Hypoglossal nerve stimulation therapy on peripheral arterial tonometry in obstructive sleep apnea: a pilot study.

PURPOSE: Hypoglossal nerve stimulation (HGNS) is being increasingly utilized in the setting of moderate-severe obstructive sleep apnea (OSA). While moderate-severe OSA confers excess cardiovascular risk, the impact of HGNS on cardiovascular requires further investigation. With the advent of peripheral arterial tonometry (PAT), one can non-invasively study real-time changes to the autonomic nervous system. This study evaluates the effect of HGNS therapy on autonomic output, using PAT-integrated polysomnography. METHODS: Subjects included adult patients undergoing 2-month post-operative HGNS titration studies with PAT-integrated polysomnography. Apneic and hypopneic events with arousal during stage 2 sleep were identified at increasing levels of stimulation. With each event, PAT signal attenuations were recorded, processed, and analyzed. RESULTS: Nine subjects were enrolled, and eight met inclusion criteria (mean age 67.8 ± 12.4 years; 50% female). The PAT signal did not significantly change before and during stimulation (mean pre-stimulation 43.4 ± 1.7, mean intra-stimulation 41.1 ± 22.5, p = 0.53) in any patient. The ratio of the PAT signal maximum and minimum amplitudes during sleep breathing events largely demonstrated very weak correlation (R2 = <0.12). Across all subjects, poor linear correlation was present between HGNS and PAT signal attenuation (R2 = 0.028) in both adjusted and unadjusted analyses. CONCLUSIONS: Using PAT-integrated polysomnography, PAT output does not appear to be affected by HGNS stimulation at clinical thresholds. These findings support the absence of autonomic system alterations by twelfth nerve stimulation and support the clinical use of PAT-based devices for post-HGNS monitoring. Larger studies examining hard cardiovascular endpoints with HGNS are needed.

Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis.

Inhibition of nitric oxide (NO) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor, and arginine, the NOS substrate. We carried out a community-based case-control study of Gambian children to determine whether ADMA and arginine homeostasis is disrupted during severe or uncomplicated malaria infections. Circulating plasma levels of ADMA and arginine were determined at initial presentation and 28 days later. Plasma ADMA/arginine ratios were elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children (p<0.0001 for each comparison). To test the hypothesis that DDAH1 is inactivated during Plasmodium infection, we examined DDAH1 in a mouse model of severe malaria. Plasmodium berghei ANKA infection inactivated hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue ADMA, elevated ADMA/arginine ratio in plasma, and decreased whole blood nitrite concentration. Loss of hepatic DDAH1 activity and disruption of ADMA/arginine homeostasis may contribute to severe malaria pathogenesis by inhibiting NO synthesis.

Decreased Rate of Plasma Arginine Appearance in Murine Malaria May Explain Hypoargininemia in Children With Cerebral Malaria.

BACKGROUND: Plasmodium infection depletes arginine, the substrate for nitric oxide synthesis, and impairs endothelium-dependent vasodilation. Increased conversion of arginine to ornithine by parasites or host arginase is a proposed mechanism of arginine depletion. METHODS: We used high-performance liquid chromatography to measure plasma arginine, ornithine, and citrulline levels in Malawian children with cerebral malaria and in mice infected with Plasmodium berghei ANKA with or without the arginase gene. Heavy isotope-labeled tracers measured by quadrupole time-of-flight liquid chromatography-mass spectrometry were used to quantify the in vivo rate of appearance and interconversion of plasma arginine, ornithine, and citrulline in infected mice. RESULTS: Children with cerebral malaria and P. berghei-infected mice demonstrated depletion of plasma arginine, ornithine, and citrulline. Knock out of Plasmodium arginase did not alter arginine depletion in infected mice. Metabolic tracer analysis demonstrated that plasma arginase flux was unchanged by P. berghei infection. Instead, infected mice exhibited decreased rates of plasma arginine, ornithine, and citrulline appearance and decreased conversion of plasma citrulline to arginine. Notably, plasma arginine use by nitric oxide synthase was decreased in infected mice. CONCLUSIONS: Simultaneous arginine and ornithine depletion in malaria parasite-infected children cannot be fully explained by plasma arginase activity. Our mouse model studies suggest that plasma arginine depletion is driven primarily by a decreased rate of appearance.

