Inflammatory heterogeneity in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a mechanistically distinct subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Although frequently associated with type 2 inflammation, literature characterizing the milieu of inflammatory cytokines and lipid mediators in AERD has been conflicting. OBJECTIVE: We sought to identify differences in the upper airway inflammatory signature between CRSwNP and AERD and determine whether endotypic subtypes of AERD may exist. METHODS: Levels of 7 cytokines representative of type 1, type 2, and type 3 inflammation, and 21 lipid mediators were measured in nasal mucus from 109 patients with CRSwNP, 30 patients with AERD, and 64 non-CRS controls. Differences in inflammatory mediators were identified between groups, and patterns of inflammation among patients with AERD were determined by hierarchical cluster analysis. RESULTS: AERD could be distinguished from CRSwNP by profound elevations in IL-5, IL-6, IL-13, and IFN-γ; however, significant heterogeneity existed between patients. Hierarchical cluster analysis identified 3 inflammatory subendotypes of AERD characterized by (1) low inflammatory burden, (2) high type 2 cytokines, and (3) comparatively low type 2 cytokines and high levels of type 1 and type 3 cytokines. Several lipid mediators were associated with asthma and sinonasal disease severity; however, lipid mediators showed less variability than cytokines. CONCLUSIONS: AERD is associated with elevations in type 2 cytokines (IL-5 and IL-13) and the type 1 cytokine, IFN-γ. Among patients with AERD, the inflammatory signature is heterogeneous, supporting subendotypes of the disease. Variability in AERD immune signatures should be further clarified because this may predict clinical response to biologic medications that target type 2 inflammation.

Hair cell and neural contributions to the cochlear summating potential.

The cochlear summating potential (SP) to a tone is a baseline shift that persists for the duration of the burst. It is often considered the most enigmatic of cochlear potentials because its magnitude and polarity vary across frequency and level and its origins are uncertain. In this study, we used pharmacology to isolate sources of the SP originating from the gerbil cochlea. Animals either had the full complement of outer and inner hair cells (OHCs and IHCs) and an intact auditory nerve or had systemic treatment with furosemide and kanamycin (FK) to remove the outer hair cells. Responses to tone bursts were recorded from the round window before and after the neurotoxin kainic acid (KA) was applied. IHC responses were then isolated from the post-KA responses in FK animals, neural responses were isolated from the subtraction of post-KA from pre-KA responses in NH animals, and OHC responses were isolated by subtraction of post-KA responses in FK animals from post-KA responses in normal hearing (NH) animals. All three sources contributed to the SP; OHCs with a negative polarity and IHCs and the auditory nerve with positive polarity. Thus the recorded SP in NH animals is a sum of contributions from different sources, contributing to the variety of magnitudes and polarities seen across frequency and intensity. When this information was applied to observations of the SP recorded from the round window in human cochlear implant subjects, a strong neural contribution to the SP was confirmed in humans as well as gerbils. NEW & NOTEWORTHY Of the various potentials produced by the cochlea, the summating potential (SP) is typically described as the most enigmatic. Using combinations of ototoxins and neurotoxins, we show contributions to the SP from the auditory nerve and from inner and outer hair cells, which differ in polarity and vary in size across frequency and level. This complexity of sources helps to explain the enigmatic nature of the SP.

Objective Pharyngeal Phenotyping in Obstructive Sleep Apnea With High-Resolution Manometry.

