Predictive capacity of immune-related adverse events and cytokine profiling in neoadjuvant immune checkpoint inhibitor trials for head and neck squamous cell carcinoma.

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status. METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival were compared. Canonical linear discriminant analysis (LDA) was performed to identify combinations of circulating cytokines predictive of irAEs using plasma sample multiplex assay. RESULTS: Of 113 participants meeting inclusion criteria, 32 (28.3%) developed irAEs during treatment or follow-up. Positive p16 status was associated with irAEs (odds ratio [OR] 2.489; 95% CI 1.069-6.119; p = 0.043). irAEs were associated with pathologic treatment response (OR 3.73; 95% CI 1.34-10.35; p = 0.011) and with higher OS in the combined cohort (HR 0.319; 95% CI 0.113-0.906; p = 0.032). Patients with irAEs within the nivolumab cohort had significant elevations of select cytokines pre-treatment. Canonical LDA identified key drivers of irAEs among all trials, which were highly predictive of future irAE status. CONCLUSIONS: irAEs are associated with response to neoadjuvant ICI therapy in HNSCC and can serve as clinical indicators for improved clinical outcomes. irAEs can be predicted by concentrations of several circulating cytokines prior to treatment.

Device-related outcomes following hypoglossal nerve stimulator implantation.

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HGNS) has been widely used to treat obstructive sleep apnea in selected patients. Here we evaluate rates of revision and explant related to HGNS implantation and assess types of adverse events contributing to revision and explant. METHODS: Post-market surveillance data for HGNS implanted between January 1, 2018 and March 31, 2022, were collected. Event rates and risk were calculated using the post-market surveillance event counts and sales volume over the same period. Indications were categorized for analysis. Descriptive statistics were reported and freedom from explant or revision curves were grouped by year of implantation. RESULTS: Of the 20,881 HGNS implants assessed, rates of explant and revision within the first year were 0.723% and 1.542%, respectively. The most common indication for explant was infection (0.378%) and for revision was surgical correction (0.680%). Of the 5,820 devices with three-year post-implantation data, the rate of explant was 2.680% and of revision was 3.557%. During this same interval, elective removal (1.478%) was the most common indication, and for revisions, surgical correction (1.134%). CONCLUSIONS: The efficacy of HGNS is comparable in the real world setting to published clinical trial data. Rates of explant and revision are low, supporting a satisfactory safety profile for this technology.

Long-Term Outcomes in Patients With Trisomy 21 and Obstructive Sleep Apnea.

OBJECTIVE: To better understand the long-term health implications of obstructive sleep apnea (OSA) on patients with Trisomy 21 (T21) and the role of sleep surgery as a therapeutic intervention. STUDY DESIGN: Retrospective large database review. SETTING: The prevalence of OSA is as high as 75% in patients with T21. We sought to examine the cardiovascular, neurological, and endocrinological outcomes of patients with T21 10 years after their diagnosis of OSA. METHODS: TriNetX, an electronic medical record database, was queried for health outcomes in patients with T21 after diagnosis of OSA. The group was further analyzed to identify those who underwent sleep surgery, including hypoglossal nerve stimulation, palatopharyngoplasty, or adenotonsillectomy. RESULTS: Ten years after diagnosis, patients with OSA and T21 had a significantly higher incidence of death, myocardial infarction, cerebral infarction, heart failure, cardiac arrhythmia, ischemic heart disease, atrial fibrillation, essential hypertension, pulmonary hypertension, diabetes mellitus, and Alzheimer's disease compared to patients with T21 alone. Patients with OSA and T21 who underwent sleep surgery had significantly reduced incidence of adverse health outcomes compared to patients using continuous positive airway pressure. CONCLUSION: Our findings suggest that patients with T21 and OSA are at higher risk of poor health outcomes, which may require closer monitoring for earlier diagnosis and management of comorbid conditions. Sleep surgery is a suitable treatment modality for mitigating the risk of adverse outcomes in this population and should be considered in patients who are eligible surgical candidates.

