Differences in Symptoms and Severity of Obstructive Sleep Apnea between Black and White Patients.

Rationale: Prior work suggests that Black patients have more severe obstructive sleep apnea (OSA) upon clinical presentation. However, the extent to which this may reflect differences in symptoms or other standard measures of OSA risk is unclear. Objectives: We assessed for racial disparities in OSA characteristics at time of initial clinical diagnosis. Methods: Data from 890 newly diagnosed patients with OSA at an urban academic sleep center were included in this analysis. All patients completed a standardized questionnaire on demographics and sleep-related symptoms and underwent laboratory polysomnography. Symptom severity at the time of evaluation was compared across race and sex. Results: Black men were underrepresented in the sleep lab, making up only 15.8% of the cohort and 31.3% of Black participants (P < 0.001). Despite this, Black men had the most severe OSA with a mean apnea hypopnea index of 52.4 ± 39.4 events/hour, compared with 39.0 ± 28.9 in White men, 33.4 ± 32.3 in Black women, and 26.2 ± 23.8 in White women (P < 0.001 for test of homogeneity). Black men also had the greatest burden of OSA symptoms with the highest mean Epworth Sleepiness Scale score (12.2 ± 5.9 versus 9.4 ± 5.2 in White men, 11.2 ± 5.9, in Black women, and 9.8 ± 5.6 in White women; P < 0.001). Compared with White men, Black men were 1.61 (95% CI [1.04-2.51]) times more likely to have witnessed apneas and 1.56 (95% CI [1.00-2.46]) times more likely to have drowsy driving at the time of OSA diagnosis. Conclusions: At the time of clinical diagnosis, Black men have greater disease severity, suggesting delay in diagnosis. Further, the greater burden of classic OSA symptoms suggests the delayed diagnosis of OSA in Black men is not due to atypical presentation. Further research is needed to identify why screening methods for OSA are not equitably implemented in the care of Black men.

Evaluation of Surgical Learning Curve Effect on Obstructive Sleep Apnea Outcomes in Upper Airway Stimulation.

OBJECTIVE: An increasing number of facilities offer Upper Airway Stimulation (UAS) with varying levels of experience. The goal was to quantify whether a surgical learning curve exists in operative or sleep outcomes in UAS. METHODS: International multi-center retrospective review of the ADHERE registry, a prospective international multi-center study collecting UAS outcomes. ADHERE registry centers with at least 20 implants and outcomes data through at least 6-month follow-up were reviewed. Cases were divided into two groups based on implant order (the first 10 or second 10 consecutive implants at a given site). Group differences were assessed using Mann-Whitney U-tests, Chi-squared tests, or Fisher's Exact tests, as appropriate. A Mann-Kendall trend test was used to detect if there was a monotonic trend in operative time. Sleep outcome equivalence between experience groups was assessed using the two one-sided tests approach. RESULTS: Thirteen facilities met inclusion criteria, contributing 260 patients. Complication rates did not significantly differ between groups (P = .808). Operative time exhibited a significant downward trend (P < .001), with the median operative time dropping from 150 minutes for the first 10 implants to 134 minutes for the subsequent 10 implants. The decrease in AHI from baseline to 12-month follow-up was equivalent between the first and second ten (22.8 vs 21.2 events/hour, respectively, P < .001). Similarly, the first and second ten groups had equivalent ESS decreases at 6 months (2.0 vs 2.0, respectively, P < .001). ESS outcomes remained equivalent for those with data through 12-months. CONCLUSIONS: Across the centers' first 20 implants, an approximately 11% reduction operative time was identified, however, no learning curve effect was seen for 6-month or 12-month AHI or ESS over the first twenty implants. Ongoing monitoring through the ADHERE registry will help measure the impact of evolving provider and patient specific characteristics as the number of implant centers increases.

DISE-PAP: a method for troubleshooting residual AHI elevation despite positive pressure therapy.

