Upper Airway Stimulation in Female Patients: Safety and Efficacy of a Novel Lateral Approach.

OBJECTIVE: To describe a novel lateral approach for hypoglossal nerve stimulator (HNS) implantation in women and provide evidence for its safety and efficacy. STUDY DESIGN: Retrospective case series. SETTING: Single academic medical center. METHODS: We identified patients implanted with HNS by a single surgeon from January 2017 to December 2021. Patient characteristics, postoperative complications, surgical duration, response to therapy, and need for revision surgery were recorded. RESULTS: One hundred four patients were included, including 93 males and 11 females. The lateral approach for HNS implantation involves placing the chest incision for the implantable pulse generator and respiratory sensor lead vertically in the anterior axillary line instead of horizontally in the infraclavicular area. No changes are made to the stimulator lead placement. All female patients were implanted using a lateral approach and all male patients were implanted via the standard anterior approach. Half of the patients were implanted via a 2-incision technique. The median surgical time duration was equivalent in male and female patients (119 [interquartile range (IQR): 105-138] vs 126 [IQR: 115-141], respectively). Revision was required in 2 (18%) females versus 6 (6%) males (p = .17). There were equivalent rates of therapy response as well as postoperative complications. CONCLUSION: A more cosmetic lateral approach is feasible for HNS in female patients and has a similar rate of adverse events and therapy responsiveness. Additional considerations in female patients include the ability to tolerate mammography as well as HNS implantation in the setting of existing breast implants.

Predictors of surgical complications in patients with sinonasal malignancy.

OBJECTIVES: Sinonasal and skull base tumors are rare, making it difficult to identify trends in surgical outcome. This study examines complications in a large cohort of patients undergoing surgery for sinonasal malignancy. METHODS: Following IRB approval, an institutional database was reviewed to identify patients who underwent surgery for sinonasal or skull base malignancies from 1973 to 2016 at our institution. Charlson comorbidity index score and Clavien-Dindo grade were calculated. The main study endpoint was subgroup analysis of Clavien-Dindo Grade 0, Grades 1-2, and Grades 3-5 complications. An ordinal logistic regression model was constructed to assess the association between comorbidities, demographics, tumor characteristics, and surgical complications. RESULTS: In total, 448 patients met inclusion criteria. Perioperative mortality rate at 30 days was 1.6% (n = 7). The rate of severe complications (Clavien-Dindo 3 or higher) was 13.6% (n = 61). Multivariate analysis using an ordinal logistic regression model showed no association between Charlson comorbidity index score and Clavien-Dindo grade of postoperative complication. Advanced T-stage was significantly associated with complications (p = 0.0014; odds ratio: 3.442 [95% confidence interval: 1.615, 7.338]). CONCLUSION: Surgery for sinonasal and skull base tumors is safe with a low mortality rate. Advanced T-stage is associated with postoperative complications. These findings have implications for preoperative risk stratification. Key Points Surgery for sinonasal malignancy is safe with a 30 mortality of 1.6% and rate of severe complications of 12.8%. There is no association between patient comorbidity and post operative complication. On multivariate analysis, only advanced T stage was associated with increased rate of surgical complication.

Gender as a Predictor of Complications in Endoscopic Sinus Surgery.