OBJECTIVE: Drug-induced sleep endoscopy (DISE) is a commonly used diagnostic tool for surgical procedural selection in obstructive sleep apnea (OSA), but it is expensive, subjective, and requires sedation. Here we present an initial investigation of high-resolution pharyngeal manometry (HRM) for upper airway phenotyping in OSA, developing a software system that reliably predicts pharyngeal sites of collapse based solely on manometric recordings. STUDY DESIGN: Prospective cross-sectional study. SETTING: An academic sleep medicine and surgery practice. METHODS: Forty participants underwent simultaneous HRM and DISE. A machine learning algorithm was constructed to estimate pharyngeal level-specific severity of collapse, as determined by an expert DISE reviewer. The primary outcome metrics for each level were model accuracy and F1-score, which balances model precision against recall. RESULTS: During model training, the average F1-score across all categories was 0.86, with an average weighted accuracy of 0.91. Using a holdout test set of 9 participants, a K-nearest neighbor model trained on 31 participants attained an average F1-score of 0.96 and an average accuracy of 0.97. The F1-score for prediction of complete concentric palatal collapse was 0.86. CONCLUSION: Our findings suggest that HRM may enable objective and dynamic mapping of the pharynx, opening new pathways toward reliable and reproducible assessment of this complex anatomy in sleep.

Ansa cervicalis stimulation increases pharyngeal patency in patients with obstructive sleep apnea.

Hypoglossal nerve stimulation (HNS) is an alternative treatment option for obstructive sleep apnea (OSA) that reduces pharyngeal collapsibility, but HNS nonresponders often demonstrate continued retropalatal and lateral pharyngeal wall collapse. Recent evidence suggests that caudal pharyngeal traction with sternothyroid muscle contraction via ansa cervicalis stimulation (ACS) can also stabilize the pharynx, but the underlying mechanisms have not been elucidated. Our objective was to evaluate the effect of ACS on pharyngeal patency during expiration when the airway is most hypotonic. Eight participants with OSA underwent sustained ultrasound-guided fine-wire stimulation of the medial branch of the right hypoglossal nerve with and without transient stimulation of the branch of the ansa cervicalis nerve plexus innervating the right sternothyroid muscle during drug-induced sleep endoscopy. Airway cross-sectional area and expiratory airflow (V̇e) were measured from endoscopy video with ImageJ and pneumotachometry, respectively. ACS significantly increased retropalatal cross-sectional area (CSARP) to 211% [159-263] of unstimulated CSARP (P < 0.05). Adding ACS to HNS increased CSARP from baseline by 341% [244-439] (P < 0.05), a 180% [133-227] increase over isolated HNS (P < 0.05). ACS increased V̇e from baseline by 177% [138-217] P < 0.05). Adding ACS to HNS increased V̇e by 254% [207-301], reflecting decreases in pharyngeal collapsibility. Combining ACS with HNS increased retropalatal cross-sectional area and increased expiratory airflow, suggesting decreases in pharyngeal collapsibility. Our findings suggest that ACS exerts caudal traction on the upper airway through sternothyroid muscle contraction and that it may augment HNS efficacy in patients with OSA.NEW & NOTEWORTHY Ansa cervicalis stimulation (ACS) is a recently proposed neurostimulation mechanism for generating caudal pharyngeal traction that may benefit patients with obstructive sleep apnea. Here, we document endoscopic findings with ACS during drug-induced sleep endoscopy and additionally detail the effects of ACS on expiratory airflow, when the pharynx is known to be most hypotonic.

Long-term follow-up of trauma patients with permanent prophylactic vena cava filters.