None: Despite excellent positive airway pressure (PAP) adherence, a subset of patients with obstructive sleep apnea experience residual elevation of the apnea-hypopnea index (AHI). Drug-induced sleep endoscopy during PAP application provides an opportunity to examine the anatomic effect of PAP therapy on the upper airway and to troubleshoot refractory residual AHI elevation. We present a patient who demonstrated persistent moderate-severe AHI elevation during titration polysomnogram and subsequent data download reports despite numerous mask refits, chin strap, positional modifications, and multiple pressure and mode adjustments in both the clinic and sleep laboratory settings. Drug-induced sleep endoscopy was performed with the flexible endoscope passed through the PAP circuit into the upper airway. Jaw laxity and associated mandibular retrusion at sleep onset was found to result in a complete fixed tongue base obstruction that PAP therapy, delivered via the patient's oronasal interface, was unable to overcome. Various strategies to overcome these obstacles are discussed.

Obstructive sleep apnea and CPAP therapy alter distinct transcriptional programs in subcutaneous fat tissue.

Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states, and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment's molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea-hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g. interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.

Dysfunctional hypoglossal nerve stimulator after electrical cardioversion: A case series.

OBJECTIVES/HYPOTHESIS: Upper airway stimulation has demonstrated marked improvements in apnea-hypopnea index, oxygen desaturation index, and quality-of-life measures in patients with moderate to severe obstructive sleep apnea (OSA) who cannot tolerate continuous positive airway pressure. Cardiac arrhythmias are common in patients with OSA and can require electrical cardioversion. We describe the first four reported cases of hypoglossal nerve stimulator (HGNS) dysfunction after electrical cardioversion and illustrate our operative approach to device troubleshooting and repair. STUDY DESIGN: Retrospective case series. METHODS: A retrospective review of 201 HGNS implantations performed at two academic institutions revealed four cases of HGNS device dysfunction after electrical cardioversion requiring surgical revision. Preoperative and postoperative device performance metrics and electrical cardioversion specifications were retrospectively assessed and compiled for this case series. The senior authors (R.J.S., M.S.B.) detail operative planning and approach for HGNS implantable pulse generator (IPG) replacement. RESULTS: At least two patients with HGNS device dysfunction had received cardioversion via anterolateral electrode pad placement. Three patients had received multiple shocks. All four patients experienced a change in device functionality or complete cessation of functionality after electrocardioversion. Operatively, each patient required replacement of the IPG, with subsequent intraoperative interrogation revealing proper device functionality. CONCLUSION: Counseling for patients with HGNS undergoing external electrical cardioversion should include possible device damage and need for operative replacement. Anteroposterior electrode pad placement should be considered for patients with HGNS who require electrocardioversion. Operative replacement of an HGNS system damaged by electrocardioversion begins with IPG replacement and intraoperative device interrogation. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1949-1953, 2019.

Risk of Postoperative Complications in Patients with Obstructive Sleep Apnea following Skull Base Surgery.

Objectives Obstructive sleep apnea (OSA) presents several challenges in skull base surgery, including increased intracranial pressure, worsened OSA with nasal packing, and avoidance of positive airway pressure (PAP) therapy postoperatively. The objective of this study was to examine the risk of postoperative complications in a skull base population with OSA in which PAP therapy is withheld. Study Design Retrospective cohort study. Setting Tertiary care hospital. Subjects and Methods Medical records of 414 adult patients undergoing anterior skull base procedures between January 1, 2014, and January 7, 2017, were retrospectively reviewed. Revision surgeries, skull base infections, sinus surgery, and orbital cases were excluded. Results Fifty-four (13.0%) patients with a diagnosis of OSA were identified. While the known patients with OSA were more likely to require postoperative supplemental oxygen (odds ratio [OR], 4.29; 95% confidence interval [CI], 2.38-7.75; P < .001), there was no increased risk of serious respiratory events or cerebrospinal fluid leak (CSF). To address the likely underdiagnosis of OSA in this cohort, subgroup analyses were performed of patients at high risk for OSA (body mass index >30 kg/m2 and hypertension) and demonstrated an increased risk of serious respiratory events (OR, 4.41; 95% CI, 1.24-15.7; P = .034) and CSF leak (13.6% vs 4.7%; P = .018). Conclusions Skull base patients with known OSA can be successfully managed with diligent care in the perioperative period when PAP therapy is withheld. However, OSA is likely underdiagnosed in the skull base population, and patients at high risk for undiagnosed OSA may be at the greatest risk for respiratory complications and CSF leak. Increased presurgical awareness and implementation of a perioperative management algorithm is needed.

