1) To determine the relationship of electrocochleography (ECochG) responses measured on the promontory with responses measured at the round window (RW) and various intracochlear sites. 2) To evaluate if promontory ECochG responses correlate with postoperative speech-perception performance using the cochlear implant (CI).Prospective cohort study.Tertiary referral center.Ninety-six adult CI recipients with no cochlear malformations or previous otologic surgery.Acoustically evoked ECochG responses were measured intraoperatively at both extracochlear and intracochlear locations. ECochG total response (ECochG-TR), a measure of residual cochlear function, was calculated by summing the fast Fourier transformation amplitudes in response to 250-Hz to 2-kHz acoustic stimuli. Speech-perception performance was measured at 3 months.There were strong linear correlations for promontory ECochG-TR with the ECochG-TRs measured at the RW ( r = 0.95), just inside scala tympani ( r = 0.91), and after full insertion ( r = 0.83). For an individual subject, the morphology of the ECochG response was similar in character across all positions; however, the response amplitude increased from promontory to RW (~1.6-fold) to just inside scala tympani (~2.6-fold), with the largest response at full insertion (~13.1-fold). Promontory ECochG-TR independently explained 51.8% of the variability ( r2 ) in consonant-nucleus-consonant at 3 months.Promontory ECochG recordings are strongly correlated with responses previously recorded at extracochlear and intracochlear sites and explain a substantial portion of the variability in CI performance. These findings are a critical step in supporting translation of transtympanic ECochG into the clinic preoperatively to help predict postoperative CI performance.
Cisplatin is an effective anticancer agent, but also causes permanent hearing loss by damaging hair cells-the sensory receptors essential for hearing. There is an urgent clinical need to protect cochlear hair cells in patients undergoing cisplatin chemotherapy. The zebrafish lateral line organ contains hair cells and has been frequently used in studies to screen for otoprotective compounds. However, these studies have employed a wide range of cisplatin dosages and exposure times. We therefore performed a comprehensive evaluation of cisplatin ototoxicity in the zebrafish lateral line with the goal of producing a standardized, clinically relevant protocol for future studies. To define the dose- and time-response patterns of cisplatin-induced hair-cell death, we treated 6-day-old larvae for 2 h in 50 µM-1 mM cisplatin and allowed them to recover. We observed delayed hair cell death, which peaked at 4-8 h post-exposure. Cisplatin also activated a robust inflammatory response, as determined by macrophage recruitment and phagocytosis of hair cells. However, selective depletion of macrophages did not affect hair cell loss. We also examined the effect of cisplatin treatment on fish behavior and found that cisplatin-induced lateral line injury measurably impaired rheotaxis. Finally, we examined the function of remaining hair cells that appeared resistant to cisplatin treatment. We observed significantly reduced uptake of the cationic dye FM1-43 in these cells relative to untreated controls, indicating that surviving hair cells may be functionally impaired. Cumulatively, these results indicate that relatively brief exposures to cisplatin can produce hair cell damage and delayed hair cell death. Our observations provide guidance on standardizing methods for the use of the zebrafish model in studies of cisplatin ototoxicity.
Introduction: Wide-angle endoscopy is an emerging technique that aims to improve lesion detection through better visualization with a trend toward improved adenoma detection rate (ADR). We sought to evaluate the procedural characteristics of the Full-Spectrum Endoscopy (Fuse®) system. Methods: This single-center retrospective cohort study reviews 974 colonoscopies performed since January 2015. The type of colonoscope used was randomly determined for a given endoscopy block on the day of the procedure by the nursing staff. Data were collected on age, gender, indication for colonoscopy, and bowel preparation quality. Insertion and withdrawal time (WT), as well as sedative doses (midazolam, fentanyl, diphenhydramine), and reversal agent use (naloxone, flumazenil) were recorded. The primary outcomes of insertion time and sedative requirements were compared between the Fuse® and conventional (Olympus 190) colonoscope exams.Table: Table. Colonoscopy Descriptive AnalysisTable: Table. Standard Colonoscopy vs Fuse Colonoscopy Baseline Data Comparison:Results: Of the total 974 patients, 770 underwent standard colonoscopy while 204 underwent Fuse® colonoscopy. Mean age was 59.4 years and majority were female (56.9%). Colorectal cancer screening or surveillance was the most common indication (50.9%), followed by gastrointestinal bleeding (19.4%). Cecal intubation rate was 98.4% while mean WT was 13.5 minutes. There were no significant differences in demographics, preparation quality, or cecal intubation rate between both groups. Adenoma Detection Rate (ADR), calculated on a subset of patients who underwent screening colonoscopy with two endoscopists, was higher with Fuse® colonoscopy compared to standard colonoscopy however this did not meet statistical significance (32.5% vs 25.1%, p=0.146). There was no difference in mean WT (Fuse® 13.9 min vs standard 13.4 min, P=0.36) however mean insertion time was longer for Fuse® colonoscopies (12.3 mins vs 9.2 mins, P= < 0.01). Adjunctive sedative use (diphenhydramine) was more often required with Fuse® (33.5%) than standard colonoscopy (27.3%, p = 0.008). The mean fentanyl dose administered was higher in the Fuse® group (111.7 mcg vs 101.4 mcg, P= < 0.01). No difference existed between midazolam dose or the use of reversal agents. Conclusion: Insertion time was significantly longer for Fuse® cases, with higher sedative requirements. It is unclear if the increased insertion time was related to patient's discomfort and increased sedative requirements. Further prospective studies are needed to evaluate the technical performance of the Fuse® colonoscope.
