Increased Peripheral Blood Neutrophil Activation Phenotypes and Neutrophil Extracellular Trap Formation in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series and Review of the Literature.

BACKGROUND: Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. METHODS: Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. RESULTS: Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1ß, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. CONCLUSIONS: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.

Delayed Facial Palsy After Resection of Vestibular Schwannoma: An Analysis of Long-term Facial Nerve Outcomes.

OBJECTIVES: 1) Identify clinical factors associated with delayed facial palsy (DFP) after microsurgical resection of vestibular schwannoma. 2) Determine whether DFP predicts worse facial nerve (FN) outcomes. METHODS: Adult patients (≥18 yrs) who underwent vestibular schwannoma resection between February 2008 and December 2017 were retrospectively reviewed. Postoperative House-Brackmann (HB) FN function was assessed on the day of surgery, daily during patients' inpatient admissions, and at postoperative clinic visits. Follow-up exceeded ≥12 months for all patients. DFP was defined as a decline (≥1 HB grade) in FN function (relative to the preoperative state) occurring between postoperative days 1 and 30. RESULTS: Two hundred ninety-one patients were analyzed. Mean age was 51.5 years (±12.3) and mean tumor size 20.6 mm (±10.8). Immediate FP occurred in 61 (21%) patients, and DFP occurred in 112 (38%) patients. Tumor size was largest in patients with immediate FP (p < 0.0001). On univariate analysis, DFP was associated with better final FN outcomes (OR 0.447, p = 0.0101) compared with immediate FP. Multivariate analysis, however, showed that timing of FP was no longer significant, whereas larger tumor size and preoperative HB2 function predicted worse FN outcomes (OR 2.718, p < 0.0001 and OR 9.196, p = 0.0039, respectively). In patients with DFP, longer time to onset of palsy predicted more favorable FN outcomes. CONCLUSIONS: When accounting for tumor size, the timing of onset of postoperative facial palsy does not predict final FN outcomes. In patients who develop DFP, the longer the interval between surgery and onset of weakness, the better the chances of good long-term FN function.

Preoperative Sudden Hearing Loss May Predict Hearing Preservation After Retrosigmoid Resection of Vestibular Schwannoma.

OBJECTIVES: Describe the effect of preoperative sudden hearing loss (SHL) on likelihood of hearing preservation (HP) after surgical resection of vestibular schwannoma (VS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adult patients (≥18 years) who underwent retrosigmoid VS resection for HP between February 2008 and December 2018 were reviewed. All patients had preoperative word recognition score (WRS) of at least 50%. Similarly, HP was defined as postoperative WRS of more than or equal to 50%. Regression analysis was used to describe the effect of SHL on HP, accounting for tumor size, and preoperative hearing quality. INTERVENTIONS: All patients underwent retrosigmoid VS resection for HP. MAIN OUTCOME MEASURES: WRS of at least 50%. RESULTS: Of 160 patients who underwent retrosigmoid VS resection during the study period, 153 met inclusion criteria. Mean tumor size was 14.0 (±6) mm. Hearing was preserved in 41.8% (n = 64). Forty patients (26.1%) had a history of preoperative SHL. Among 138 patients (90.2%) in whom the cochlear nerve was anatomically preserved during surgery, HP was achieved in 61.8% of those with SHL (21 of 34) and 41.3% of those without SHL (43 of 104) (p = 0.0480). On univariate and multivariate analysis (accounting for tumor size and preoperative hearing quality), SHL was a significant positive predictor of HP (odds ratio 2.292, p = 0.0407 and odds ratio 2.778, p = 0.0032, respectively). CONCLUSION: In patients with VS and retained serviceable hearing, SHL is an independent predictor of HP after retrosigmoid microsurgical resection when the cochlear nerve is preserved.

Predicting Long-Term Facial Nerve Outcomes After Resection of Vestibular Schwannoma.

OBJECTIVES: 1) Describe the effect of tumor size on facial nerve (FN) outcomes after microsurgical resection of vestibular schwannoma (VS).2) Describe the effect of surgical approach, preoperative radiation, and early postoperative facial function on long-term FN outcomes. STUDY DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Adult (≥18 yr) patients underwent translabyrinthine or retrosigmoid VS resection by a single neurotologist and single neurosurgeon between February 2008 and December 2017. MAIN OUTCOME MEASURES: Long-term FN outcomes (≥12 mo) according to House-Brackmann (HB) grade. RESULTS: During the study period, 350 patients underwent VS resection, of whom 290 met inclusion criteria. Translabyrinthine surgery was performed in 54% (n = 158) and retrosigmoid in 45% (n = 131). One patient underwent a combined approach. Among patients who underwent retrosigmoid approach, none had a tumor more than 30 mm. Gross total resection was achieved in 98% (n = 283). Long-term HB1-2 function was achieved in 90% (n = 261). On univariate analysis, tumor size (per cm increase), history of preoperative radiation, and worse HB score at discharge predicted worse FN function. Multivariate analysis showed that tumor size (per cm increase) and history of radiation were independent predictors of FN function. For patients with tumors less than 30 mm, multivariate analysis of tumor size and surgical approach was performed; tumor size remained predictive of worse FN function (odds ratio [OR] 2.362, p = 0.0035), whereas surgical approach was not significantly predictive (p = 0.7569). CONCLUSION: Tumor size and history of radiation predict long-term FN function after VS resection. When accounting for tumor size, the translabyrinthine and retrosigmoid approaches yield equivalent FN results.

The Effect of Tumor Size on Likelihood of Hearing Preservation After Retrosigmoid Vestibular Schwannoma Resection.

OBJECTIVES: 1) Describe the effect of tumor size on the likelihood of hearing preservation after retrosigmoid approach for resection of vestibular schwannoma (VS).2) Describe the effect of preoperative hearing status on the likelihood of hearing preservation. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adult (18 years or older) patients underwent retrosigmoid VS resection and postoperative audiometry between 2008 and 2018 and had a preoperative word recognition score (WRS) of at least 50%. Patients with a history of neurofibromatosis 2, radiation, or previous resection were excluded. INTERVENTIONS: All patients underwent retrosigmoid VS resection with attempted hearing preservation. MAIN OUTCOME MEASURES: WRS of at least 50%. RESULTS: Data from 153 patients were analyzed. Mean age was 50.8 (±11.3) years and mean tumor size 14 (±6) mm. Hearing was preserved and lost in 64 (41.8%) and 89 (58.2%) patients, respectively. Hearing preservation rates were higher for intrameatal tumors than for tumors with extrameatal extension (57.6% versus 29.4%, p = 0.0005). On univariate and multivariate regression analysis, tumor size (per mm increase) was a negative predictor of hearing preservation (odds ratio [OR] 0.893, p = 0.0002 and 0.841, p = 0.0005, respectively). Preoperative American Academy of Otolaryngology-Head & Neck Surgery Hearing Class was also predictive of hearing preservation (p = 0.0044). Class A hearing (compared with class B hearing) was the strongest positive risk factor for hearing preservation (OR 3.149, p = 0.0048 and 1.236, p = 0.0005, respectively). CONCLUSION: Small tumor size and preoperative class A hearing are positive predictors of hearing preservation in patients undergoing the retrosigmoid approach for VS resection.

Factors That Affect Length of Hospital Stay After Vestibular Schwannoma Surgery.

OBJECTIVE: To identify perioperative factors that influence hospital length of stay (LOS) after resection of vestibular schwannoma (VS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary skull base referral center. PATIENTS: Patients who underwent acoustic neuroma resection between January 1, 2007 and January 1, 2014. INTERVENTIONS: Approaches used for VS resection included translabyrinthine and retrosigmoid. MAIN OUTCOME MEASURES: LOS and several perioperative factors that may delay hospital discharge were examined. Factors included were patient demographics (age and sex), tumor characteristics (size), surgical factors (operative time, approach, revision surgery, date of surgery), and immediate postoperative factors (presence of vertigo or immediate postoperative complications). RESULTS: Two hundred eighty-eight patients underwent VS resection during the study period. Two hundred fifty-five patients had complete charts available for review. LOS ranged from 1 to 10 days with an average of 2.66 days and mode of 2 days. One hundred thirty-one patients were admitted for ≤2 days and 124 patients stayed longer. Of the perioperative factors examined with univariate analysis, female gender (p = 0.0266) and presence of postoperative vertigo (p < 0.0001) were statistically significant factors associated with LOS >2 days. On multivariate logistic regression analysis with odds ratios (OR), older patient age (OR = 1.028, p = 0.0177), female gender (OR = 1.810, p = 0.0314), longer operative time (OR = 1.424, p = 0.0007), and presence of postoperative vertigo (OR = 4.904, p < 0.0001) carried a statistically significant increased odds toward a LOS >2 days. CONCLUSIONS: VS surgery and postoperative care can be carried out efficiently with a minimal LOS. Identifying factors that may prolong LOS may help the operative team anticipate and address needs to optimize LOS.

Otolaryngology in Critical Care.

Diseases affecting the ear, nose, and throat are prevalent in intensive care settings and often require combined medical and surgical management. Upper airway occlusion can occur as a result of malignant tumor growth, allergic reactions, and bleeding events and may require close monitoring and interventions by intensivists, sometimes necessitating surgical management. With the increased prevalence of immunocompromised patients, aggressive infections of the head and neck likewise require prompt recognition and treatment. In addition, procedure-specific complications of major otolaryngologic procedures can be highly morbid, necessitating vigilant postoperative monitoring. For optimal outcomes, intensivists need a broad understanding of the pathophysiology and management of life-threatening otolaryngologic disease.

Treatment of OSA with CPAP Is Associated with Improvement in PTSD Symptoms among Veterans.

STUDY OBJECTIVES: Posttraumatic stress disorder (PTSD) is common among veterans of the military, with sleep disturbance as a hallmark manifestation. A growing body of research has suggested a link between obstructive sleep apnea and PTSD, potentially due to obstructive sleep apnea (OSA) related sleep disruption, or via other mechanisms. We examined the hypothesis that treatment of OSA with positive airway pressure would reduce PTSD symptoms over 6 months. METHODS: A prospective study of Veterans with confirmed PTSD and new diagnosis of OSA not yet using PAP therapy were recruited from a Veteran's Affairs sleep medicine clinic. All subjects were instructed to use PAP each night. Assessments were performed at 3 and 6 months. The primary outcome was a reduction in PTSD symptoms at 6 months. RESULTS: Fifty-nine subjects were enrolled; 32 remained in the study at 6 months. A significant reduction in PTSD symptoms, measured by PCL-S score was observed over the course of the study (60.6 ± 2.7 versus 52.3 ± 3.2 points; p < 0.001). Improvement was also seen in measures of sleepiness, sleep quality, and daytime functioning, as well as depression and quality of life. Percentage of nights in which PAP was used, but not mean hours used per night, was predictive of improvement. CONCLUSIONS: Treatment of OSA with PAP therapy is associated with improvement in PTSD symptoms, although the mechanism is unclear. Nonetheless, PAP should be considered an important component of PTSD treatment for those with concurrent OSA. Improving PAP compliance is a challenge in this patient population warranting further investigation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02019914. COMMENTARY: A commentary on this article appears in this issue on page 5.

Primary treatment of idiopathic sudden sensorineural hearing loss with intratympanic dexamethasone.

PURPOSE OF REVIEW: Systemic corticosteroids have been the mainstay of treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) for over 30 years. Recently, intratympanic steroids have risen in popularity; however, there is no consensus regarding the details of their application. The purpose of this article is to review the current literature and share our opinion that intratympanic dexamethasone (alone or with systemic steroids) should be offered as primary treatment of ISSNHL. RECENT FINDINGS: Intratympanic steroids have been shown to result in higher inner ear concentrations than systemic steroids in animal and human studies. Primary treatment of ISSNHL with intratympanic steroids in combination with systemic steroids has been demonstrated to result in better hearing outcomes than systemic steroids alone. Recent evidence has revealed these hearing outcomes to be dependent on the dose of intratympanic steroid. Dexamethasone may be better absorbed than methylprednisolone, and potentially offer a greater benefit. Furthermore, intratympanic steroids provide an effective alternative for patients who cannot tolerate systemic steroids. SUMMARY: Intratympanic dexamethasone alone, or in combination with systemic steroids, provides effective treatment of ISSNHL and should be utilized as primary treatment. Further investigation is required to determine the optimal choice, concentration, and administration schedule of intratympanic steroids.

Dose Effect of Intratympanic Dexamethasone for Idiopathic Sudden Sensorineural Hearing Loss: 24 mg/mL Is Superior to 10 mg/mL.

