Can Preoperative CT Scans Be Used to Predict Facial Nerve Stimulation Following CI?

OBJECTIVES: 1) To determine the ability of preoperative computed tomography (CT) to predict facial nerve stimulation (FNS) after cochlear implantation (CI). 2) To recognize the limitations of CT in predicting FNS. STUDY DESIGN: Patient control study. SETTING: Tertiary care academic medical center. SUBJECTS: Adult patients with CI from 2003 to 2015. METHODS: Patients with severe FNS (n = 4) were compared with randomly selected CI patients (n = 28). Three blinded reviewers evaluated preoperative temporal bone CT scans to measure the distance from the labyrinthine segment of the facial nerve to the basal turn of the cochlea and attempted to predict whether or not the subject had FNS after CI. RESULTS: In total, 32 CT scans were evaluated representing 49 ears that underwent CI.The distances (mm) measured from the labyrinthine segment of the facial nerve to the basal turn of the cochlea in both the axial (0.3 ±â€Š0.3 versus 0.6 ±â€Š0.3) and coronal (0.4 ±â€Š0.2 versus 0.6 ±â€Š0.2) orientation were significantly different between the two groups (p = 0.0001 and p = 0.0034) respectively. The intraclass correlation coefficient demonstrated good (K > 0.7) reviewer correlation in both the reviewers' measurements and predictions. The sensitivity, specificity, positive predictive value, and negative predictive value for preoperative CT scans to predict FNS were 38.5, 85.1, 19.2, and 93.8% respectively. The reviewers were 23% accurate in predicting FNS. CONCLUSION: Based on a blinded retrospective patient-control study, CT scan measurements show a significantly reduced distance between the labyrinthine facial nerve and the basal turn of the cochlea in patients with FNS. However, it is difficult to predict who will have FNS based on these measurements.

Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.

Age-related hearing loss (presbycusis) is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old) and aged (2-2.5 year-old) mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+) cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells) in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+) marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+) cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+) cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+) cells may also be associated with a decline in the repair capabilities of non-sensory cells in the aged ear.

Effects of orexin 2 receptor activation on apnea in the C57BL/6J mouse.

BACKGROUND: The hypothesis was that an orexin 2 receptor (OX2R) agonist would prevent sleep-related disordered breathing. METHODS: In C57BL/6J (B6) mice, body plethysmography was performed with and without EEG monitoring of state (wakefulness, NREM and REM sleep). Outcome was apnea rate/h during sleep-wake states at baseline and with an intracerebroventricular administration of vehicle, 4 nMol of agonist OB(DL), and 4 nMol of an antagonist, TCS OX2 29. RESULTS: A significant reduction (p=0.035, f=2.99) in apneas/hour occurred, especially with the agonist. Expressed as a function of the change from baseline, there was a significant difference among groups in Wake (p=0.03, f=3.8), NREM (p=0.003, f=6.98) and REM (p=0.03, f=3.92) with the agonist reducing the rate of apneas during sleep from 29.7±4.7 (M±SEM) to 7.3±2.4 during sleep (p=0.001). There was also a reduction in apneas during wakefulness. Administration of the antagonist did not increase event rate over baseline levels. CONCLUSIONS: The B6 mouse is a preclinical model of wake-and sleep-disordered breathing, and the orexin receptor agonist at a dose of 4 nMol given intracerebroventricularly will reduce events in sleep and also wakefulness.

Identification of novel mouse genes conferring posthypoxic pauses.

Although central to the susceptibility of adult diseases characterized by abnormal rhythmogenesis, characterizing the genes involved is a challenge. We took advantage of the C57BL/6J (B6) trait of hypoxia-induced periodic breathing and its absence in the C57BL/6J-Chr 1(A/J)/NaJ chromosome substitution strain to test the feasibility of gene discovery for this abnormality. Beginning with a genetic and phenotypic analysis of an intercross study between these strains, we discovered three quantitative trait loci (QTLs) on mouse chromosome 1, with phenotypic effects. Fine-mapping reduced the genomic intervals and gene content, and the introgression of one QTL region back onto the C57BL/6J-Chr 1(A/J)/NaJ restored the trait. mRNA expression of non-synonymous genes in the introgressed region in the medulla and pons found evidence for differential expression of three genes, the highest of which was apolipoprotein A2, a lipase regulator; the apo a2 peptide fragment (THEQLTPLVR), highly expressed in the liver, was expressed in low amounts in the medulla but did not correlate with trait expression. This work directly demonstrates the impact of elements on mouse chromosome 1 in respiratory rhythmogenesis.

Late dysphagia after radiotherapy-based treatment of head and neck cancer.