Positive airway pressure adherence and mask interface in the setting of sinonasal symptoms.

OBJECTIVES/HYPOTHESIS: Despite reports of lower positive pressure adherence rates with oronasal masks, patients with sinonasal problems are often prescribed this interface over a nasal interface. The aim of this study was to characterize the relationship between mask type and therapy adherence in the setting of sinonasal symptoms. STUDY DESIGN: Retrospective case series with chart review. METHODS: We reviewed 328 patients who underwent positive pressure titration between January 2012 and May 2015. Follow-up adherence data were available for 218 patients (66.5%). Multivariate analysis examined whether patients with sinonasal symptoms have improved adherence with oronasal masks compared to nasal or nasal pillow interfaces. RESULTS: At a median follow-up of 95 days, positive pressure adherence in patients with sinonasal symptoms was highest with the nasal pillow interface. When compared with oronasal interfaces, the odds of adequate therapy adherence were >5 times greater with nasal pillow interfaces (odds ratio [OR] = 5.20, 95% confidence interval [CI] = 1.61-16.80, P = .006) and >3 times greater with nasal interfaces (OR = 3.67, 95% CI = 1.20-11.26, P = .02) in these symptomatic patients. CONCLUSIONS: The presence of nasal problems does not predict the need for an oronasal mask. Positive pressure adherence rates are higher with nasal and nasal pillow interfaces compared to oronasal masks, even in patients with sinonasal complaints. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2418-2422, 2017.

Audiometric Outcomes in Pediatric Temporal Bone Trauma.

OBJECTIVE: To characterize pediatric temporal bone trauma, focusing on audiometric outcomes. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care children's hospital. SUBJECTS AND METHODS: Cases were reviewed of children (<18 years) presenting over a 3-year period with computed tomography-proven temporal bone fracture and audiology examination. All scans were read by a neuroradiologist and reviewed by a pediatric otolaryngologist. Demographics, fracture pattern, and audiometric data were recorded. RESULTS: Fifty-eight patients (60 fractures) met inclusion criteria. The majority (93%) were otic capsule-sparing fractures. The types and severity of hearing loss were significantly different between the 2 fracture patterns. Based on pure-tone average, all otic capsule-violating fractures had abnormal initial audiograms; 75% of these losses were severe. Approximately half (54%) of otic capsule-sparing fractures had abnormal initial audiograms; a majority were mild losses (85%). All classifiable losses in otic capsule-violating cases were of mixed type, whereas the majority (75%) of losses in otic capsule-sparing cases were conductive. Regardless of classification, 72% of patients with otic capsule-sparing fractures and initially abnormal audiograms improved to normal levels at a mean of 48 days posttrauma; this increased to 83% when only conductive losses were considered. CONCLUSIONS: Hearing loss type and severity differ in otic capsule-sparing and otic capsule-violating temporal bone fractures. A majority of children with otic capsule-sparing fractures and associated hearing loss improve to normal levels in about 6 weeks, especially if the original loss is classified as solely conductive. Children who do not improve within this time frame may warrant early investigation into surgically correctable causes.

Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck.

We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30-58) months versus 52 (range: 13-84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC.

Suggested excisional margins for cutaneous malignant lesions based on Mohs micrographic surgery.