OBJECTIVE: To compare outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL) treated with intratympanic (IT) dexamethasone (DEX) at either 10 mg/mL or 24 mg/mL. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Thirty-seven adults with ISSNHL. INTERVENTIONS: In addition to concurrent prednisone taper, patients received a series of IT DEX injections for 2 weeks with either 10 mg/mL or 24 mg/mL. MAIN OUTCOME MEASURE: Greater than 30-dB improvement in pure-tone average (PTA). RESULTS: Baseline characteristics were similar between groups. Mean follow-up was 10 weeks. Ten (53%) of 19 patients treated with 24 mg/mL had greater than 30-dB improvement in PTA compared with 3 (17%) of 18 treated with 10 mg/mL (p = 0.0382, Fisher's exact test). There was a trend toward improved word recognition score outcome with 24 mg/mL. The interval between onset and initiation of IT DEX significantly affected outcome, with earlier treatment resulting in greater improvement in PTA and word recognition score. Multivariate logistic regression confirmed that IT DEX dose and interval to starting treatment were both independent predictors of PTA outcome. Change in PTA was not significantly affected by age, sex, pretreatment hearing levels, or concurrent treatment with hyperbaric oxygen. CONCLUSION: To our knowledge, this is the first demonstration of superiority of IT DEX at 24 mg/mL for the treatment of ISSNHL, with significantly better recovery of PTA. Our data suggest that treatment should be initiated as soon as possible. A prospective randomized trial to confirm the optimal dose is warranted.

Hearing preservation and vestibular schwannoma: intracochlear FLAIR signal relates to hearing level.

OBJECTIVES: This study aimed to evaluate the relationship between cochlear signal on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences and hearing in patients undergoing hearing preservation surgery for vestibular schwannoma (VS) and to demonstrate a new classification system to be used in imaging evaluation of patients with VS. METHODS: A search of archived surgical cases at a single institution between January 1, 2006, and January 1, 2012, revealed 51 patients who underwent hearing preservation surgery for VS. Tumor size, patient age and sex, and preoperative and postoperative pure-tone average (PTA) and speech discrimination score (SDS) were recorded. Cochleae on the affected side were examined on preoperative FLAIR sequences and classified as limited hyperintensity (LH) or extensive hyperintensity (EH). RESULTS: Mean patient age was 51 years, and mean tumor size was 1.3 cm. Preoperative FLAIR sequences were classified into LH (n = 36) and EH (n = 15) categories. Preoperative PTA and SDS were 29.5 dB (SD, 16.7), 90% (SD, 14) and 40.6 dB (SD, 13.8), 80% (SD, 25) for LH and EH, respectively. On univariate analysis, preoperative PTA was superior in the LH group (p = 0.04). There was a trend toward superior preoperative SDS and postoperative PTA in the LH group, but these differences were not statistically significant (p = 0.08 and p = 0.06, respectively). CONCLUSION: The current study is the first to demonstrate a distinct association between cochlear FLAIR signal and pretreatment hearing levels in patients with VS. A new classification system for evaluating cochlear FLAIR signal is proposed. Improvement in FLAIR sequences will allow further investigation of this association.

Incidence of sudden sensorineural hearing loss.

OBJECTIVE: Recent data regarding the incidence of sudden sensorineural hearing loss (SSNHL) in the United States is lacking. The objective of this study was to assess the current day incidence of SSNHL in the United States using data from a medical and pharmaceutical claims database containing information for more than 60 million unique patients. STUDY DESIGN: Population-based cross-sectional analysis. SETTING: Inpatient and outpatient. PATIENTS: Patients in the database are reported to be representative of the national, commercially insured population on a variety of demographic measures including age, sex, health plan type, and geographic location. RESULTS: During 2006 and 2007, the annual incidence of SSNHL was 27 per 100,000 in the United States. The incidence increased with increasing age, ranging from 11 per 100,000 for patients younger than 18 years to 77 per 100,000 for patients 65 years and older. There was an overall slight male preponderance with a male-to-female ratio of 1.07:1. This was more pronounced in patients 65 years and older, with a ratio of 1.30:1. CONCLUSION: More than 66,000 new cases of SSNHL are seen annually in the United States. The disorder is more common in men and the elderly.

Current epidemiology of Meniere's syndrome.

The burden of Ménière syndrome (MS) is substantial, especially when considering the significant impact on the quality of life of those affected. Reported estimates of incidence and prevalence have varied widely due to methodological differences between studies, changes in criteria for diagnosis of MS, and differences in populations studied. Reported prevalence rates for MS range from 3.5 per 100,000 to 513 per 100,000. A recent study using health claims data for more than 60 million patients in the United States found prevalence of 190 per 100,000 with a female:male ratio of 1.89:1. The prevalence of MS increases with increasing age.

Pulmonary langerhans cell histiocytosis diagnosed in a cervical lymph node: a case report.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is usually confined to the lungs and is therefore an unexpected finding in a cervical lymph node. CASE: A 52-year-old male with a 40-pack-year smoking history presented to our clinic with cough, fever and cervical lymphadenopathy. Chest computed tomography (CT) showed bilateral pulmonary nodules and enlarged mediastinal lymph nodes, worrisome for an infectious or malignant process. Bronchioloalveolar lavage was nondiagnostic. Fine needle aspiration cytology of the enlarged cervical lymph node revealed atypical histiocytoid cells, suspicious for malignancy. Immunohistochemistry revealed CD1a- and S-100-positive Langerhans cells. These findings, along with the patient's extensive smoking history and characteristic radiographic nodules, favored a diagnosis of PLCH with cervical lymph node involvement. The patient was advised to cease smoking, and no therapy was administered. Months later, follow-up chest CT showed spontaneous resolution of the lung nodules. CONCLUSION: The demonstration of Langerhans cells by immunohistochemical staining of CD1a and S-100 on a fine needle aspiration cell block is a useful diagnostic adjunct. In this case, definitive cytology for Langerhans cells in the appropriate clinical and radiologic setting allowed us to arrive at the correct diagnosis of PLCH in a minimally invasive manner.

Insulin-like growth factor-I and growth differentiation factor-5 promote the formation of tissue-engineered human nasal septal cartilage.

INTRODUCTION: Tissue engineering of human nasal septal chondrocytes offers the potential to create large quantities of autologous material for use in reconstructive surgery of the head and neck. Culture with recombinant human growth factors may improve the biochemical and biomechanical properties of engineered tissue. The objectives of this study were to (1) perform a high-throughput screen to assess multiple combinations of growth factors and (2) perform more detailed testing of candidates identified in part I. METHODS: In part I, human nasal septal chondrocytes from three donors were expanded in monolayer with pooled human serum (HS). Cells were then embedded in alginate beads for 2 weeks of culture in medium supplemented with 2% or 10% HS and 1 of 90 different growth factor combinations. Combinations of insulin-like growth factor-I (IGF-1), bone morphogenetic protein (BMP)-2, BMP-7, BMP-13, growth differentiation factor-5 (GDF-5), transforming growth factor ß (TGFß)-2, insulin, and dexamethasone were evaluated. Glycosaminoglycan (GAG) accumulation was measured. A combination of IGF-1 and GDF-5 was selected for further testing based on the results of part I. Chondrocytes from four donors underwent expansion followed by three-dimensional alginate culture for 2 weeks in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5. Chondrocytes and their associated matrix were then recovered and cultured for 4 weeks in 12 mm transwells in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5 (the same medium used for alginate culture). Biochemical and biomechanical properties of the neocartilage were measured. RESULTS: In part I, GAG accumulation was highest for growth factor combinations including both IGF-1 and GDF-5. In part II, the addition of IGF-1 and GDF-5 to 2% HS resulted in a 12-fold increase in construct thickness compared with 2% HS alone (p < 0.0001). GAG and type II collagen accumulation was significantly higher with IGF-1 and GDF-5. Confined compression modulus was greatest with 2% HS, IGF-1, and GDF-5. CONCLUSION: Supplementation of medium with IGF-1 and GDF-5 during creation of neocartilage constructs results in increased accumulation of GAG and type II collagen and improved biomechanical properties compared with constructs created without the growth factors.

Current-day prevalence of Ménière's syndrome.

Previously reported prevalence rates of Ménière's syndrome (MS) have ranged from 3.5 per 100000 to 513 per 100000. Recent data regarding the prevalence in the United States are lacking. To further assess the current-day prevalence of MS in the US, data from a medical and pharmaceutical claims database containing information for over 60 million unique patients were analyzed. Patients in the database are representative of the national, commercially insured population on a variety of demographic measures including age, gender, health plan type, and geographic location. A 3-year period from 2005 to 2007 was analyzed. The prevalence of MS was 190 per 100000 with a female:male ratio of 1.89:1. The prevalence increased with increasing age, ranging from 9 per 100000 for patients under age 18 to 440 per 100000 for patients 65 years and older.