Microvascular oxygen consumption during sickle cell pain crisis.

Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94] -ΔHbO2/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -ΔHbO2/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT01568710.

The Effect of COVID-19 Shelter-in-Place Orders on Pediatric Craniofacial Trauma.

Objectives: To investigate the impacts of the shelter-in-place orders on the injury patterns among children with craniofacial trauma. Materials and Methods: Pediatric (<18 years old) craniofacial trauma cases presenting to a regional level I trauma center 1 year before and after the initiation of Washington's shelter-in-place order were retrospectively reviewed. Demographic and injury-related variables were recorded, and bivariate and logistic regression analyses were computed. Results: One hundred nineteen children were evaluated over 2-year period (46 pre- and 73 post-shelter-in-place and were comparable in age, gender, and ethnicity (p ≥ 0.17)). The distribution of injury mechanisms between pre- and post-shelter-in-place were significantly different (p = 0.02), with the largest proportional increase in falls (10.5%) and had higher rates of associated brain injury (p ≤ 0.02). After adjusting for effect modifiers and confounders, children presenting during the post-shelter-in-place period were more likely to have associated brain injuries (odds ratio 3.4, 95% confidence interval: 1.11-10.6, p = 0.03). Conclusions: Among pediatric craniofacial injury cases, the shelter-in-place order was associated with a higher likelihood of brain injury and significant changes in injury mechanisms, with a higher proportion of falls.

Patient Factors and Preferences in Choosing Sleep Surgery for Obstructive Sleep Apnea: A Qualitative Study.

OBJECTIVE: There are several obstructive sleep apnea (OSA) treatment options available to patients, including surgery and less invasive therapies. Little is known about the factors that influence patient preferences for treatment. We aimed to understand factors influencing patient experience and decision making for undergoing sleep surgery. STUDY DESIGN: Retrospective qualitative study. SETTING: Tertiary sleep surgery clinic. METHODS: We conducted semistructured interviews with adults who previously underwent any nasal and/or pharyngeal sleep surgery. We asked open-ended questions about their decision-making process within a preconceived thematic framework of chief OSA symptoms, expectations for recovery, and sources of information. The interviews were audio recorded and transcribed, and content was analyzed for defined, emergent, and prevalent themes. RESULTS: Ten patients were interviewed from December 11, 2020 through January 29, 2021. Six patients underwent nasal surgery, 1 underwent pharyngeal surgery, and 3 underwent staged nasal and pharyngeal procedures. All patients were beyond the acute recovery phase. Reasons for pursuing surgical consultation varied from sleep apnea burden to external factors, such as recommendations from significant others. Duration of sleep surgery consideration varied from months to years. Major concerns about sleep surgery involved anesthesia and postoperative pain. External factors influencing patients' decisions to pursue sleep surgery included family and friend support. Postoperative outcomes of surgery included patient satisfaction with decision for surgery, given OSA improvements. CONCLUSION: Understanding patient factors that influence decision making for sleep surgery may guide clinicians in patient-centered counseling that engages patients in decision making, aligning with clinical symptoms and patient preferences.

A Validated 3D Printed Laryngeal Suturing Simulator for Endoscopic Laryngeal Cleft Repair.

OBJECTIVES: Endoscopic laryngeal cleft repair (ELCR) with endolaryngeal suturing is an advanced surgical skill. This study objective was to assess the validity of 3-dimensionally (3D) printed laryngeal suturing simulator for ELCR. STUDY DESIGN: Development and validation of a simulator for ELCR. METHODS: An ELCR model was developed using 3D printed and readily available materials. Participants were surveyed before and after a simulation session using five-point Likert scale questions. Performance data was assessed using blinded expert video review and rated using a novel objective structured assessment of technical skills (OSATS) for endoscopic laryngeal suturing. RESULTS: Twenty-one participants ranging from residents to attendings completed the simulation session. Survey respondents reported on a five-point Likert scale that the model was "easy to use" and "quite realistic" (both mean of 4). Confidence improved significantly in 86% of participants (p < 0.01). Overall OSATS scores (out of a total of 55) showed a median improvement in technical skills of 11.7 points (p = 0.004). OSATS demonstrated good intra-rater (κ = 0.689 and 0.677) and moderate inter-rater (κ = 0.573) reliability. Completion times improved from the first to the last suture by a median time of 512 to 350 s (decrease of 202 s, p = 0.002). Participants with no prior ELCR experience improved more than those with in vivo experience. CONCLUSION: This study demonstrates the validity of a simulator utilizing 3D printed larynges for ELCR. A novel OSATS for endoscopic laryngeal suturing was successfully implemented. Confidence, technical skills, and completion times improved with the use of the model across a variety of participants. Laryngoscope, 133:785-791, 2023.