Current Pediatric Tertiary Care Practices Following Adenotonsillectomy: An Update.

OBJECTIVE: Adenotonsillectomy is a common procedure performed in children, and the practice patterns at academic centers have been evolving with the publication of updated societal guidelines. In this study, we assess perioperative practice patterns at tertiary care children's hospitals for children undergoing adenotonsillectomy. METHODS: A cross-sectional 18-question survey distributed in July of 2022 recruited responses through August 25, 2022. The division chiefs of 70 pediatric otolaryngology groups at tertiary care children's hospitals across the United States and Canada were surveyed. Division chiefs submitted survey responses on behalf of the group practice patterns for children undergoing adenotonsillectomy. The main measure was survey responses from the division chiefs of pediatric otolaryngology reporting group practice. RESULTS: The survey response rate was 46%. Eighty-eight percent of groups reported an official adenotonsillectomy admission policy. Commonly reported admission criteria included age (93%) and obesity (59%). Eighty-eight percent of groups defined severe obstructive sleep apnea as apnea-hypopnea index ≥10. Only 41% of groups required a child to be observed sleeping on room air prior to ambulatory discharge. Ninety-seven percent of groups reported routinely obtaining preoperative polysomnography in a variety of clinical settings. CONCLUSIONS: Many children's hospitals report an official admission policy following adenotonsillectomy. Despite a decade passing since the initial publication of the American Academy of Otolaryngology-Head and Neck Surgery clinical practice guidelines, there remains great variability in the practice patterns for both preoperative polysomnography and postoperative monitoring and admission. These results highlight an opportunity for an improved unified approach to perioperative pediatric adenotonsillectomy practice. LEVEL OF EVIDENCE: 5 Laryngoscope, 2023.

Systematic Review of Laryngeal Fractures and Trends in Operative Management.

Study Design: Systematic review of the literature. Objective: The goal of this study is to review the current literature on the trends in management of laryngeal fractures following trauma. Methods: Independent searches of the PubMed and MEDLINE databases were performed. Articles from the period of 1963 to 2020 were collected. All studies which described laryngeal fractures using the Boolean method and relevant search term combinations, including "Laryngeal", "Fracture", "Operative", and "Management" were collected. Results: A total of 588 relevant unique articles were identified for analysis. Of these, 24 articles were deemed appropriate for inclusion in the literature review. Due to variability in study design and outcome measures, formal synthesis of data in the form of a meta-analysis was not possible. Conclusions: Laryngeal fractures are rare traumatic injuries that require early identification and evaluation with complex management options. This comprehensive review aims to highlight the breadth of the topic with regard to presentation and clinical management. Though there remains no clear best practice for laryngeal fracture management, we review trends in clinical practice throughout the literature.

Emergency Cricothyrotomy: A 10-Year Single Institution Experience.

BACKGROUND: With recent technological advances reducing the demand for emergent surgical airway placement, surgeons are less often performing this life-saving procedure. We sought to assess the characteristics and outcomes surrounding patients undergoing modern emergent cricothyrotomy. METHODS: A retrospective case series was performed between January 2010 and January 2020 at a single tertiary academic level 1 trauma center. Patients who underwent tracheostomy (CPT 31600, 31601) within 48 hours of admission or listed in the trauma registry were queried. Charts were individually reviewed to identify patients with cricothyrotomy. Demographic, operative and relevant hospital course data were collected. RESULTS: A total of 1642 patients were identified with 12 of those found to have met inclusion criteria. The population was mostly male (91.7%) with an average age of 43 years and average body mass index of 30. Survival rate of patients was 75%. A total of 7 patients (58%) had appropriate anatomical placement of cricothyrotomy. Of those patients, 75% were performed by Trauma Surgery. Of the 5 patients with misplaced cricothyrotomy, all were male, with an average age and body mass index of 36 years and 25, respectively. Procedures were performed by prehospital personnel (20%), referring hospital (20%), and Trauma Surgery (60%). DISCUSSION: Cricothyrotomy remains a vital tool in the successful management of emergent airway access. The most common complication observed was improper anatomical placement, which occurred in nearly half of patients. Trauma surgeons perform 75% of cricothyrotomies, with an anatomical accuracy rate of 66.7%.

