Factors Associated With Otolaryngologists Performing Tracheotomy.

Importance: Tracheotomies are frequently performed by nonotolaryngology services. The factors that determine which specialty performs the procedure are not defined in the literature but may be influenced by tracheotomy approach (open vs percutaneous) and other clinicodemographic factors. Objective: To evaluate demographic and clinical characteristics associated with tracheotomies performed by otolaryngologists compared with other specialists and to differentiate those factors from factors associated with use of open vs percutaneous tracheotomy. Design, Setting, and Participants: This multicenter, retrospective cohort study included patients aged 18 years or older who underwent a tracheotomy for cardiopulmonary failure at 1 of 8 US academic institutions between January 1, 2013, and December 31, 2016. Data were analyzed from September 2022 to July 2023. Exposure: Tracheotomy. Main Outcomes and Measures: The primary outcome was factors associated with an otolaryngologist performing tracheotomy. The secondary outcome was factors associated with use of the open tracheotomy technique. Results: A total of 2929 patients (mean [SD] age, 57.2 [17.2] years; 1751 [59.8%] male) who received a tracheotomy for cardiopulmonary failure (652 [22.3%] performed by otolaryngologists and 2277 [77.7%] by another service) were analyzed. Although 1664 of all tracheotomies (56.8%) were performed by an open approach, only 602 open tracheotomies (36.2%) were performed by otolaryngologists. Most tracheotomies performed by otolaryngologists (602 of 652 [92.3%]) used the open technique. Multivariable regression analysis revealed that self-reported Black race (odds ratio [OR], 1.89; 95% CI, 1.52-2.35), history of neck surgery (OR, 2.71; 95% CI, 2.06-3.57), antiplatelet and/or anticoagulation therapy (OR, 1.74; 95% CI, 1.29-2.36), and morbid obesity (OR, 1.54; 95% CI, 1.24-1.92) were associated with greater odds of an otolaryngologist performing tracheotomy. In contrast, history of neck surgery (OR, 1.36; 95% CI, 0.96-1.92), antiplatelet and/or anticoagulation therapy (OR, 0.80; 95% CI, 0.56-1.14), and morbid obesity (OR, 0.94; 95% CI, 0.74-1.19) were not associated with undergoing open tracheotomy when performed by any service, and Black race (OR, 0.56; 95% CI, 0.44-0.71) was associated with lesser odds of an open approach being used. Age-adjusted Charlson Comorbidity Index score greater than 4 was associated with greater odds of both an otolaryngologist performing tracheotomy (OR, 1.26; 95% CI, 1.03-1.53) and use of the open tracheotomy technique (OR, 1.48, 95% CI, 1.21-1.82). Conclusions and Relevance: In this study, otolaryngologists were significantly more likely than other specialists to perform a tracheotomy for patients with history of neck surgery, morbid obesity, and ongoing anticoagulation therapy. These findings suggest that patients undergoing tracheotomy performed by an otolaryngologist are more likely to present with complex and challenging clinical characteristics.

Accuracy of Ultrasound Imaging for Etiology of New-Onset Painless Jaundice.

PURPOSE: Ultrasound (US) is considered a first-line study for painless jaundice. However, in our hospital system, patients with new-onset painless jaundice often have a contrast-enhanced computed tomography (CECT) or magnetic resonance cholangiopancreatography (MRCP) regardless of the sonographic findings. Thus, we investigated the accuracy of US for detection of biliary dilatation in patients with new-onset painless jaundice. METHODS: Our electronic medical record was searched from January 1, 2012, to January 1, 2020, for adult patients with new-onset painless jaundice. Presenting complaint/setting, laboratory values, imaging studies/findings, and final diagnoses were recorded. Patients with pain or known liver disease were excluded. A gastrointestinal physician reviewed the laboratory values/chart to classify the type of suspected obstruction. Two radiologists blindly re-reviewed the US scans, and κ between the radiologists was calculated. Fisher exact test and the 2-sample t test were used for statistical analysis. RESULTS: Three hundred sixty patients presented with jaundice (>3 mg/dL), of whom 68 met the inclusion criteria (no pain and no known liver disease). Laboratory values had an overall accuracy of 54%, but were accurate in 87.5% and 85% for obstructing stones/pancreaticobiliary cancer. Ultrasound demonstrated overall accuracy of 78%, but only 69% for pancreaticobiliary cancer and 12.5% for common bile duct stone. Seventy-five percent of the patients underwent follow-up CECT or MRCP regardless of presenting setting. In the emergency department or inpatient setting, 92% of the patients underwent CECT or MRCP regardless of US, and 81% had follow-up CECT or MRCP within 24 hours. CONCLUSION: A US-first strategy in the setting of new-onset painless jaundice is accurate only 78% of the time. In practice, US was almost never a stand-alone imaging examination in patients presenting to the emergency department or inpatient setting with new-onset painless jaundice, no matter the suspected diagnosis based on clinical and laboratory grounds or on the US findings themselves. However, for milder elevations of unconjugated bilirubin (suspicious for Gilbert disease) in the outpatient setting, a US demonstrating lack of biliary dilatation was often a definitive study for exclusion of pathology.