IMPORTANCE: Surgical excision of skin cancer is a common treatment, yet the proper surgical margin remains unclear. This study reviews data on lesions and their margins as defined by Mohs micrographic surgery. OBJECTIVE: To review margins as defined by Mohs micrographic surgery. DESIGN: Retrospective review of data from patients with skin cancer. SETTING: Academic medical center. PARTICIPANTS: All patients with nonmelanoma skin cancer. MAIN OUTCOME AND MEASURE: Size and final defect size were compared to calculate the margins needed. All lesions were categorized based on histologic characteristics. RESULTS: A total of 495 lesions were reviewed. All tumors and defects had precise measurements. The mean margins for low-risk basal cell carcinomas, high-risk basal cell carcinomas, low-risk squamous cell carcinomas, and high-risk squamous cell carcinomas were 2.4 mm, 3.7 mm, 2.6 mm, and 5.3 mm, respectively. Statistical differences in surgical margins were found between all low- and high-risk cancer types. Established high-risk zones (H-zone) for basal cell carcinoma and squamous cell carcinoma were not associated with larger margins. Margins required to excise completely 95% of all the low-risk basal cell carcinomas, high-risk basal cell carcinomas, low-risk squamous cell carcinomas, and high-risk squamous cell carcinomas, were 4.75 mm, 8 mm, 5 mm, and 13.25 mm, respectively. CONCLUSIONS AND RELEVANCE: Differences are noted between low- and high-risk cutaneous lesions. When primary excision instead of Mohs micrographic surgery is the only option, the aforementioned margins may be considered guidelines. The relevance of this study is to guide future management and margins for primary excision. LEVEL OF EVIDENCE: 3.

Refractory heparin induced thrombocytopenia with thrombosis (HITT) treated with therapeutic plasma exchange and rituximab as adjuvant therapy.

We report a case of refractory heparin-induced thrombocytopenia with thrombosis (HITT) with prolonged thrombocytopenia and multiple thrombotic complications that failed to improve despite aggressive treatment. A 60 year old female with a prior history of venous thromboembolism was admitted with an acute pulmonary embolism, and developed HITT after several days on heparin therapy. She suffered multiple complications including bilateral venous limb gangrene, acute renal failure, and refractory thrombocytopenia, leading us to use multimodality therapy including therapeutic plasma exchange (TPE) and rituximab immunosuppression. The patient had transient improvements in her thrombocytopenia with TPE, and rituximab was added in an attempt to reduce antibody production. She eventually required bilateral limb amputation, and only after removal of the gangrenous limbs did her platelet count show sustained improvement. We discuss the possible contribution of infection to her prolonged course.

Role of breast MRI in the preoperative evaluation of patients with newly diagnosed breast cancer.

OBJECTIVE: The purpose of our study was to evaluate in a non-investigational setting the effect of preoperative breast MRI on the diagnosis of unsuspected additional malignant tumors and on surgical management choices. SUBJECTS AND METHODS: One hundred ninety-nine patients with a new diagnosis of breast cancer who underwent preoperative bilateral breast MRI were enrolled. Data included additional imaging and biopsies performed, final surgical management, and pathologic correlation. To reduce bias due to patient preference and variable surgical approaches, ipsilateral malignant lesions found on breast MR images were retrospectively reviewed by a surgeon blinded to final surgical treatment. RESULTS: MRI detected additional suspicious previously unsuspected lesions in 74 patients (37%). Fifty-four of these lesions, in 38 patients (19%), were identified as malignant, of which 41 (76%) were invasive. Retrospective review of the MRI-identified ipsilateral malignant lesions resulted in hypothetical recommendations that would have altered the surgical treatment of 26 of the patients (13%), principally as mastectomy or wider excision. CONCLUSION: For patients with a new diagnosis of breast cancer, breast MRI in a mid-sized regional hospital depicts unsuspected malignant lesions in both the ipsilateral and contralateral breasts in proportions consistent with the results of earlier studies at larger institutions. Whether clinical outcome is improved by changes in surgical management consequent to MRI detection of unsuspected malignant lesions remains unproven.