Postoperative Outcomes in Pediatric Septoplasty.

OBJECTIVE: Identify risk factors and perioperative morbidity for pediatric patients undergoing septoplasty. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Pediatric (NSQIP-P) database was retrospectively queried to identify patients who underwent septoplasty (CPT 30520) for a diagnosis of deviated nasal septum (ICD J34.2) from 2018 to 2019. Outcomes analyzed include patient demographics, medical comorbidities, surgical setting, operative characteristics, length of stay, and postoperative outcomes. RESULTS: A total of 729 children were identified. Median age at time of surgery was 15.8 years, with most patients (82.8%) >12 years of age; no significant association was identified between age at time of surgery and adverse surgical outcomes. Overall, postoperative complications were uncommon (0.6%), including readmission (0.4%), septic shock (0.1%), and surgical site infection (0.1%). A history of asthma was found to be a significant risk factor for postoperative complications (P = .035) as well as BMI (P = .028). CONCLUSION: The 30-day postoperative complications following pediatric septoplasty in children reported in the NSQIP-P database are infrequent. Special considerations regarding young age, complex sinonasal anatomy, and surgical technique remain important features in considering corrective surgery for the pediatric nose and certainly warrant further investigation in subsequent studies.

Prevalence of Body Dysmorphic Disorder in an Otolaryngology-Head and Neck Surgery Clinic.

OBJECTIVE: To analyze the prevalence of body dysmorphic disorder (BDD) in a general otolaryngology population presenting to an outpatient clinic. STUDY DESIGN: Prospective prevalence study. SETTING: Single tertiary academic otolaryngology clinic. SUBJECT AND METHODS: New patients over 18 years of age who presented to an academic otolaryngology clinic between August 2018 and May 2021 completed a questionnaire including demographic questions and the validated Body Dysmorphic Disorder Questionnaire (BDDQ). Data collected from the questionnaires were analyzed to assess demographics and prevalence of BDD in an otolaryngology clinic. RESULTS: Of the 242 patients queried, 15 patients screened positive for BDD. The screened prevalence of BDD was determined to be 6.2%. None of the patients had previously been diagnosed with BDD. The prevalence of prior mental health diagnoses was 34.3%. These patients had initially presented for a variety of otolaryngologic concerns and had pre-existing diagnoses of anxiety, depression, obsessive-compulsive, bipolar and eating disorders. CONCLUSION: The prevalence of BDD in our population of new patients presenting to an academic otolaryngology practice (6.2%) is higher than that of the general population (1.9%).

Pediatric Dysphagia.

Feeding difficulty is common in the pediatric population, particularly in at-risk infants, such as those born prematurely. Appropriate work-up should involve a multidisciplinary team and may commonly use modified barium swallow and flexible endoscopic evaluation of swallow, in addition to history and physical examination. Structural causes of dysphagia may involve surgical management, whereas nonstructural causes may invoke medical therapies. If symptoms do not resolve following intervention, it is important to revisit the interdisciplinary team, because dysphagia is commonly multifactorial in origin. Appropriate identification and early intervention are necessary for successful outcomes in growth and development for children.

Lymphatic malformations: a 20-year single institution experience.

PURPOSE: Lymphatic malformations (LMs) are congenital abnormalities which result from disturbances in the embryologic development of the lymphatic system. We sought to determine the characteristics and treatment patterns for LMs in a rural setting, and the effect of a specialized vascular malformations clinic on triage and follow-up. METHODS: This is a retrospective cohort study at a single tertiary care institution. Sixty-two patients were identified; chart review was completed to obtain demographic, surgery/sclerotherapy session and follow-up information. RESULTS: The head/neck region was the most predominant LM location (N = 26, 41.9%), followed by trunk (N = 16, 25.8%), extremity (N = 11, 17.7%), and intraabdominal/retroperitoneal (N = 7, 11.3%). Twenty-eight patients were managed non-surgically, while 21, 7 and 6 patients required surgery, sclerotherapy, or both. Head/neck LMs were the most likely to recur (73%, p = 0.028). Patients seen in specialty clinic had similar duration of follow-up and time to intervention, but were more often below 1 year of age (p = 0.030). Average LM volume among patients with available imaging was much larger in those referred to specialty clinic (73.2 cm3 versus 14.8 cm3, p = 0.022). CONCLUSION: Our experience reiterates not only the wide variety of clinical presentations of lymphatic malformations, but also demonstrates the necessity of multiple subspecialties and their collaboration to achieve prompt and efficacious treatment.

Usage Patterns of CT and MRI in the Evaluation of Otologic Disease.

OBJECTIVE: To evaluate the current trends and usage patterns of radiographic imaging for otologic disease by specialty, length of practice, practice setting, geographic region, and pediatric volume. STUDY DESIGN: Cross-sectional study. SETTING: Survey of physicians. SUBJECTS: General Otolaryngologists and Otologists/Neurotologists (O/N) of the American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS). METHODS AND OUTCOME MEASURES: An electronic questionnaire was distributed to AAO-HNS members. Respondents were separated into groups by specialty, length of practice, practice setting, region, and pediatric exposure. Chi-square tests were performed for the determination of significance. RESULTS: The survey was sent to 5,168 members of AAO-HNS. The response rate was 10.6% (n = 546) and 18.1% for only O/N (n = 143). Most respondents were generalists (74%), in practice >20 years (51%), with a primarily adult practice (95%). O/N were more often academics (44 versus 17% combined, 40% private; p < 0.001) and saw fewer children (80 fewer than 25%; p < 0.001). Compared with generalists, O/N were more likely to respond with more frequent and earlier magnetic resonance imaging (MRI) utilization in the workup of the majority of otologic diseases. Significant differences in usage patterns for various conditions were demonstrated across all categories, but specialty training was the most common. Generalists (34 versus 12% of O/N; p < 0.001), physicians practicing >20 years (32 versus 18% of < 5 yrs; p = 0.006), and private practice physicians (34 versus 14-20% of others; p < 0.001) relied more heavily on the radiology report to interpret MRI scans. CONCLUSION: Subspecialty training seems to be the main variable correlating with significant differences in the use of MRI and computed tomography imaging in patients with otologic disease.

30-Day Postoperative Outcomes Following Transcervical Zenker's Diverticulectomy in the Elderly: Analysis of the NSQIP Database.

OBJECTIVE: To compare the effect of patient factors, including age, on 30-day postoperative outcomes and complications for patients undergoing transcervical Zenker's diverticulectomy. STUDY DESIGN: Retrospective cross-sectional analysis. SETTING: American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Database. METHODS: Patients who underwent open Zenker's diverticulectomy (Current Procedural Terminology code 43130) were queried via the NSQIP (2006-2018). Outcomes analyzed include patient demographics, medical comorbidities, admission type, operative characteristics, length of admission, postoperative complication, readmission, and reoperation. RESULTS: A total of 614 patients were identified. Mean age at time of surgery was 71.1 years, with 13.4% older than 85 years. Outpatient procedures were performed in 29.8%. Postoperative complications occurred in 6.7%, with reoperation and readmission rates of 6.4% and 7.2%, respectively. A mortality rate of 0.3% was observed. Only smoking status (odds ratio, 2.94; P = .008) and history of congestive heart failure (odds ratio, 10.00; P = .014) were shown to have a significant effect on postoperative complications. CONCLUSION: Smoking status confers a high risk for postoperative complication. Age was not an independent risk factor associated with adverse outcomes following open diverticulectomy, suggesting this procedure can be safely performed in patients with advanced age.

