Faculty Bibliography

OBJECTIVE: To describe our initial operative experience and hearing preservation results with the Advanced Bionics (AB) Mid Scala Electrode (MSE). STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Sixty-three MSE implants in pediatric and adult patients were compared with age- and sex-matched 1j electrode implants from the same manufacturer. All patients were severe to profoundly deaf. INTERVENTION: Cochlear implantation with either the AB 1j electrode or the AB MSE. MAIN OUTCOME MEASURES: The MSE and 1j electrodes were compared in their angular depth of insertion and pre to postoperative change in hearing thresholds. Hearing preservation was analyzed as a function of angular depth of insertion. Secondary outcome measures included operative time, incidence of abnormal intraoperative impedance and telemetry values, and incidence of postsurgical complications. RESULTS: Depth of insertion was similar for both electrodes, but was more consistent for the MSE array and more variable for the 1j array. Patients with MSE electrodes had better hearing preservation. Thresholds shifts at four audiometric frequencies ranging from 250 to 2000 Hz were 10, 7, 2, and 6 dB smaller for the MSE electrode than for the 1j (p < 0.05). Hearing preservation at low frequencies was worse with deeper insertion, regardless of array. Secondary outcome measures were similar for both electrodes. CONCLUSION: The MSE electrode resulted in more consistent insertion depth and somewhat better hearing preservation than the 1j electrode. Differences in other surgical outcome measures were small or unlikely to have a meaningful effect.

We investigated vestibular function and otolith size (OS) in larvae of white seabass Atractoscion nobilis exposed to high partial pressure of CO2 (pCO(2)) The context for our study is the increasing concentration of CO2 in seawater that is causing ocean acidification (OA). The utricular otoliths are aragonitic structures in the inner ear of fish that act to detect orientation and acceleration. Stimulation of the utricular otoliths during head movement results in a behavioral response called the vestibulo-ocular reflex (VOR). The VOR is a compensatory eye rotation that serves to maintain a stable image during movement. VOR is characterized by gain (ratio of eye amplitude to head amplitude) and phase shift (temporal synchrony). We hypothesized that elevated pCO(2) would increase OS and affect the VOR. We found that the sagittae and lapilli of young larvae reared at 2500 mu atm pCO(2) (treatment) were 14 to 20% and 37 to 39% larger in area, respectively, than those of larvae reared at 400 mu atm pCO(2) (control). The mean gain of treatment larvae (0.39 +/- 0.05, n = 28) was not statistically different from that of control larvae (0.30 +/- 0.03, n = 20), although there was a tendency for treatment larvae to have a larger gain. Phase shift was unchanged. Our lack of detection of a significant effect of elevated pCO(2) on the VOR may be a result of the low turbulence conditions of the experiments, large natural variation in otolith size, calibration of the VOR or mechanism of acid-base regulation of white seabass larvae.

For bilateral cochlear implant (CI) patients, electrodes that receive the same frequency allocation often stimulate locations in the left and right ear that do not yield the same perceived pitch, resulting in a pitch mismatch. This pitch mismatch may be related to degraded binaural abilities. Pitch mismatches have been found for some bilateral CI users and the goal of this study was to determine whether pitch mismatches are prevalent in bilateral CI patients, including those with extensive experience with bilateral CIs. To investigate this possibility, pitch matching was conducted with 16 bilateral CI patients. For 14 of the 16 participants, there was a significant difference between those electrodes in the left and right ear that yielded the same pitch and those that received the same frequency allocation in the participant's clinical map. The results suggest that pitch mismatches are prevalent with bilateral CI users. The results also indicated that pitch mismatches persist even with extended bilateral CI experience. Such mismatches may reduce the benefits patients receive from bilateral CIs.

Background - The use of bridge therapy with low-molecular-weight heparin during warfarin interruption for elective surgical and invasive diagnostic procedures leads to excess bleeding compared to interrupting warfarin alone. Other predictors of periprocedural bleeding during warfarin interruption are not well described. Aims - The purpose of this analysis was to identify predictors of major bleeding during and within 37 days after warfarin interruption for invasive procedures. Methods - BRIDGE was a double-blind, placebo controlled trial that randomized patients with atrial fibrillation requiring warfarin interruption to either bridge therapy with dalteparin 100IU/kg every 12 hours or matching placebo injections. Bleeding and thromboembolic outcomes were collected up to 37 days after the procedure. Multiple logistic regression models were used for baseline prediction of major bleeding. Time-dependent hazard models were used to add the effect of concomitant variables such as aspirin use and elevated INR values. Results - Nine hundred and fifty patients were assigned to placebo and 934 to dalteparin. Aspirin use at baseline was identified in 34.7% of the cohort (n=653) of which 60.5% (n=395) continued uninterrupted throughout the study period. The majority of procedures (89.4%) were considered low bleeding risk based on the planned surgical procedure. The median time to major bleeding was 7.0 days after surgery (interquartile range 4.0 to 18.0). Dalteparin administration was a baseline predictor of major bleeding (Odds Ratio (OR) = 2.5; 95% Confidence Interval (CI) 1.2-5.0, p=0.01), as was history of heart failure (OR=1.9; 95% CI 1.0-3.5, p=0.04) and major surgery (versus minor procedure) (OR=2.5; 95% CI 1.2-5.3, p=0.02). The current use of aspirin (OR=4.6; 95% CI 1.6-13.0, p=0.007) was significant as a time-dependent predictor of major bleeding. The presence of an elevated INR value (above 3.0) was not found to be significant when aspirin use was included in the model. Several factors known to contribute to bleeding risk during chronic anticoagulation were not found to predict bleeding around invasive procedures including age, history of hypertension, and history of gastrointestinal bleeding. The effect of history of diabetes, history of vascular disease, and gender were also evaluated but likewise these factors were not found to be significant predictors of bleeding. Conclusions - Major surgery, a history of heart failure and aspirin increase the risk of major bleeding during surgical and invasive diagnostic procedures requiring warfarin interruption. The risk and benefit of aspirin use during invasive procedures should be carefully assessed to minimize bleeding risk in this setting