Barriers and communication behaviors impacting referral to sleep surgery: qualitative patient perspectives.

STUDY OBJECTIVES: Physician-patient interactions influence the immediate encounter and leave lasting impressions for future health care encounters. We aimed to understand patient experiences and decision-making for considering sleep surgery, in terms of barriers and communication behaviors that facilitate or hinder referral for consideration of sleep surgery management of obstructive sleep apnea (OSA) when continuous positive airway pressure (CPAP) therapy has failed. METHODS: We employed qualitative methods, using semistructured interviews of adults with OSA who presented for sleep surgery consultation after unsatisfactory therapy with CPAP. Open-ended questions traced symptoms and progression of sleep apnea burden, trials of noninvasive OSA therapies, outcomes, and patient expectations and concerns. The interviews were audio-recorded, transcribed, and analyzed using content analysis to identify themes. RESULTS: Ten adult patients with OSA were enrolled March through April 2021 and reached predominant thematic saturation. Barriers to sleep surgery consultation included: (1) delays in OSA diagnosis due to limited OSA awareness among patients or primary providers and patients' perceived inconvenience of sleep testing, (2) patients faulted for slow progress, (3) patient-reported lack of urgency by providers in troubleshooting noninvasive management options, (4) scheduling delays and waitlists, and (5) cost. Patients were receptive to noninvasive treatment options, but inadequate improvement led to frustration after multiple encounters. Patients appreciated empathetic providers who shared information through transparent and understandable explanations and who presented multiple treatment options. CONCLUSIONS: Experiences of patients with OSA highlight the need for shared decision-making through improved communication of unresolved concerns and alternative management options, including timely referral for sleep surgery consultation when indicated. CITATION: Ikeda AK, McShay C, Marsh R, et al. Barriers and communication behaviors impacting referral to sleep surgery: qualitative patient perspectives. J Clin Sleep Med. 2023;19(1):111-117.

Increased brain microvascular hemoglobin concentrations in children with cerebral malaria.

Brain swelling is associated with death from cerebral malaria, but it is unclear whether brain swelling is caused by cerebral edema or vascular congestion-two pathological conditions with distinct effects on tissue hemoglobin concentrations. We used near-infrared spectroscopy (NIRS) to noninvasively study cerebral microvascular hemoglobin concentrations in 46 Malawian children with cerebral malaria. Cerebral malaria was defined by the presence of the malaria parasite Plasmodium falciparum on a blood smear, a Blantyre coma score of 2 or less, and retinopathy. Children with uncomplicated malaria (n = 33) and healthy children (n = 29) were enrolled as comparators. Cerebral microvascular hemoglobin concentrations were higher among children with cerebral malaria compared with those with uncomplicated malaria [median (25th, 75th): 145.2 (95.2, 190.0) µM versus 82.9 (65.7, 105.4) µM, P = 0.008]. Cerebral microvascular hemoglobin concentrations correlated with brain swelling score determined by MRI (r = 0.37, P = 0.03). Fluctuations in cerebral microvascular hemoglobin concentrations over a 30-min time period were characterized using detrended fluctuation analysis (DFA). DFA determined self-similarity of the cerebral microvascular hemoglobin concentration signal to be lower among children with cerebral malaria compared with those with uncomplicated malaria [0.63 (0.54, 0.70) versus 0.91 (0.82, 0.94), P < 0.0001]. The lower self-similarity of the hemoglobin concentration signal in children with cerebral malaria suggested impaired regulation of cerebral blood flow. The elevated cerebral tissue hemoglobin concentration and its correlation with brain swelling suggested that excess blood volume, potentially due to vascular congestion, may contribute to brain swelling in cerebral malaria.

Evidence-Based Medicine in Otolaryngology Part 16: Qualitative and Quantitative Methods-Contrasting and Complementary Approaches.

Qualitative methods have been increasingly applied in our literature, providing richness to data and incorporating the nuances of patient and family perspectives. These qualitative research techniques provide breadth and depth beyond what can be gleaned through quantitative methods alone. When both quantitative and qualitative approaches are coupled, their findings provide complementary information which can further substantiate study conclusions. We thus aim to provide insight into qualitative and quantitative methods in comparison and contrast to each other, as well as guidance on when each approach is most apt. In relation, we also describe mixed methods and the theory supporting their framework. In doing so, we provide the foundation for an ensuing, more detailed exposition of qualitative methods.

LeFort Fractures.

Consultations for management of facial fractures in the emergency setting are not uncommon for the oral maxillofacial surgeon, otolaryngologist, and/or plastic surgeon. This necessitates a knowledge foundation and working understanding of the evaluation, assessment, and timely management. Here, we will focus on the workup and management of LeFort fractures.

Management of patients with unilateral microtia and aural atresia: recent advances and updates.

PURPOSE OF REVIEW: The management of patients with unilateral microtia and aural atresia is complex. Recent literature suggests significant strides in hearing habilitation and ear reconstruction. RECENT FINDINGS: Several options of hearing management are available and are associated with improved outcomes. Timelines for hearing habilitation and ear reconstruction vary by institution. We offer our timeline as a reference. Three dimensional (3D) printed models are increasingly used for training and reconstruction. Bioprinting is on the horizon, though safety and effectiveness studies are pending. Lastly, application of qualitative methods has provided a foundation on which to improve communication between physicians and patients and their families. Better understanding of the patient and family experiences will provide opportunities to target interventions to improve care. SUMMARY: Current developments include expanding options for hearing management, changing approaches to timing of atresiaplasty, utilization of 3D printed models, and focus on patient and family experience to improve reconstructive outcomes.

Risk Factors for Rhinosinusitis After Endoscopic Transsphenoidal Adenomectomy.

OBJECTIVE: Patients undergoing endoscopic transsphenoidal adenomectomy (eTSA) for pituitary tumors are at risk for postoperative complications, including rhinosinusitis. We aimed to determine if preoperative sinonasal disease is a risk factor for postoperative rhinosinusitis (PRS). STUDY DESIGN: Retrospective review. SETTING: Tertiary academic center in U.S. SUBJECTS AND METHODS: Patients with a diagnosis of pituitary adenoma who underwent eTSA between 2007-2016. PRS patients were matched to non-PRS patients or sex, age, tumor size, skull base reconstruction with intranasal tissue grafting, and concurrent septoplasty. Groups were statistically analyzed for potential preoperative risk factors of sinonasal disease (patient-reported, radiographic, endoscopic). RESULTS: 49 of 987 patients who underwent eTSA developed PRS (44.9% male, 71.4% Caucasian, mean age 49.3y). On analysis of individual risk factors, there was a significantly higher proportion of patients with a history of prior sinonasal surgery in the PRS group than the non-PRS group (25.5% vs. 6.5%, p = 0.01); however, this group difference became insignificant on multivariate analysis. There were no significant group differences with regard to history of sinus infections, nasal symptoms, seasonal allergies, radiographic abnormalities, or sinonasal disease on endoscopy. CONCLUSION: This is the first study to investigate preoperative sinonasal disease as a risk factor for PRS after eTSA. The risk factors considered did not demonstrate definitive risk for PRS, although a history of prior sinonasal surgery should be investigated further.

Remodeling of the Paradoxical Middle Turbinate: Preserving Function While Gaining Access.

Background Endoscopic sinus surgery is performed for many reasons, most commonly for chronic rhinosinusitis refractory to medical treatment. A paradoxical middle turbinate is an anatomic variant that can hinder endoscopic access to the sinuses. No publication has addressed how to surgically treat a paradoxical middle turbinate. Method We present a basic endoscopic surgical approach to conservatively resect a paradoxical middle turbinate in order to improve access to the middle meatus and the sinuses while preserving support and function. Conclusion Conservative remodeling of the paradoxical middle turbinate can provide access to the sinuses while maintaining a significant portion of the middle turbinate.

Macrolide-associated sensorineural hearing loss: A systematic review.