Clinicodemographic Predictors of Tracheotomy Tube Size and Decannulation: A Multiinstitutional Retrospective Cohort Study on Tracheotomy.

OBJECTIVE: We aimed to discern clinico-demographic predictors of large (≥8) tracheostomy tube size placement, and, secondarily, to assess the effect of large tracheostomy tube size and other parameters on odds of decannulation before hospital discharge. SUMMARY OF BACKGROUND DATA: Factors determining choice of tracheostomy tube size are not well-characterized in the current literature, despite evidence linking large tracheostomy tube size with posttracheotomy tracheal stenosis. The effect of tracheostomy tube size on timing of decannulation is also unknown, an important consideration given reported associations between endotracheal tube size and probability of failed extubation. METHODS: We collected information pertaining to patients who underwent tracheotomy at 1 of 10 U.S. health care institutions between 2010 and 2019. Tracheostomy tube size was dichotomized (≥8 and <8). Multivariable logistic regression models were fit to identify predictors of (1) large tracheostomy tube size, and (2) decannulation before hospital discharge. RESULTS: The study included 5307 patients, including 2797 (52.7%) in the large tracheostomy cohort. Patient height (odds ratio [OR] = 1.060 per inch; 95% confidence interval [CI] 1.041-1.070) and obesity (1.37; 95% CI 1.1891.579) were associated with greater odds of large tracheostomy tube; otolaryngology performing the tracheotomy was associated with significantly lower odds of large tracheostomy tube (OR = 0.155; 95% CI 0.131-0.184). Large tracheostomy tube size (OR = 1.036; 95% CI 0.885-1.213) did not affect odds of decannulation. CONCLUSIONS: Obesity was linked with increased likelihood of large tracheostomy tube size, independent of patient height. Probability of decannulation before hospital discharge is influenced by multiple patient-centric factors, but not by size of tracheostomy tube.

Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination.

BACKGROUND: Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS-resident memory T (TRM) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown. METHODS: Here, we examined immune cells within the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation and genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss. RESULTS: Profiling of host transcriptome immune cells at 25 days post-infection in mice revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in TRM cell biology, was identified as critically regulating CXCR6 expressing CD8+ TRM cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highly expressed by all myeloid cells, and its unique receptor, CXCR6, is highly expressed on all CD8+ T cells. Using genetic and pharmacological approaches, we demonstrate that CXCL16/CXCR6 not only is required for the maintenance of WNV-specific CD8 TRM cells in the post-infectious CNS, but also contributes to their expression of TRM cell markers. Moreover, CXCR6+CD8+ T cells are required for glial activation and ongoing synapse elimination. CONCLUSIONS: We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8+ T cells that maintains forebrain TRM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 in mice during recovery may reduce CNS CD8+ TRM cells.

Using a checklist within simulation improves trainees' confidence on ward rounds.

Ward rounds are integral to maintaining patient safety in everyday clinical care. Junior doctors are often expected to conduct independent rounds on graduation, but many feel ill-equipped to do so. We developed a safety checklist and simulation sessions to improve junior-led ward round practice at one district general hospital. We found that embedding a checklist within simulation is an effective way to teach ward round skills and increase confidence among undergraduate and postgraduate medical trainees.

Olfactory exposure to late-pregnant and lactating mice causes stress-induced analgesia in male mice.

