical Enjoyment With Cochlear Implants.

OBJECTIVE: Cochlear implantation is associated with poor music perception and enjoyment. Reducing music complexity has been shown to enhance music enjoyment in cochlear implant (CI) recipients. In this study, we assess the impact of harmonic series reduction on music enjoyment. STUDY DESIGN: Prospective analysis of music enjoyment in normal-hearing (NH) individuals and CI recipients. SETTING: Single tertiary academic medical center. PATIENTS: NH adults (N = 20) and CI users (N = 8) rated the Happy Birthday song on three validated enjoyment modalities-musicality, pleasantness, and naturalness. INTERVENTION: Subjective rating of music excerpts. MAIN OUTCOME MEASURES: Participants listened to seven different instruments play the melody, each with five levels of harmonic reduction (Full, F3+F2+F1+F0, F2+F1+F0, F1+F0, F0). NH participants listened to the segments both with and without CI simulation. Linear mixed effect models (LME) and likelihood ratio tests were used to assess the impact of harmonic reduction on enjoyment. RESULTS: NH listeners without simulation rated segments with the first four harmonics (F3+F2+F1+F0) most pleasant and natural (p <0.001, p = 0.004). NH listeners with simulation rated the first harmonic alone (F0) most pleasant and natural (p <0.001, p = 0.003). Their ratings demonstrated a positive linear relationship between harmonic reduction and both pleasantness (slope estimate = 0.030, SE = 0.004, p <0.001, LME) and naturalness (slope estimate = 0.012, SE = 0.003, p = 0.003, LME). CI recipients also found the first harmonic alone (F0) to be most pleasant (p = 0.003), with a positive linear relationship between harmonic reduction and pleasantness (slope estimate = 0.029, SE = 0.008, p <0.001, LME). CONCLUSION: Harmonic series reduction increases music enjoyment in CI and NH individuals with or without CI simulation. Therefore, minimization of the harmonics may be a useful strategy for enhancing musical enjoyment among both NH and CI listeners.

Eradicating acute myeloid leukemia in a Mll(PTD/wt):Flt3(ITD/wt) murine model: a path to novel therapeutic approaches for human disease.

The coexpression of the MLL partial tandem duplication (PTD) and the FLT3 internal tandem duplication (ITD) mutations associate with a poor outcome in cytogenetically normal acute myeloid leukemia (AML). In mice, a double knock-in (dKI) of Mll(PTD/wt) and Flt3(ITD/wt) mutations induces spontaneous AML with an increase in DNA methyltransferases (Dnmt1, 3a, and 3b) and global DNA methylation index, thereby recapitulating its human AML counterpart. We determined that a regulator of Dnmts, miR-29b, is downregulated in bone marrow of dKI AML mice. Bortezomib exerted a dose-dependent increase in miR-29b expression in AML blasts ex vivo, followed by decreased Dnmts, reduced proliferation, and increased apoptosis. In vivo, bortezomib was not active against dKI AML, yet liposomal-encapsulated bortezomib, as a single agent, reversed downregulation of miR-29b in vivo and induced a long-term (90-day) disease-free remission in 80% of dKI AML mice that exhibited high leukemic burden at the start of therapy, yet showed no signs of relapse at autopsy. Taken together, these data support that liposomal bortezomib, as a single agent, eradicates Mll(PTD/wt):Flt3(ITD/wt) AML in mouse and may represent a powerful and potentially curative approach to high-risk human disease.