Postoperative Outcomes of Branchial Cleft Cyst Excision in Children and Adults: An NSQIP Analysis.

OBJECTIVE: Identify risk factors and perioperative morbidity for patients undergoing branchial cleft cyst (BCC) excision. STUDY DESIGN: Cross-sectional analysis. SETTING: American College of Surgeons National Surgical Quality Improvement Program adult and pediatric databases (NSQIP and NSQIP-P). SUBJECT AND METHODS: Patients who underwent BCC excision (Current Procedural Terminology 42810, 42815) were queried via NSQIP (2005-2016) and NSQIP-P (2012-2016). Outcomes analyzed include patient demographics, medical comorbidities, admission type, operative characteristics, length of hospital stay, postoperative complications, and readmission. RESULTS: A total of 1775 children and 677 adults were identified. Mean age at time of surgery was 4.6 years for children and 38.6 years for adults. Outpatient procedures were performed in 87.1% of adults and 94.0% of children (P < .001). Postoperative complications were uncommon, occurring in <1% of adults and 3.9% of children (P < .001). Similarly, readmission occurred in 1.2% of adults and 1.1% of children. In adults, smoking status was shown to have a significant effect on postoperative complications (odds ratio, 6.25; P = .037). Age group did not have an effect on the complication rate in the pediatric population. Pediatric otolaryngologists had higher rates of postoperative complications (P = .001), prolonged operative times (P < .001), and fewer outpatient procedures (P < .001). Conversely, in adults, otolaryngologists had fewer postoperative complications. CONCLUSION: Postoperative complications following BCC excision are relatively uncommon, demonstrating procedural safety when performed at any age.

Post-tonsillectomy respiratory complications in children with sleep disordered breathing.

OBJECTIVE: A common indication for tonsillectomy in children is clinically diagnosed sleep disordered breathing (SDB) without confirmation of obstructive sleep apnea (OSA) by polysomnography (PSG). Our goal was to review rates of post-tonsillectomy respiratory complications in children with SDB without prior PSG in order to develop recommendations for postoperative monitoring and safe hospital discharge in this population. METHODS: Following Institutional Review Board (IRB) approval at Penn State Milton S. Hershey Medical Center, a database query using Current Procedural Terminology (CPT) codes for tonsillectomy with or without adenoidectomy (42820, 42821, 42825, 42826) between January 1, 2012 and December 31, 2017 was performed. International Classification of Diseases (ICD) codes for sleep disordered breathing (G47.30), snoring (R06.83), and obstructive sleep apnea (G47.33) were applied for further selection. Charts were individually reviewed to confirm the inclusion criteria of pediatric patients (≤18 years) who underwent tonsillectomy without prior PSG and were monitored overnight. Demographic, operative, and relevant postoperative hospital course data (including desaturations, supplemental oxygen requirements, and upgraded level of care) were collected. RESULTS: A total of 1874 unique patient encounters were identified by our database search and 364 children met inclusion criteria. The average age of the patient population was 6.5 ± 3.1 years and 52.2% of children were female. Mean z-score for the population was 0.6. The rate of overnight oxygen desaturation events (<95%) was 2.2%, with no severe complications found in this population. Children with desaturation events were supplemented with oxygen and resolved prior to hospital discharge. Only race was found to be significantly related to risk of mild overnight desaturations (P = 0.023). CONCLUSION: A lack of significant postoperative respiratory complications or alterations in the clinical management of children with SDB without prior PSG supports the idea that such patients may safely be discharged from the hospital following tonsillectomy without overnight oxygen monitoring.

The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia.

BACKGROUND: Transcript levels for cytokines and the viral restriction factor interferon-induced transmembrane protein are markedly higher in the prefrontal cortex in schizophrenia. These gene products are regulated by the nuclear factor-κB (NF-κB) transcriptional complex. NF-κB activity, which requires the formation of NF-κB family member heterodimers, is regulated by activation receptors, kinases, and inhibitors. Whether any of these factors are altered in schizophrenia is not known. It is also unclear whether NF-κB-related disturbances reflect ongoing cortical immune activation or a long-lasting response to a prenatal immune-related insult. METHODS: Transcript levels for NF-κB pathway markers were assessed using quantitative polymerase chain reaction in the prefrontal cortex from 1) 62 matched pairs of schizophrenia and unaffected comparison subjects, 2) antipsychotic-exposed monkeys, and 3) adult mice exposed prenatally to maternal immune activation or in adulthood to the immune stimulant polyinosinic-polycytidylic acid. RESULTS: In schizophrenia subjects, but not antipsychotic-exposed monkeys, we found higher messenger RNA levels for 1) most NF-κB family members, 2) all NF-κB activation receptors, 3) several kinases, and 4) one inhibitor (IκBα) whose transcript level is itself regulated by NF-κB activity. A similar pattern of elevated NF-κB-related messenger RNA levels was seen in adult mice that received daily polyinosinic-polycytidylic acid injections, but not in adult mice subjected to maternal immune activation in utero. CONCLUSIONS: Higher NF-κB activity, evidenced by elevated transcript levels for NF-κB family members, activation receptors, and kinases, may contribute to increased markers of cortical immune activation in schizophrenia.

Head and Neck Manifestations of Systemic Disease.

Systemic diseases commonly managed by the Internist may have presentations within the head and neck. Awareness of these manifestations, sometimes as the presenting signs or symptoms of systemic disease, may aid the Internist in diagnosis and management. The Otolaryngologist may be helpful in assisting in the evaluation of these patients and in some cases providing targeted symptomatic therapy. Some systemic processes can generate emergent airway events, and early engagement of the otolaryngologist is of value.

Molecular mechanisms and timing of cortical immune activation in schizophrenia.

OBJECTIVE: Immune-related abnormalities are commonly reported in schizophrenia, including higher mRNA levels for the viral restriction factor interferon-induced transmembrane protein (IFITM) in the prefrontal cortex. The authors sought to clarify whether higher IFITM mRNA levels and other immune-related disturbances in the prefrontal cortex are the consequence of an ongoing molecular cascade contributing to immune activation or the reflection of a long-lasting maladaptive response to an in utero immune-related insult. METHOD: Quantitative polymerase chain reaction was employed to measure mRNA levels for immune-related cytokines and transcriptional regulators, including those reported to regulate IFITM expression, in the prefrontal cortex from 62 schizophrenia and 62 healthy subjects and from adult mice exposed prenatally to maternal immune activation or in adulthood to the immune stimulant poly(I:C). RESULTS: Schizophrenia subjects had markedly higher mRNA levels for interleukin 6 (IL-6) (+379%) and interferon-ß (+29%), which induce IFITM expression; lower mRNA levels for Schnurri-2 (-10%), a transcriptional inhibitor that lowers IFITM expression; and higher mRNA levels for nuclear factor-κB (+86%), a critical transcription factor that mediates cytokine regulation of immune-related gene expression. In adult mice that received daily poly(I:C) injections, but not in offspring with prenatal exposure to maternal immune activation, frontal cortex mRNA levels were also markedly elevated for IFITM (+304%), multiple cytokines including IL-6 (+493%), and nuclear factor-κB (+151%). CONCLUSIONS: These data suggest that higher prefrontal cortex IFITM mRNA levels in schizophrenia may be attributable to adult, but not prenatal, activation of multiple immune markers and encourage further investigation into the potential role of these and other immune markers as therapeutic targets in schizophrenia.