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that, in a small proportion of people, precedes the development of oral cancer. Most leukoplakias are asymptomatic; therefore, the primary objective of treatment should be to prevent onset of cancer. This review updates our previous review, published in 2006. OBJECTIVES: To assess the effectiveness, safety and acceptability of treatments for leukoplakia in preventing oral cancer. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 16 May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 4), MEDLINE Ovid (1946 to 16 May 2016), Embase Ovid (1980 to 16 May 2016) and CancerLit via PubMed (1950 to 16 May 2016). We searched the metaRegister of Controlled Trials (to 10 February 2015), ClinicalTrials.gov (to 16 May 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (to 16 May 2016). We placed no restrictions on the language or date of publication when searching electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with a diagnosis of oral leukoplakia and compared any treatment versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: We collected data using a data extraction form. Oral cancer development, demonstrated by histopathological examination, was our primary outcome. Secondary outcomes were clinical resolution of the lesion, improvement of histological features and adverse events. We contacted trial authors for further details when information was unclear. When valid and relevant data were available, we conducted a meta-analysis of the data using a fixed-effect model when we identified fewer than four studies with no heterogeneity. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). We assessed risk of bias in studies by using the Cochrane tool. We assessed the overall quality of the evidence by using standardised criteria (Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE)). MAIN RESULTS: We included 14 studies (909 participants) in this review. Surgical interventions, including laser therapy and cryotherapy, have never been studied by means of an RCT that included a no treatment or placebo arm. The included trials tested a range of medical and complementary treatments, in particular, vitamin A and retinoids (four studies); beta carotene or carotenoids (three studies); non-steroidal anti-inflammatory drugs (NSAIDs), specifically ketorolac and celecoxib (two studies); herbal extracts (four studies), including tea components, a Chinese herbal mixture and freeze-dried black raspberry gel; bleomycin (one study); and Bowman-Birk inhibitor (one study).We judged one study to be at low risk of bias, seven at unclear risk and six at high risk. In general, we judged the overall quality of the evidence to be low or very low, so findings are uncertain and further research is needed.Five studies recorded cancer incidence, only three of which provided useable data. None of the studies provided evidence that active treatment reduced the risk of oral cancer more than placebo: systemic vitamin A (RR 0.11, 95% CI 0.01 to 2.05; 85 participants, one study); systemic beta carotene (RR 0.71, 95% CI 0.24 to 2.09; 132 participants, two studies); and topical bleomycin (RR 3.00, 95% CI 0.32 to 27.83; 20 participants, one study). Follow-up ranged between two and seven years.Some individual studies suggested effectiveness of some proposed treatments, namely, systemic vitamin A, beta carotene and lycopene, for achieving clinical resolution of lesions more often than placebo. Similarly, single studies found that systemic retinoic acid and lycopene may provide some benefit in terms of improvement in histological features. Some studies also reported a high rate of relapse.Side effects of varying severity were often described; however, it seems likely that interventions were well accepted by participants because drop-out rates were similar between treatment and control groups. AUTHORS' CONCLUSIONS: Surgical treatment for oral leukoplakia has not been assessed in an RCT that included a no treatment or placebo comparison. Nor has cessation of risk factors such as smoking been assessed. The available evidence on medical and complementary interventions for treating people with leukoplakia is very limited. We do not currently have evidence of a treatment that is effective for preventing the development of oral cancer. Treatments such as vitamin A and beta carotene may be effective in healing oral lesions, but relapses and adverse effects are common. Larger trials of longer duration are required to properly evaluate the effects of leukoplakia treatments on the risk of developing oral cancer. High-quality research is particularly needed to assess surgical treatment and to assess the effects of risk factor cessation in people with leukoplakia.

BACKGROUND: Commonly occurring in the head and neck, paragangliomas are typically benign, highly vascular neoplasms embryologically originating from the extra-adrenal paraganglia of the neural crest. Frequently, these tumors are associated with the vagus or tympanic plexus nerve or the carotid artery, or jugular bulb. Their clinical presentation can vary across a wide spectrum of signs and symptoms. METHODS: We reviewed and compared standard treatment approaches for paragangliomas of the head and neck. RESULTS: In general, surgery is the first-line choice of therapy for carotid body tumors, whereas radiotherapy is the first-line option for jugular and vagal paragangliomas. CONCLUSIONS: Because of the complexity of clinical scenarios and treatment options for paragangliomas, a multidisciplinary algorithmic approach should be used for treating paragangliomas. The approach should emphasize single-modality treatment that yields excellent rates of tumor control, low rates of severe, iatrogenic morbidity, and the preservation of long-term function in this patient population.

Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. OBJECTIVE: To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. MATERIALS AND METHODS: Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new 'cytology-on-a-chip' approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. RESULTS: Binary "low-risk"/"high-risk" models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity+specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. CONCLUSIONS: This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum.