HIV envelope protein gp120-induced apoptosis in lung microvascular endothelial cells by concerted upregulation of EMAP II and its receptor, CXCR3.

Chronic lung diseases, such as pulmonary emphysema, are increasingly recognized complications of infection with the human immunodeficiency virus (HIV). Emphysema in HIV may occur independent of cigarette smoking, via mechanisms that are poorly understood but may involve lung endothelial cell apoptosis induced by the HIV envelope protein gp120. Recently, we have demonstrated that lung endothelial apoptosis is an important contributor to the development of experimental emphysema, via upregulation of the proinflammatory cytokine endothelial monocyte-activating polypeptide II (EMAP II) in the lung. Here we investigated the role of EMAP II and its receptor, CXCR3, in gp120-induced lung endothelial cell apoptosis. We could demonstrate that gp120 induces a rapid and robust increase in cell surface expression of EMAP II and its receptor CXCR3. This surface expression occurred via a mechanism involving gp120 signaling through its CXCR4 receptor and p38 MAPK activation. Both EMAP II and CXCR3 were essentially required for gp120-induced apoptosis and exposures to low gp120 concentrations enhanced the susceptibility of endothelial cells to undergo apoptosis when exposed to soluble cigarette smoke extract. These data indicate a novel mechanism by which HIV infection causes endothelial cell loss involved in lung emphysema formation, independent but potentially synergistic with smoking, and suggest therapeutic targets for emphysema prevention and/or treatment.

Characteristics of Facial Trauma in Professional Mixed Martial Arts.

Background: Injuries are common in mixed martial arts (MMA) competitions. However, the risk factors for facial injury have not been delineated. Objective: Identify the facial injuries and associated risk factors of professional MMA fights. Methods: The Nevada State Athletic Commission medical injury reports from all professional Ultimate Fighting Championship bouts from 2010 to 2020 was reviewed. Fighter characteristics, details of the competition, and injuries sustained were collected. Binary logistic regressions determined significant predictors of facial injury. Results: A total of 1462 fighters were included. Most participants were male (91.0%) with mean age of 29.5 ± 4.1 years. Most fights took place between 135 and 185 lbs., lasted ≥3 rounds (59.4%), and resulted in judges' decision (50.5%) or knockout (31.2%). The facial injury rate was 15.8%, which were predominantly lacerations (12.0%) and fractures (3.6%). Multivariate regression revealed being male (p = 0.026), heavier weight (p = 0.028), more rounds fought (p = 0.019), losing (p < 0.001), and nonsubmission outcome (p = 0.017) predicted facial injury. Conclusion: Facial injuries are common in MMA fighting. The risks should be iterated to participants in this sport.

Treatment of post-tonsillectomy hemorrhage with nebulized tranexamic acid: A retrospective study.

OBJECTIVE: To evaluate the association of treatment with nebulized tranexamic acid (TXA) with rates of operative intervention in post-tonsillectomy hemorrhage (PTH). METHODS: Single tertiary-referral center and satellite hospitals, retrospective cohort of adult and pediatric patients who were diagnosed with PTH in 2015-2022 and treated with nebulized TXA and standard care, compared with an age- and gender-matched control cohort treated with standard care. Patients were typically treated in the emergency department with a single dose of 500mg/5 mL TXA delivered via nebulizer. RESULTS: 1110 total cases of PTH were observed, and 83 were treated with nebulized TXA. Compared to 249 age- and gender-matched PTH controls, TXA-treated patients had a rate of operating room (OR) intervention of 36.1% versus 60.2% (p < 0.0001) and a rate of repeat bleeding of 4.9% versus 14.2% (p < 0.02). The odds ratio for OR intervention with TXA treatment was 0.37 (95% CI 0.22, 0.63). There were no adverse effects identified with an average follow-up time of 586 days. CONCLUSION: Treatment of PTH with nebulized TXA is associated with lower rates of operative intervention and lower rates of repeat bleeding events. Prospective studies are needed to further characterize efficacy and optimal treatment protocols.

Inflammatory Reactions to Laryngeal Injection of Hyaluronic Acid Derivatives.

