Objectives/Hypothesis:Previous feasibility studies have shown that electrical stimulation of the hypoglossal nerve can improve obstructive sleep apnea (OSA). The current study examined the safety and preliminary effectiveness of a second generation device, the Upper Airway Stimulation (UAS) system, and identified baseline predictors for therapy success.Study Design:Two consecutive open prospective studies.Methods:UAS systems were implanted in patients with moderate to severe OSA who failed or were intolerant of continuous positive airway pressure (CPAP). The study was conducted in 2 parts. In part 1, patients were enrolled with broad selection criteria. Apnea hypopnea index (AHI) was collected using laboratory‐based polysomnography at preimplant and postimplant visits. Epworth Sleepiness Scale (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also collected. In part 2, patients were enrolled using selection criteria derived from the experience in part 1.Results:In part 1, 20 of 22 enrolled patients (two exited the study) were examined for factors predictive of therapy response. Responders had both a body mass index ≤32 and AHI ≤50 (P < .05) and did not have complete concentric palatal collapse. Part 2 patients (n = 8) were selected using responder criteria and showed an improvement on AHI from baseline, from 38.9 ± 9.8 to 10.0 ± 11.0 (P < .01) at 6 months postimplant. Both ESS and FOSQ improved significantly in part 1 and 2 subjects.Conclusions:The current study has demonstrated that therapy with upper airway stimulation is safe and efficacious in a select group of patients with moderate to severe OSA who cannot or will not use CPAP as primary treatment. Laryngoscope, 2012

Contraction of the genioglossus (GG) has been shown to improve upper airway patency. In the present study, we evaluated responses in upper airway pressure-flow relationships during sleep to electrical stimulation (ES) of the GG in patients with obstructive sleep apnea. Five patients with chronically implanted hypoglossal nerve (HG) electrodes and nine patients with fine-wire electrodes inserted into the GG were studied. Airflow was measured at multiple levels of nasal pressure, and upper airway collapsibility was defined by the nasal pressure below which airflow ceased ["critical" pressure (Pcrit)]. ES shifted the pressure-flow relationships toward higher flow levels in all patients over the entire range of nasal pressure applied. Pcrit decreased similarly during both HG-ES and GG-ES (deltaPcrit was 3.98 +/- 2.31 and 3.18 +/- 1.70 cmH2O, respectively) without a significant change in upstream resistance. The site of collapse (velo- vs. oropharynx) did not influence the response to GG-ES. Moreover, ES-induced reductions in the apnea-hypopnea index of the HG-ES patients were associated with substantial decreases in Pcrit. Our findings imply that responses in apnea severity to HG-ES can be predicted by characterizing the patient's baseline pressure-flow relationships and response to GG-ES.

The purpose of the present study was to quantify the mechanical effect of genioglossus stimulation on flow mechanics and pharyngeal cross-sectional area in patients with obstructive sleep apnoea, and to identify variables that determine the magnitude of the respiratory effect of tongue protrusion.The pressure/flow and pressure/cross-sectional area relationships of the velo-and oropharynx were assessed in spontaneously breathing propofol-anaesthetised subjects before and during genioglossus stimulation.Genioglossus contraction decreased the critical pressure significantly from 1.2¡3.3 to -0.7¡3.8 cmH 2 O, with individual decreases ranging -0.6-5.9 cmH 2 O. Pharyngeal compliance was not affected by genioglossus contraction. The pharyngeal response to genioglossus stimulation was related to the magnitude of advancement of the posterior side of the tongue, but not to the severity of sleep apnoea, critical pressure, compliance or the shape and other characteristics of the velopharynx.Genioglossus contraction enlarges both the velo-and the oropharynx and lowers the critical pressure without affecting pharyngeal stiffness. The response to genioglossus stimulation depends upon the magnitude of tongue protrusion achieved rather than on inherent characteristics of the patient and their airway.

BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Serum levels of TNF correlate positively with the severity of HE in patients with chronic liver failure.

The results of this study demonstrate a significant relationship between TNF and ammonia in patients with chronic liver failure and HE, and so strengthen the suggestion that TNF could be strongly involved in the pathogenesis of HE in these patients. Hence, we suggest a new theory in the pathogenesis of HE, the "TNF theory".

This study was undertaken in an attempt to characterize the acoustic properties of snoring sounds in the time and frequency domains, and to correlate between these properties and the mechanical events underlying their production. Three experimental set-ups were used: 1) Dog model--six mongrel dogs, in which partial upper airway obstruction was created by an implanted supraglottic balloon. Flow, supraglottic pressure, and snoring sounds were recorded during different degrees of obstruction. Fifteen to 20 snores from each dog (total 100 snores) were analysed. 2) Simulated human snores--Six simulated snores from each of four subjects were recorded in two locations (trachea and ambient) with simultaneous airflow, and their correlations examined. 3) Snoring patients--snores were recorded with an ambient microphone from nine subjects with "heavy" snoring and no obstructive sleep apnoea (OSA). Forty to 50 snores from each subject were analysed (total of 400 snores). The snoring sound was analysed in the time (time-expanded waveform) and frequency (power spectrum) domains. After analysing these snores, we were able to identify two dominant patterns which are distinctly different from each other: the "simple-waveform" and the "complex-waveform". The complex-waveform snore is characterized by repetitive, equally-spaced, train of sound structures, starting with a large deflection followed by a decaying amplitude wave. In the frequency domain, it is characterized by multiple, equally-spaced peaks of power (comb-like spectrum). Simple-waveform snores have a quasi-sinusoidal waveform, with a range of variants, and almost no secondary internal oscillations. Their power spectrum contains only 1-3 peaks, of which the first is the most prominent. We developed a mathematical representation of these waveforms, which is presented along with its implications. The complex-waveform snores result from colliding of the airway walls and represent actual brief airway closure. Simple-waveform snores are of higher frequency and probably result from oscillation around a neutral position without actual closure of the lumen.

The present study evaluated the effect of coactivation of tongue protrusors and retractors on pharyngeal patency in patients with obstructive sleep apnea. The effect of genioglossus (GG), hyoglossus (HG), and coactivation of both on nasal pressure (Pn):flow relationships was evaluated in a sleep study (SlS, n = 7) and during a propofol anesthesia study (AnS, n = 7). GG was stimulated with sublingual surface electrodes in SlS and with intramuscular electrodes in AnS, while HG was stimulated with surface electrodes in both groups. In the AnS, the cross-sectional area (CSA):Pn relationships was measured with a pharyngoscope to estimate velopharyngeal compliance . In the SlS, surface stimulation of GG had no effect on the critical pressure (Pcrit), HG increased Pcrit from 2.8 +/- 1.7 to 3.7 +/- 1.6 cmH(2)O, but coactivation lowered Pcrit to 0.2 +/- 1.9 cmH(2)O (P < 0.01 for both). In the AnS, intramuscular stimulation of GG lowered Pcrit from 2.6 +/- 1.3 to 1.0 +/- 2.8 cmH(2)O, HG increased Pcrit to 6.2 +/- 2.5 cmH(2)O (P < 0.01), and coactivation had a similar effect to that of GG (Pcrit = 1.2 +/- 2.4 cmH(2)O, P < 0.05). None of the interventions affected significantly velopharyngeal compliance. We conclude that the beneficial effect of coactivation depends on the pattern of GG fiber recruitment: although surface stimulation of GG failed to protrude the tongue, it prevented the occlusive effect of the retractor, thereby improving pharyngeal patency during coactivation. Stimulation of deeper GG fibers with intramuscular electrodes enlarged the pharynx, and coactivation had no additive effect.