OBJECTIVES: To investigate the potential association of macrolide antibiotics with sensorineural hearing loss (SNHL) and which agents and dosage may be related. To evaluate whether an optimal treatment exists for reversing SNHL that occurs after macrolide therapy. STUDY DESIGN: Systematic review of the literature. METHODS: Computerized (PubMed, EMBASE, Cochrane Library) and manual searches were performed to identify human studies of all ages (patients) who received macrolides (intervention, with or without control) and documented SNHL (outcome). All study designs were assessed. Extracted data included macrolide regimen details, as well as the timing, severity, and reversibility of SNHL with drug cessation alone or with additional medical intervention. Study designs and the associated risk of bias were assessed. RESULTS: The 44 publications (3 prospective, 41 retrospective) that met these criteria described 78 cases of audiometrically confirmed SNHL. SNHL was associated with oral and intravenous macrolide administration at standard and elevated doses. SNHL was irreversible in six cases, despite macrolide cessation (n = 5) and oral steroid treatment (n = 1). Irreversible SNHL was observed following 2 to 3 days of exposure. SNHL was reversible with macrolide cessation alone in 70 cases. In two cases, macrolide cessation coupled with oral steroid administration restored hearing. Reversible cases improved within hours to days. Nine studies also described 42 cases of subjective patient-reported hearing loss. Limitations in the data arose from study design, related comorbidities, and concomitant drug administration. CONCLUSION: SNHL may follow macrolide exposure, even at standard oral doses. Further research is needed to understand the incidence, prevalence, and biological mechanism of its ototoxicity. Laryngoscope, 128:228-236, 2018.

Evidence-Based Medicine in Otolaryngology, Part 8: Shared Decision Making-Impact, Incentives, and Instruments.

In our previous installment, we introduced shared decision making (SDM) as a collaborative process in which patients, families, and clinicians develop a mutually optimized treatment plan when more than 1 reasonable treatment option exists. In this subsequent installment of our Evidence-Based Medicine in Otolaryngology Series, we expand on the topic of SDM, including the related current state of clinical decision making, the impact of SDM on health care utilization and patient satisfaction, the potential role of system and society changes, the experience with SDM as it relates to race and ethnicity, existing financial incentives, and the validated instruments that assess the extent to which SDM occurs.

Evidence-Based Medicine in Otolaryngology Part 7: Introduction to Shared Decision Making.

Shared decision making (SDM) is a collaborative process in which patients, families, and clinicians develop a mutually agreed upon treatment plan when more than one reasonable treatment option exists. This cooperative engagement fosters improvements in patient satisfaction, disease management, and outcomes and also has the capacity to promote evidence-based care. Thus, this seventh installment of our Evidence-Based Medicine in Otolaryngology series focuses on SDM. We introduce SDM, including its potential to reduce decisional conflict and decisional regret, when it should be used, its potential benefits, barriers to implementation, and its role in the management of chronic disease and otolaryngological conditions.

Intranasal Steroid Use for Otitis Media with Effusion: Ongoing Opportunities for Quality Improvement.

Objectives Our objectives were (1) to assess patterns of intranasal steroid administration when otitis media with effusion (OME) has been diagnosed in children, (2) to investigate whether usage varies according to visit setting, and (3) to determine if practice gaps are such that quality improvement could be tracked. Study Design Cross-sectional analysis of an administrative database. Subjects and Methods National Ambulatory and Hospital Ambulatory Medical Care Surveys, 2005 to 2012; univariate, multivariate, and stratified analyses of intranasal steroid usage were performed. The primary outcome was intranasal steroid administration, and the primary predictor was a diagnosis of OME. The impact of location of service was also analyzed. Results Data representing 1,943,177,903 visits demonstrated that intranasal steroids were administered in 10.0% of visits in which OME was diagnosed, in comparison to 3.5% of visits in which OME was not diagnosed (univariate odds ratio, 3.07; 95% confidence interval [CI], 1.85-5.08; P < .001). After adjusting for age, sex, race/ethnicity, and other confounding conditions, multivariate analysis demonstrated that OME remained associated with an increase in intranasal steroid usage (odds ratio, 3.58; 95% CI, 1.60-8.01; P = .002). This practice pattern was more prevalent in the ambulatory office setting (risk difference 6.6%, P < .001) and less seen in a hospital-based office or emergency department. Conclusion Despite randomized controlled trials showing a lack of efficacy for isolated OME, nasal steroids continue to be used in treating children with OME in the United States. Related quality improvement opportunities to prevent usage of an ineffective treatment exist.