OBJECTIVES/HYPOTHESIS: To report the rate and describe the characteristics and management of inflammatory reactions following injection laryngoplasty with hyaluronic acid derivatives. STUDY DESIGN: Single institution, retrospective review. METHODS: Adult and pediatric patients who underwent injection laryngoplasty with hyaluronic acid derivatives from 2013 to 2020 were identified. Demographics, indication for injection, type and volume of injected material, and use of general anesthesia were obtained. When a postoperative inflammatory response occurred, information regarding clinical presentation, timing, and subsequent management was collected. RESULTS: A total of 464 patients who underwent 536 laryngeal injections with hyaluronic acid derivatives were included. There were 365 adult patients (median age 62 years) who underwent 431 injections and 99 pediatric patients (median age 2 years) who underwent 105 injections. The most common indications for injection were abnormal vocal fold mobility (70.3%) and aspiration (83.8%) for adult and pediatric patients, respectively. Juvéderm® was used in 449 cases (79.8% adult, 100% pediatric), and Restylane® was used in the remaining adult cases (20.2%). Procedures were mostly performed under general anesthesia (67.7% adult, 100% pediatric) with median injection volumes of 0.6 mL for adult and 0.3 mL for pediatric patients. An inflammatory reaction occurred following 3 of 536 injections (0.6%), all utilizing Juvéderm®. All three patients presented with stridor, dyspnea, and laryngeal edema within two days of injection. Each patient was admitted for observation and successfully treated with intravenous steroids and inhaled racemic epinephrine. One patient with comorbid pneumonia was intubated and required concomitant treatment with broad-spectrum antibiotics. CONCLUSIONS: Inflammatory reactions to hyaluronic acid derivatives used in injection laryngoplasty are rare but represent significant patient morbidity and can be managed with anti-inflammatory and airway stabilizing measures. Patients should be counseled appropriately regarding the risks of injection laryngoplasty with hyaluronic acid derivatives.

Indiscriminate Pathologic Examination of Pediatric Supraglottoplasty Specimens: An Evidence-Based Approach toward Exempt Status.

OBJECTIVE: The primary aim of this study was to demonstrate that indiscriminate pathologic evaluation of supraglottoplasty specimens is unnecessary and does not influence postoperative management. The secondary objective was to determine the costs associated with pathologic evaluation of supraglottoplasty specimens. METHODS: A planned chart review was conducted to evaluate data from consecutive patients undergoing supraglottoplasty. Demographic data were extracted and pathology reports were reviewed. Projected cost savings were estimated based on 2018 Centers for Medicare & Medicaid Services reimbursement rates for Current Procedural Terminology code 88304 (surgical pathology, gross and microscopic examination). RESULTS: A total of 1417 consecutive patients were identified. All specimens underwent gross and microscopic examination. Pathologic outcomes were categorized into 3 major categories: no diagnostic abnormality (n = 1069), chronic inflammation (n = 346), and other (n = 2). Pathologic evaluation did not alter postoperative management in any patient. Projected yearly and 5-year cost- savings totaled $11,818.08 and $59,173.92, respectively. DISCUSSION: These findings demonstrate that pathologic examination of supraglottoplasty specimens adds no value to patient management. A more selective approach to pathologic examination of certain surgical specimens is an improvement opportunity to enhance the value of patient care by eliminating direct financial costs and "hidden costs" associated with unnecessarily increased workload. IMPLICATIONS FOR PRACTICE: Addressing inappropriate, indiscriminate pathologic examination of certain surgical specimens is a potential quality improvement opportunity that has a meaningful impact on the value of patient care and reduces strains on the workload of surgical and pathology department personnel.

Manifestations of Pediatric Extranodal Rosai Dorfman Disease in the head and neck.

OBJECTIVES: To systematically evaluate the clinico-diagnostic profile and management outcomes of otorhinolaryngologic manifestations of Extranodal Rosai-Dorfman Disease (ENRDD) in the pediatric population. METHODS: The search terms Rosai Dorfman Disease and Sinus Histiocytosis were used to query PubMed, Ovid/Medline, and Scopus databases from inception through September 30, 2018. Studies were systematically reviewed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. All reports of ENRDD involving at least one otorhinolaryngologic subsite in children less than 18 years were eligible for inclusion. RESULTS: A total of 31 studies met inclusion criteria resulting in identification of 31 ENRDD cases with a mean age of 11.5 years. Of the 31 patients, 23 were male (74.2%) and 7 were female (22.6%). Extranodal lesions were limited to otorhinolaryngologic subsites in 24 patients (77.4%), while 7 patients (22.5%) were found to have extranodal lesions simultaneously involving otorhinolaryngologic and nonotorhinolaryngologic sites. The nasal vault was the most common otorhinolaryngologic site involved (n = 13, 41.9%), followed by the paranasal sinuses (n = 10, 32.3%). The most common non-otorhinolaryngologic site that was concurrently involved was the orbit (n = 4, 57.1%). Concurrent cervical lymphadenopathy was present in 19 patients (61.2%). While not documented for 2 cases, emperipolesis on histopathology was confirmed in 29 patients (93.5%). Single therapy with surgical excision was the most common modality of treatment (n = 15, 53.6%) and yielded highest remission rates (80%). In 11 instances (34.36%), ENRDD was misdiagnosed. CONCLUSION: Pediatric ENRDD is a rare disease entity that maintains a high misdiagnosis potential. The most common otorhinolaryngologic location for extranodal manifestation is the sinonasal compartment. Surgical excision remains the most common treatment modality yielding lowest persistence and/or recurrence rates.

Immunosuppression Impact on Head and Neck Cutaneous Squamous Cell Carcinoma: A Systematic Review with Meta-analysis.

OBJECTIVE: The primary objective was to define and quantify the relationship between immunosuppression and prognosis in patients with cutaneous squamous cell carcinoma of the head and neck. DATA SOURCES: Ovid/Medline, PubMed, Embase, and Scopus were searched from inception through June 5, 2017, with cross-referenced subject headings of squamous cell carcinoma, skin neoplasms, head and neck neoplasms, and prognosis. Additional gray literature was queried. REVIEW METHODS: All prospective, retrospective, and cohort studies in the English literature investigating prognosis in patients with head and neck cutaneous squamous cell carcinoma were eligible for inclusion. Meta-analysis data were pooled using the fixed-effects model. The main outcome measures were hazard ratios detailing subgroup analysis between immunosuppressed and immunocompetent patients. RESULTS: Seventeen studies were eligible for inclusion; 317 of the 2886 patients were immunosuppressed. Meta-analysis with pooled hazard ratios was performed for all outcome variables with at least 3 reported hazard ratios. Immunosuppression portended a worse prognosis across all outcome variables of interest: locoregional recurrence (2.20; 95% confidence interval [CI], 1.45-3.36), disease-free survival (2.69; 95% CI, 1.60-4.51), disease-specific survival (3.61; 95% CI, 2.63-4.95), and overall survival (2.09; 95% CI, 1.64-2.67). CONCLUSION: This is the largest investigation into the impact of immunosuppression on head and neck cutaneous squamous cell carcinoma. Immunosuppressed patients experience worse recurrence and survival outcomes compared to immunocompetent counterparts. The data support formal inclusion of immunosuppression in head and neck cutaneous squamous cell carcinoma staging systems.

Sinonasal Chondromyxoid Fibroma: Case Report and Literature Review.

Chondromyxoid fibroma (CMF) is a rare, benign neoplasm of the chondroid, myxoid, and fibrous tissue. It characteristically affects the lower extremity long bones, although it may rarely arise within the craniofacial skeleton. We report the diagnosis and management of a 31-year-old male with a large, incidentally discovered CMF originating from the sphenoid sinus. A subsequent review of the literature reveals the need to differentiate from more aggressive neoplasms, such as chondrosarcoma and chondroma, which share radiographic features. A histopathologic examination is crucial for proper diagnosis and treatment. We discuss clinical sequelae, highlight the importance of a thorough pre-operative evaluation, and summarize previously suggested treatment paradigms.

Aspiration of Aluminum Beverage Can Tab: Case Report and Literature Review.