BACKGROUND: Although permanent prophylactic Greenfield filters (PPGF) are effective, their use in young trauma patients who may eventually return to active lifestyles is controversial due to concerns about the safety of the devices over a lifetime. This descriptive study was undertaken to provide follow-up on the long-term safety and durability of PPGF. METHODS: All patients receiving a PPGF between April 1, 1992 and March 1, 2001 were sought for follow-up. Contacted patients were interviewed regarding known filter-related complications, venous thromboembolic events, and activity levels since the time of discharge from the hospital. Patients were also offered a physical examination focusing on venous thromboembolic sequelae, a plain film of the abdomen (KUB) to assess filter integrity and location, and an ultrasound to assess caval patency. As the original level of filter placement was usually not known, migration was defined as a filter above the first lumbar vertebra (L1). RESULTS: The eligible cohort consisted of 188 patients. Ninety were unable to be located (47.8%), one refused enrollment (0.5%), and 97 patients or next of kin agreed to be interviewed by phone (51.6%) of whom 69 returned for evaluation (36.7%). No filter-related complications were self-reported. KUBs were performed in 68 patients; one filter strut fracture was found (1.5%), whereas no filter migrations above L1 were noted. No instances of caval thrombosis were found in 55 ultrasounds. Two patients suffered interim pulmonary emboli (2.1%), one of which was fatal. Of 15 interim deaths, autopsy or death certificates were available for four patients, nine had their causes of death related by next of kin, and two were unknown. Although 95.4% of nonspinal cord injury patients reported at least some ability to ambulate, only 64.6% could do so ad libitum. Of those patients ambulating without limitation, 28.6% reported a complete inability to run any distance and another 23.8% could run less than one block. Follow-up for patients completing interviews was 105.3 months +/- 18.0 months, and for patients undergoing imaging was 104.6 months +/- 16.4 months. Interim deaths occurred at 48.2 months +/- 26.0 months. CONCLUSIONS: PPGF seem to be safe and effective at 105 months of follow-up; most patients report significant limitations in activity level at this same timeframe. PPGF should be the filter of choice for elderly patients in whom this time period can reasonably be expected to cover the patient's remaining life expectancy.

The Compound Action Potential in Subjects Receiving a Cochlear Implant.

HYPOTHESIS: The compound action potential (CAP) is a purely neural component of the cochlea's response to sound, and may provide information regarding the existing neural substrate in cochlear implant (CI) subjects that can help account for variance in speech perception outcomes. BACKGROUND: Measurement of the "total response" (TR), or sum of the magnitudes of spectral components in the ongoing responses to tone bursts across frequencies, has been shown to account for 40 to 50% of variance in speech perception outcomes. The ongoing response is composed of both hair cell and neural components. This correlation may be improved with the addition of the CAP. METHODS: Intraoperative round window electrocochleography (ECochG) was performed in adult and pediatric CI subjects (n = 238). Stimuli were tones of different frequencies (250 Hz-4 kHz) at 90 dB nHL. The CAP was assessed in two ways, as an amplitude and with a scaling factor derived from a function fitted to the response. The results were correlated with consonant-nucleus-consonant (CNC) word scores at 6 months post-implantation (n = 51). RESULTS: Only about half of the subjects had a measurable CAP at any frequency. The CNC word scores correlated weakly with both amplitude (r = 0.20, p < 0.001) and scaling factor (r = 0.25, p < 0.01). In contrast, the TR alone accounted for 43% of the variance, and addition of either CAP measurement in multiple regression did not account for additional variance. CONCLUSIONS: The underlying pathology in CI patients causes the CAP to be often absent and highly variable when present. The TR is a better predictor of speech perception outcomes than the CAP.

Effects of an EEG biofeedback protocol on a mixed substance abusing population.

UNLABELLED: This study examined whether an EEG biofeedback protocol could improve outcome measures for a mixed substance abusing inpatient population. METHOD: One hundred twenty-one volunteers undergoing an inpatient substance abuse program were randomly assigned to the EEG biofeedback or control group. EEG biofeedback included training in Beta and SMR to address attentional variables, followed by an alpha-theta protocol. Subjects received a total of 40 to 50 biofeedback sessions. The control group received additional time in treatment equivalent to experimental procedure time. The Test of Variables of Attention (TOVA), and MMPI, were administered with both tester and subject blind as to group placement to obtain unbiased baseline data. Treatment retention and abstinence rates as well as psychometric and cognitive measures were compared. RESULTS: Experimental subjects remained in treatment significantly longer than the control group (p <0.005). Of the experimental subjects completing the protocol, 77% were abstinent at 12 months, compared to 44% for the controls. Experimental subjects demonstrated significant improvement on the TOVA (p<.005) after an average of 13 beta-SMR sessions. Following alpha-theta training, significant differences were noted on 5 of the 10 MMPI-2 scales at the p<.005 level. CONCLUSIONS: This protocol enhanced treatment retention, variables of attention, and abstinence rates one year following treatment.