In an attempt to improve reproducibility, more attention is being paid to potential sources of stress in the laboratory environment. Here, we report that the mere proximity of pregnant or lactating female mice causes olfactory-mediated stress-induced analgesia, to a variety of noxious stimuli, in gonadally intact male mice. We show that exposure to volatile compounds released in the urine of pregnant and lactating female mice can themselves produce stress and associated pain inhibition. This phenomenon, a novel form of female-to-male chemosignaling, is mediated by female scent marking of urinary volatiles, such as n-pentyl-acetate, and likely signals potential maternal aggression aimed at defending against infanticide by stranger males.

Long-term male-specific chronic pain via telomere- and p53­mediated spinal cord cellular senescence.

Mice with experimental nerve damage can display long­lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53­mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53­positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male­specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male­specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53­specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male­specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.

Decreased antiviral immune response within the central nervous system of aged mice is associated with increased lethality of West Nile virus encephalitis.

West Nile virus (WNV) is an emerging pathogen that causes disease syndromes ranging from a mild flu-like illness to encephalitis. While the incidence of WNV infection is fairly uniform across age groups, the risk of lethal encephalitis increases with advanced age. Prior studies have demonstrated age-related, functional immune deficits that limit systemic antiviral immunity and increase mortality; however, the effect of age on antiviral immune responses specifically within the central nervous system (CNS) is unknown. Here, we show that aged mice exhibit increased peripheral organ and CNS tissue viral burden, the latter of which is associated with alterations in activation of both myeloid and lymphoid cells compared with similarly infected younger animals. Aged mice exhibit lower MHCII expression by microglia, and higher levels of PD1 and lower levels of IFNγ expression by WNV-specific CD8+ T cells in the CNS and CD8+ CD45+ cells. These data indicate that the aged CNS exhibits limited local reactivation of T cells during viral encephalitis, which may lead to reduced virologic control at this site.

Spectral arc length as a method to quantify pharyngeal high-resolution manometric curve smoothness.

BACKGROUND: Pharyngeal high-resolution manometry (HRM) has emerged over the last decade as a valuable assessment tool for oropharyngeal dysphagia. Data analysis thus far has focused primarily on measures of pressure and duration within key anatomic regions. We apply spectral arc length (SPARC), a dimensionless metric for quantifying smoothness felt to indirectly reflect neuromuscular coordination, as a new method of describing manometric curves. We then use it to distinguish swallows from healthy subjects and those with dysphagia related to stroke. METHODS: Previously collected pharyngeal HRM data from eight subjects with history of stroke and eight age- and sex-matched controls were reviewed. Receiver operating characteristic (ROC) analysis was used to optimize SPARC inputs. SPARC was then computed for the velopharynx, tongue base, hypopharynx, and upper esophageal sphincter (UES), and the values were compared between the two subject groups. RESULTS: Optimized parameter settings yielded an ROC curve with area under the curve (AUC) of 0.953. Mean SPARC values differed between control and stroke subjects for the velopharynx (t = 3.25, p = 0.0058), tongue base (t = 4.77, p = 0.0003), and hypopharynx (t = 2.87, p = 0.0124). Values were similar for the UES (t = 0.43, p = 0.671). CONCLUSIONS: In this preliminary study, SPARC analysis was applied to distinguish control from post-stroke subjects. Considering alternative methods of analyzing pharyngeal HRM data may provide additional insight into the pathophysiology of dysphagia beyond what can be gleaned from measures of pressure and duration alone.

Cage-lid hanging behavior as a translationally relevant measure of pain in mice.

ABSTRACT: The development of new analgesic drugs has been hampered by the inability to translate preclinical findings to humans. This failure is due in part to the weak connection between commonly used pain outcome measures in rodents and the clinical symptoms of chronic pain. Most rodent studies rely on the use of experimenter-evoked measures of pain and assess behavior under ethologically unnatural conditions, which limits the translational potential of preclinical research. Here, we addressed this problem by conducting an unbiased, prospective study of behavioral changes in mice within a natural homecage environment using conventional preclinical pain assays. Unexpectedly, we observed that cage-lid hanging, a species-specific elective behavior, was the only homecage behavior reliably impacted by pain assays. Noxious stimuli reduced hanging behavior in an intensity-dependent manner, and the reduction in hanging could be restored by analgesics. Finally, we developed an automated approach to assess hanging behavior. Collectively, our results indicate that the depression of hanging behavior is a novel, ethologically valid, and translationally relevant pain outcome measure in mice that could facilitate the study of pain and analgesic development.

Pressure abnormalities in patients with Zenker's diverticulum using pharyngeal high-resolution manometry.

OBJECTIVES: Zenker's diverticulum is associated with reduced cricopharyngeal compliance and abnormal intrabolus pressure. However, it is unclear how the pharynx compensates for these deficits. Developments in manometric technology have improved our ability to capture pharyngeal pressure events. This study aims to describe the pharyngeal-upper esophageal sphincter (UES) pressure profile during swallowing in patients with Zenker's diverticulum. METHODS: High-resolution manometry was performed on 11 patients with symptomatic Zenker's diverticulum and 11 age- and sex-matched healthy controls during 10 mL liquid swallowing tasks. Pharyngeal and UES pressure magnitudes, durations, and integrals were compared between patients and controls using independent t tests. Other manometric parameters, including residual UES pressure at the time of maximum tongue base pressure and pharyngeal-UES pressure gradient, were also evaluated. A case example using three-dimensional high-resolution manometry is presented. RESULTS: Compared with healthy controls, patients with Zenker's diverticulum exhibited pressure abnormalities in the UES region. While baseline and pre-opening maximum pressures were not different, residual pressures were elevated (P = .001). Pharyngeal-UES pressure gradients did not differ between the two groups. CONCLUSION: This study used high-resolution manometry to characterize pharyngeal pressure dynamics in patients with Zenker's diverticulum. The changes occurring at the cricopharyngeus appear to result in persistent UES pressurization during UES opening, rather than high tonic resting pressure. Pharyngeal-UES pressure gradients, critical to bolus passage, were also preserved in this patient population. LEVEL OF EVIDENCE: 3b.

Sex differences in cancer mechanisms.

We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab- and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.

Increased pain sensitivity and decreased opioid analgesia in T-cell-deficient mice and implications for sex differences.

The processing of pain in the central nervous system is now known to have an important immune component, including T cells of the adaptive immune system. T cells have been shown to release endogenous opioids, and although it is well known that opioids have effects on T-cell populations, very little attention has been given to the converse: how T cells may affect opioid regulation. We find here that, in addition to displaying significantly increased baseline pain sensitivity across various pain modalities, T-cell-deficient mice (CD-1 nude, Rag1 null mutant, and Cd4 null mutant) exhibit pronounced deficiencies in morphine inhibition of thermal or inflammatory pain. Nude mice are also deficient in endogenous opioid-mediated analgesia, exhibiting no stress-induced analgesia from restraint. The relevant T-cell subpopulation seems to be CD4 T cells because adoptive transfer of them but not CD8 cells into nude mice rescues both the pain and morphine analgesia phenotypes. As previously reported, we also observe a sex difference in CD-1 mice, with females requiring 2- to 3-fold more morphine than males to produce equal analgesia. Nude mice display no sex differences in morphine analgesia, and the sex difference is restored in nude mice of either sex receiving CD4 T cells from CD-1 donor male or female mice. These results suggest that CD4 T cells play an as yet unappreciated role in opioid analgesia and may be a driver of sex differences therein.

State of the Art: Role of the Dendritic Cell in Induction of Allograft Tolerance.

Despite decades of research, the induction and maintenance of long-term allograft tolerance without immunosuppression remains an elusive goal in the field of solid organ and cell transplantation. Immunosuppressive medications frequently prevent or minimize acute cellular rejection but have failed to halt antidonor antibody production and chronic organ rejection. Past efforts aimed at promoting lasting allograft tolerance have focused primarily on peripheral T-cell depletion, augmentation of regulatory T cells, or induction via simultaneous hematopoietic stem cell transplantation and facilitation of donor chimerism. So far, none of these methods have led to consistently safe, feasible and long lasting donor organ acceptance. Over the course of the past 4 decades, the study of a unique population of antigen-presenting cells known as dendritic cells has shown promise for breaking new ground in achieving indefinite allograft survival without immunosuppression and its associated adverse effects. In this review, we discuss the discovery and early investigations of dendritic cells and chronicle some of the key studies demonstrating their role in transplantation, particularly in indirect allorecognition, the immunologic pathway thought to drive chronic rejection and perhaps tolerance induction.

Methods for measuring swallowing pressure variability using high-resolution manometry.

Any movement performed repeatedly will be executed with inter-trial variability. Oropharyngeal swallowing is a complex sensorimotor action, and swallow-to-swallow variability can have consequences that impact swallowing safety. Our aim was to determine an appropriate method to measure swallowing pressure waveform variability. An ideal variability metric must be sensitive to known deviations in waveform amplitude, duration, and overall shape, without being biased by waveforms that have both positive and sub-atmospheric pressure profiles. Through systematic analysis of model waveforms, we found a coefficient of variability (CV) parameter on waveforms adjusted such that the overall mean was 0 to be best suited for swallowing pressure variability analysis. We then investigated pharyngeal swallowing pressure variability using high-resolution manometry data from healthy individuals to assess impacts of waveform alignment, pharyngeal region, and number of swallows investigated. The alignment that resulted in the lowest overall swallowing pressure variability was when the superior-most sensor in the upper esophageal sphincter reached half its maximum pressure. Pressures in the tongue base region of the pharynx were least variable and pressures in the hypopharynx region were most variable. Sets of 3 - 10 consecutive swallows had no overall difference in variability, but sets of 2 swallows resulted in significantly less variability than the other dataset sizes. This study identified variability in swallowing pressure waveform shape throughout the pharynx in healthy adults; we discuss implications for swallowing motor control.

Effect of Body Position on Pharyngeal Swallowing Pressures Using High-Resolution Manometry.

The effect of body position and gravitational pull on the complex pressure-driven process of pharyngeal swallowing remains unknown. Using high-resolution manometry (HRM), this study aims to identify positional adaptations of pharyngeal physiology by evaluating swallowing pressure patterns in a series of inverted body positions. Ten healthy adults each underwent swallowing tasks with pharyngeal HRM at six body positions using an inversion table (0°[upright], 45°, 90°[supine], 110°, 135°, and 180°[fully inverted]). Repeated measures ANOVA was used to assess impact of position on pressure parameters, and pharyngeal-UES pressure gradients translate. Velopharyngeal pressures varied by position (P < 0.001), with significantly higher pressures generated with inversion ≥90°, compared with upright and 45°. Change in position did not significantly affect common mesopharyngeal pressures or swallowing pressure durations. UES valving mechanisms were preserved during inversion, with subtle variations observed in integral pressures (P = 0.011). Pharyngeal-UES pressure gradients changed with position (P < 0.01), increasing with inversion > 90° compared to upright and 45°. Mechanisms of deglutition may differ with position and relative direction of gravity, particularly when at > 45° inclination. Increased palatal pressure is generated in the upside-down position to achieve nasopharyngeal closure and prevent regurgitation. While other classically measured pressures may not consistently differ with positioning, many individuals exhibit adaptations in pressure gradients when inverted, likely due to a combination of changes in pharyngeal driving force and UES opening mechanisms. Identification of these changes, relative to position, further builds on our understanding of the adaptability of the pharyngeal swallowing system.

T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice.

It has been reported consistently that many female chronic pain sufferers have an attenuation of symptoms during pregnancy. Rats display increased pain tolerance during pregnancy due to an increase in opioid receptors in the spinal cord. Past studies did not consider the role of non-neuronal cells, which are now known to play an important role in chronic pain processing. Using an inflammatory (complete Freund's adjuvant) or neuropathic (spared nerve injury) model of persistent pain, we observed that young adult female mice in early pregnancy switch from a microglia-independent to a microglia-dependent pain hypersensitivity mechanism. During late pregnancy, female mice show no evidence of chronic pain whatsoever. This pregnancy-related analgesia is reversible by intrathecal administration of naloxone, suggesting an opioid-mediated mechanism; pharmacological and genetic data suggest the importance of δ-opioid receptors. We also observe that T-cell-deficient (nude and Rag1-null mutant) pregnant mice do not exhibit pregnancy analgesia, which can be rescued with the adoptive transfer of CD4+ or CD8+ T cells from late-pregnant wild-type mice. These results suggest that T cells are a mediator of the opioid analgesia exhibited during pregnancy.SIGNIFICANCE STATEMENT Chronic pain symptoms often subside during pregnancy. This pregnancy-related analgesia has been demonstrated for acute pain in rats. Here, we show that pregnancy analgesia can produce a complete cessation of chronic pain behaviors in mice. We show that the phenomenon is dependent on pregnancy hormones (estrogen and progesterone), δ-opioid receptors, and T cells of the adaptive immune system. These findings add to the recent but growing evidence of sex-specific T-cell involvement in chronic pain processing.

Integrating the microbiota of the respiratory tract with the unified airway model.

The unified airway model has developed from indications that the upper and lower respiratory tracts share key elements of pathogenesis. These shared traits likely extend to similar niche characteristics that support bacterial communities, and as such, we suspect that similar microbes exist on upper and lower respiratory tract epithelium. Over the past decade and a half there have been significant improvements in microbiological identification and analysis due to the development of new molecular technologies, including next-generation sequencing. In this review, we provide an overview of the modern collection and sequencing methods involved in respiratory microbiota research, and outline the specific microbial communities that have been found to be associated with the healthy and diseased human respiratory tract. Demonstration of a remarkable similarity between the upper and lower respiratory tract in terms of microbiological presence adds further corroboration to the existence of a unified airway.

Pharyngeal swallowing pressures in the base-of-tongue and hypopharynx regions identified with three-dimensional manometry.

OBJECTIVES: This study aims to use three-dimensional (3D) high-resolution manometry to identify circumferential pressure patterns generated within the asymmetrical base-of-tongue and hypopharynx regions of the pharynx during deglutition. STUDY DESIGN: Case series. METHODS: Radial pressures in the regions of interest were evaluated during swallowing events in 12 healthy subjects using 3D high-resolution manometry. RESULTS: Repeated measures analysis of variance revealed asymmetrical pharyngeal clearance pressures in the base-of-tongue and hypopharynx regions during swallowing. A significant main effect of direction on pressure was found at the time point of average maximum pressure (P < 0.001) and for pressure integral (P < 0.001), with pressure primarily generated from the posterior direction. An interaction was noted between direction and location when comparing maximum directional pressures, regardless of time (P =0.045), highlighting the differences in anterior pressure production between regions. In contrast to the high posterior pressures produced in the base-of-tongue region, an anteroposterior dominant pressure pattern was observed in the hypopharynx. Pressure waveform complexity in the hypopharynx also is likely attributed to activity in the anterior and posterior directions. Symmetrical pressure generation was observed during intrabolus flow within the hypopharynx. CONCLUSION: This study shows that pressure is asymmetrically generated in the base-of-tongue and hypopharynx regions during swallowing of a 10-mL bolus, reflecting the complex anatomy within the pharynx. Understanding of these complex pressure patterns aids in the interpretation of high-resolution manometry and can help guide further study in the clinical assessment and treatment of pharyngeal pathology. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1989-1995, 2017.

Expiratory muscle strength training evaluated with simultaneous high-resolution manometry and electromyography.

OBJECTIVE: To examine feasibility of a simultaneous high-resolution pharyngeal manometry (HRM) and electromyography (EMG) experimental paradigm to detect swallowing-related patterns of palatal, laryngeal, and pharyngeal muscle activity during expiratory training. STUDY DESIGN: Technical report. METHODS: Simultaneous HRM, surface submental, and intramuscular EMG were acquired in two healthy participants during five tasks: 10-cc water swallow, maximum expiratory pressure (MEP) testing, and expiratory muscle strength training (EMST) at three pressure levels (sham, 50%, and 75% MEP). RESULTS: Experimental conditions were feasible. Velopharyngeal closing pressure, palate EMG activity, and pharyngeal EMG activity increased as expiratory load increased. In contrast, thyroarytenoid EMG activity was low during the expiratory task, consistent with glottic opening during exhalation. Submental EMG patterns were more variable during expiratory tasks. Intraluminal air pressures recorded with HRM were correlated with measured expiratory pressures and target valve-opening pressures of the EMST device. CONCLUSION: Results suggest that a simultaneous HRM/EMG/EMST paradigm may be used to detect previously unquantified swallowing-related muscle activity during EMST, particularly in the palate and pharynx. Our approach and initial findings will be helpful to guide future hypothesis-driven studies and may enable investigators to evaluate other muscle groups active during these tasks. Defining mechanisms of action is a critical next step toward refining therapeutic algorithms using EMST and other targeted treatments for populations with dysphagia and airway disorders. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:797-804, 2017.