We describe the case of a 16-year-old male who aspirated a beverage can tab resulting in significant functional impairment. Since the introduction of beverage can opening tabs ("pop-tops" or "pull-tabs") nearly 50 years ago, five cases of their aspiration have been reported in the literature and this is the first case to report tracheal lodgment. We describe the clinical course for this patient including the inadequacy of radiographic evaluation and a significant delay in diagnosis. We highlight unique features of small aluminum foreign bodies that require consideration and mention a potential change in epidemiology associated with evolving product design. Our primary objective is increased awareness among otolaryngologists that radiography is unreliable for diagnosis or localization of small aluminum foreign bodies. The patient history must therefore be incorporated with other imaging modalities and/or endoscopic evaluation. Also, given the marked prevalence of aluminum beverage cans, we suspect that the inadvertent aspiration of can tabs is more common than indicated by the paucity of published reports.

Diagnostic Delays and Errors in Head and Neck Cancer Patients: Opportunities for Improvement.

A retrospective review of 100 sequential patients (2009-2012) with head and neck cancer was performed to determine the frequency of 5 types of diagnostic delays and errors outlined by the Institute of Medicine. There were a total of 105 diagnostic delays/errors. The most common was delay in being seen in the otolaryngology clinic after referral placement (28.6%), followed by diagnostic error by the referring physician (22%), delay in referral of a symptomatic patient to the otolaryngology clinic (16.2%), delay in employing an appropriate diagnostic test or procedure (15.2%), delay in action following reporting of pathology or imaging results for an incidental lesion (11.4%), diagnostic error by the otolaryngology clinic (2.8%), delay in action following reporting of pathology or imaging results for the symptomatic lesion (2.8%), and use of outmoded tests or therapy (1%). Increased awareness of these types of delays/errors will direct actions and processes to reduce or eliminate them.

Harnessing the Endocannabinoid 2-Arachidonoylglycerol to Lower Intraocular Pressure in a Murine Model.

PURPOSE: Cannabinoids, such as Δ9-THC, act through an endogenous signaling system in the vertebrate eye that reduces IOP via CB1 receptors. Endogenous cannabinoid (eCB) ligand, 2-arachidonoyl glycerol (2-AG), likewise activates CB1 and is metabolized by monoacylglycerol lipase (MAGL). We investigated ocular 2-AG and its regulation by MAGL and the therapeutic potential of harnessing eCBs to lower IOP. METHODS: We tested the effect of topical application of 2-AG and MAGL blockers in normotensive mice and examined changes in eCB-related lipid species in the eyes and spinal cord of MAGL knockout (MAGL-/-) mice using high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). We also examined the protein distribution of MAGL in the mouse anterior chamber. RESULTS: 2-Arachidonoyl glycerol reliably lowered IOP in a CB1- and concentration-dependent manner. Monoacylglycerol lipase is expressed prominently in nonpigmented ciliary epithelium. The MAGL blocker KML29, but not JZL184, lowered IOP. The ability of CB1 to lower IOP is not desensitized in MAGL-/- mice. Ocular monoacylglycerols, including 2-AG, are elevated in MAGL-/- mice but, in contrast to the spinal cord, arachidonic acid and prostaglandins are not changed. CONCLUSIONS: Our data confirm a central role for MAGL in metabolism of ocular 2-AG and related lipid species, and that endogenous 2-AG can be harnessed to reduce IOP. The MAGL blocker KML29 has promise as a therapeutic agent, while JZL184 may have difficulty crossing the cornea. These data, combined with the relative specificity of MAGL for ocular monoacylglycerols and the lack of desensitization in MAGL-/- mice, suggest that the development of an optimized MAGL blocker offers therapeutic potential for treatment of elevated IOP.

Unilateral Cervical Polyneuropathies following Concurrent Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer.

We report a constellation of cervical polyneuropathies in a patient treated with concurrent bortezomib, cetuximab, and cisplatin alongside intensity modulated radiotherapy for carcinoma of the tonsil with neck metastasis. The described deficits include brachial plexopathy, cervical sensory neuropathy, and oculosympathetic, recurrent laryngeal, and phrenic nerve palsies within the ipsilateral radiation field. Radiation neuropathy involving the brachial plexus is typically associated with treatment of breast or lung cancer; however, increased awareness of this entity in the context of investigational agents with potential neuropathic effects in head and neck cancer has recently emerged. With this report, we highlight radiation neuropathy in the setting of investigational therapy for head and neck cancer, particularly since these sequelae may present years after therapy and entail significant and often irreversible morbidity.

Lean Belt Certification: Pathway for Student, Resident, and Faculty Development and Scholarship.

Since July 2013, 20 trainee participants have completed the quality improvement curriculum within the Indiana University Department of Otolaryngology-Head & Neck Surgery, including 7 otolaryngology residents, 6 otolaryngology-bound medical students, and 7 psychiatry residents. Nine faculty and staff attended. Participants were highly satisfied with the quality and effectiveness of the program. Following program implementation, 2 otolaryngology residents and 2 medical students initiated their own quality improvement projects. Lean training directly resulted in oral and poster presentations at national conferences, journal publications, and institutional research and quality awards. Students completing the program established a local affiliate group of an international health care quality organization. Quality improvement training can be successfully incorporated into residency training with overwhelming program satisfaction and results in greater scholarly and professional development for motivated participants. The skillset acquired by participants leads to projects that improve patient care, increase value, and justify equipment and personnel retention and expansion.

Impact of Lean on surgical instrument reduction: Less is more.

OBJECTIVES/HYPOTHESIS: To determine whether instrument sets that are frequently used by multiple surgeons can be substantially reduced in size with consensus. STUDY DESIGN: Prospective quality improvement study using Lean Six Sigma for purposeful and consensual reduction of non-value-added instruments in adenotonsillectomy instrument sets. METHODS: Value stream mapping was utilized to determine instrumentation usage and reprocessing workflow. Preintervention instrument utilization surveys allowed consensual and intelligent set reduction. Non-value-added instruments were targeted for waste elimination by placement in a supplemental set. Times for pre- and postintervention instrument assembly, Mayo setup, and surgery were collected for adenotonsillectomies. Postintervention satisfaction surveys of surgeons and staff were conducted. RESULTS: Adenotonsillectomy sets were reduced from 52 to 24 instruments. Median assembly times were significantly reduced from 8.4 to 4.7 minutes (P < .0001) with a set assembly cost reduction of 44%. Following natural log transformations, mean Mayo setup times were significantly reduced from 97.6 to 76.1 seconds (P < .0001), and mean operative times were not significantly affected (1,773 vs. 1,631 seconds, P > .05). The supplemental set was opened in only 3.6% of cases. Satisfaction was >90% regarding the intervention. Set build cost was reduced by $1,468.99 per set. CONCLUSIONS: Lean Six Sigma improves efficiency and reduces waste by empowering team members to improve their environment. Instrument set reduction is ideal for waste elimination because of tool accumulation over time and instrument obsolescence as newer technologies are adopted. Similar interventions could easily be applied to larger sinus, mastoidectomy, and spine sets. LEVEL OF EVIDENCE: NA.

Sex Differences and the Impact of Chronic Stress and Recovery on Instrumental Learning.

We have previously shown that 21-day chronic restraint stress impacts instrumental learning, but overall few studies have examined sex differences on the impact of stress on learning. We further examined sex differences in response to extended 42-day chronic stress on instrumental learning, as well as recovery from chronic stress. Rats were tested in aversive training tasks with or without prior appetitive experience, and daily body weight data was collected as an index of stress. Relative to control animals, reduced body weight was maintained from day 22 through day 42 across the stress period for males, but not for females. Stressed males had increased response speed and lower learning efficiency during appetitive acquisition and aversive learning. Males overall showed slower escape shaping times and more shock exposure. In contrast, stressed females showed slower appetitive response speeds and higher appetitive and aversive efficiency but overall reduced avoidance rates during acquisition and maintenance for transfer animals and during maintenance for aversive-only animals. These tasks reveal important nuances on the effect of stress on goal-directed behavior and further highlight sexually divergent effects on appetitive versus aversive motivation. Furthermore, these data underscore that systems are temporally impacted by chronic stress in a sexually divergent pattern.