BACKGROUND: Changing trends in head and neck cancer (HNC) merit an understanding of the late effects of therapy, but few studies examine dysphagia beyond 2 years of treatment. METHODS: A case series was examined to describe the pathophysiology and outcomes in dysphagic HNC survivors referred for modified barium swallow (MBS) studies ≥ 5 years after definitive radiotherapy or chemoradiotherapy (January 2001 through May 2011). Functional measures included the penetration-aspiration scale (PAS), performance status scale-head and neck (PSS-HN), National Institutes of Health Swallowing Safety Scale (NIH-SSS), and MBS impairment profile (MBSImp). RESULTS: Twenty-nine patients previously treated with radiotherapy (38%) or chemoradiotherapy (62%) were included (median years posttreatment, 9; range, 5-19). The majority (86%) had oropharyngeal cancer; 52% were never-smokers. Seventy-five percent had T2 or T3 tumors; 52% were N+. The median age at diagnosis was 55 (range, 38-72). Abnormal late examination findings included: dysarthria/dysphonia (76%), cranial neuropathy (48%), trismus (38%), and radionecrosis (10%). MBS studies confirmed pharyngeal residue and aspiration in all dysphagic cases owing to physiologic impairment (median PAS, 8; median NIH-SSS, 10; median MBSImp, 18), whereas stricture was confirmed endoscopically in 7 (24%). Twenty-five (86%) developed pneumonia, half requiring hospitalization. Swallow postures/strategies helped 69% of cases, but no patient achieved durable improvement across functional measures at last follow-up. Ultimately, 19 (66%) were gastrostomy-dependent. CONCLUSIONS: Although functional organ preservation is commonly achieved, severe dysphagia represents a challenging late effect that may develop or progress years after radiation-based therapy for HNC. These data suggest that novel approaches are needed to minimize and better address this complication that is commonly refractory to many standard dysphagia therapies.

Transoral robotic-assisted thyroidectomy with central neck dissection: preclinical cadaver feasibility study and proposed surgical technique.

UNLABELLED: Recently, a transoral robotic-assisted technique to access the thyroid gland has been introduced. Despite the advantages this approach may have over other minimally invasive and robotic-assisted techniques, we found that the placement of the camera through the floor of mouth led to restricted freedom of movement. We describe our modification to this technique to overcome this problem. In a study using two fresh human cadavers, the camera port of the da Vinci robot was placed in the midline oral vestibule instead of the floor of the mouth. A transoral thyroidectomy and central neck dissection was successfully performed. Our modification led to an unfettered view of the central neck and allowed for a total thyroidectomy and central neck dissection. Our modification of transoral robotic-assisted thyroidectomy provides superior access to the central compartment of the neck over other robotic-assisted thyroidectomy techniques. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11701-011-0287-2) contains supplementary material, which is available to authorized users.

Effects of hydrogen sulfide synthesis inhibitors on posthypoxic ventilatory behavior in the C57BL/6J mouse.

BACKGROUND: H(2)S synthesis inhibitors (HSSI) have been shown to impact respiratory control. For instance, the HSSI hydroxylamine (HA) decreases the respiratory discharge rate from isolated medullary sections, and HA in addition to other HSSIs propargylglycine and amino-oxyacetic acid (AOAA) have been found to reduce hypoxic responsiveness. OBJECTIVES: The aim of this study was to determine if administration of HSSIs could improve respiratory stability in an intact organism prone to recurrent central apneas. METHODS: Saline and HSSI compounds were administered to C57BL/6J mice (n = 24), a strain predisposed to recurrent central apneas, prior to measurement of hypoxic and posthypoxic ventilatory behavior. RESULTS: Administration of HA and AOAA resulted in a significantly smaller percentage of animals expressing one or more apneas during reoxygenation compared to saline control, and animals given AOAA demonstrated a smaller coefficient of variation for frequency during reoxygenation, a marker suggesting greater respiratory stability. This occurred despite varying effects of the three HSSI compounds on hypoxic ventilatory response. CONCLUSIONS: Instability and pause expression are improved by targeting H(2)S synthesis, an effect not predicted by effects on hypoxic responsiveness.

Retropharyngeal lymphadenectomy with transoral robotic surgery for papillary thyroid cancer.

Retropharyngeal metastasis of papillary thyroid carcinoma is a rare but well recognized phenomenon. Traditional open surgical approaches to nodal metastasis located in the retropharyngeal space are particularly morbid considering the relatively indolent nature of some thyroid cancers. Minimally invasive surgical approaches offer a useful alternative that is both low in morbidity and high in levels of patient acceptance. To assess feasibility and safety, we report a case series of robotic lymphadenectomy in two patients with thyroid cancer metastatic to the retropharyngeal space. Two patients, ages 66 and 73, with unilateral recurrent papillary carcinoma of the retropharyngeal lymph nodes had previously undergone thyroidectomy, neck dissection, and radioactive iodine ablation prior to retropharyngeal resection. Retropharyngeal lymphadenectomy via transoral robotic surgery was performed for both patients: for the first, the oropharyngeal wound was left to heal by secondary intention, while for the other patient, simple pharyngeal flap closure was performed. Retropharyngeal lymph node dissections were successfully carried out using a transoral robotic retropharyngotomy with the da Vinci surgical robotic system. Both patients tolerated the procedure well. One patient did developed temporary dysphagia which resolved with conservative measures, not requiring a feeding tube. We report the first two cases of transoral robot-assisted resection of thyroid cancer metastatic to the retropharyngeal lymph nodes. The technique is feasible, minimally invasive, and appears to be as safe as conventional surgical methods in achieving the goals of management of regionally metastatic disease.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression.

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 microM epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.

Circadian rhythms in myocardial metabolism and contractile function: influence of workload and oleate.

Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from male Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM, and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H(2)O afterload), hearts were challenged with increased workload (140 cm H(2)O afterload plus 1 microM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase. Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability.

How managed care has affected mental health case management activities, caseloads, and tenure.

The purpose of this study was to identify changes in case management within public sector mental health, following the implementation of managed care. Case managers in the State of Oregon completed surveys in 1992 and 2000 regarding aspects of case management. Results showed that current case managers are more experienced and expect longer tenure than previously. Caseload sizes have increased. Meanwhile, case managers' activities and functions have not changed across time periods. The results suggest that mental health personnel have changed in the past decade, though the practice of case management has remained largely the same.