This study was designed to assess the feasibility and safety of enoxaparin in combination with glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary intervention (PCI) as part of an early invasive strategy in patients presenting with acute coronary syndromes (ACS).Trials in patients with ACS have evaluated the utility of enoxaparin, adjuvant GP IIb/IIIa inhibitors with PCI, and an early invasive approach. Information about the combination of all three of these approaches, however, is limited.Forty-nine patients with ACS underwent cardiac catheterization, of whom 23 underwent PCI with enoxaparin and GP IIb/IIIa inhibitors.The primary endpoint of the study, a composite of death, myocardial infarction or urgent revascularization at 30 days, occurred in 8% of patients undergoing PCI. There were no deaths. One patient received a blood transfusion. No other adverse events occurred. These event rates were comparable to those from the pooled EPILOG/EPISTENT database, in which intravenous unfractionated heparin was used in conjunction with GP IIb/IIIa receptor blockade. The mean anti-Xa level in patients undergoing PCI was 0.74 0.48 U/ml. The majority of patients who underwent PCI within eight hours of their last dose of enoxaparin had therapeutic anti-Xa levels.In patients with ACS, enoxaparin in combination with GP IIb/IIIa inhibitors and an early invasive approach resulted in comparable clinical complication and bleeding rates versus historical references utilizing unfractionated heparin.
Uveal melanoma is the most common primary ocular malignancy, although it is rare in children, and patients presenting with metastatic disease have a median survival of only 2 to 5 months. The tumor is generally unresponsive to systemic chemotherapy, but immunotherapy may be effective in selected patients. This report describes an 8-year-old girl with metastatic uveal melanoma treated with high-dose, bolus interleukin-2 (IL-2) and the antiangiogenic agent thalidomide. She tolerated treatment well and initially responded with stable disease in the liver and pancreas for 23 months. New pulmonary metastases developed and she was re-treated with high-dose IL-2, resulting in regression of her liver lesions and stable pulmonary disease for more than 18 months. These results suggest that IL-2 at high doses, and in combination with thalidomide, may be useful for uveal melanoma with tolerable side effects in children. Further study of this combination in children with immune-responsive tumors is warranted.
Objective To evaluate whether electrocochleography (ECochG)-guided pull-back of the perimodiolar electrode improves perimodiolar proximity, hearing preservation (HP), and cochlear implant performance. Study Design Prospective cohort study Setting Tertiary referral center. Patients 77 adult CI recipients with residual acoustic hearing (low-frequency pure-tone average of 125, 250, 500 Hz; LFPTA ≤80 dB HL) Intervention Unilateral implantation, comparing conventional insertion (N = 31) with ECochG-guided electrode pull-back (N = 46). The guided method uses active ECochG from the apical electrode during adjustment and post-insertion electrode sweep to identify “tonotopic response” (defined as maximum response for 250 Hz at most apical electrode on electrode sweep). Main Outcome Measures Perimodiolar proximity (wrapping factor on postoperative CT); speech-perception testing (CNC, AzBio in noise +10 dB SNR); and HP at 3 and 6 months post-activation (defined as LFPTA ≤80 dB HL). Results Of the subjects undergoing ECochG-guided insertion, 36 required pull-back based on lack of tonotopic responses, whereas the remaining 10 exhibited “optimal responses” post-insertion, needing no adjustment. Improved perimodiolar proximity was achieved with the ECochG-guided method (mean wrapping factor difference, 6.4; 95% CI, 3.0–9.9). The LFPTA shift was smaller using ECochG-guided pull-back when compared with conventional insertion by 17.0 dB HL (95% CI, 8.3–25.7) and 14.8 dB HL (95% CI, 6.5–23.2) at 3 and 6 months, respectively. Forty percent achieved HP using ECochG-guided pull-back versus 27.5% without. There was no difference in CNC scores among both cohorts, but AzBio in noise scores at 6 months was improved in the ECochG-guided pull-back cohort (mean difference, 19.1%; 95% CI, 5.8–32.4). Conclusions ECochG-guided pull-back increased perimodiolar proximity and HP rates. Although there was no difference in speech perception performance in quiet, a significant improvement was noted in noisy conditions, potentially attributable to HP and the utilization of hybrid stimulation.
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