BACKGROUND: Understanding patient-specific risk factors for complications of functional endoscopic sinus surgery (ESS) is critical. Previous work has investigated such risk factors, but a population-based analysis has not been performed to date. OBJECTIVES: This study analyzes the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to identify patient-specific risk factors associated with complications following ESS. METHODS: A retrospective cohort study of patients who underwent ESS was conducted using the NSQIP database from 2011 to 2017. Patients were identified using CPT-codes for ESS procedures. The primary outcome analyzed was any postoperative complication. Simultaneous procedures with ESS were controlled for with regression analysis. Post-operative complications and 30-day readmission were evaluated using multivariate logistic regression controlling for age, gender, race, comorbidities (diabetes mellitus, hypertension, chronic obstructive pulmonary disease, congestive heart failure, renal failure, steroid use, and cancer history), smoking history, and intraoperative factors. RESULTS: A total of 1279 patients who underwent ESS were identified. The average age of patients was 46.1 (SD = 16.8). Most patients (58.2%) had no major comorbidities. 594 (46.4%) patients had a tonsillectomy, adenoidectomy, or uvulopharyngoplasty at the same time as ESS. 101 (7.9%) patients experienced a complication post-operatively. 46 (3.6%) patients experienced a readmission postoperatively. The most common complication was reoperation (N = 40, 3.1%). Regression analysis revealed that gender was the only demographic factor associated with risk of post-operative complications, with women having a significantly lower risk than men (OR = 0.61, 95% CI 0.37-0.99, P = .046). CONCLUSIONS: ESS is typically performed on a relatively young and healthy population. Women have a significantly lower risk of complications after controlling for comorbidities. Further analysis of gender-specific differences in surgical outcomes should be evaluated to understand this phenomenon.

Recurrent Laryngeal Nerve Reinnervation in Rats Posttransection: Neurotrophic Factor Expression over Time.

OBJECTIVE: Recurrent laryngeal nerve (RLN) injury causes vocal fold paralysis from which functional recovery is typically absent due to nonselective reinnervation. This study investigates expression of axon guidance cues and their modulators relative to the chronology of reinnervation by examining the expression of glial-derived neurotrophic factor (GDNF), netrin 1, and laminin 111 (LAMA1) in nonpooled laryngeal muscles. This study is the first to describe the post-RLN injury expression pattern of LAMA1, a target of particular interest as it has been shown to switch netrin 1-mediated growth cone attraction to repulsion. STUDY DESIGN: Animal experiment (rat model). SETTING: Basic science laboratory. METHODS: The right RLNs of 64 female Sprague-Dawley rats were transected, with sacrifice at 1, 3, 7, 21, 28, and 56 days postinjury (DPI). Single-animal messenger RNA was isolated from the ipsilateral posterior cricoarytenoid (PCA), lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA) for quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Immunostaining for LAMA1 expression was performed in the same muscles. RESULTS: LAMA1 was elevated in the PCA at 3 to 56 DPI, LTA at 7 DPI, and MTA at 14 and 28 DPI. This correlates with the chronology of laryngeal reinnervation. Using a new protocol, single-animal muscle qRT-PCR possible and expression results for GDNF and netrin 1 were similar to previous pooled investigations. CONCLUSION: Reliable qRT-PCR is possible with single rat laryngeal muscles. The expression of netrin 1 and LAMA1 is chronologically coordinated with muscle innervation in the LTA and MTA. This suggests that LAMA1 may influence netrin 1 to repel axons and delay LTA and MTA reinnervation.

Differences in postoperative maladaptive behavioral changes between partial and total tonsillectomy patients.

INTRODUCTION: Behavioral difficulties associated with sleep-disordered breathing (SDB) improve after tonsillectomy, but surgery may lead to the development of short-term postoperative maladaptive behavioral changes (PMBCs). These PMBCs have not been compared between total and partial tonsillectomy patients. METHODS: SDB patients aged 1-6 years undergoing tonsillectomy were recruited. Parent phone surveys were conducted at 48-72 hours and 1-2 weeks postoperatively. Parents identified PMBCs using the Post-Hospital Behavior Questionnaire (PHBQ), scoring changes in behavior compared to baseline. PMBCs were defined by PHBQ scores >0 and compared by one-tailed t-test. Postoperative pain was categorized as mild, moderate, and severe pain using the Parents' Postoperative Pain Measure (PPPM). Differences in pain levels were analyzed by Chi-squared test. A p-value <0.05 was deemed statistically significant. RESULTS: Seventy-eight children completed the study, with 29 total tonsillectomy and 49 partial tonsillectomy patients. At both time points after surgery, PHBQ scores were higher in total tonsillectomy patients than in partial tonsillectomy patients (3.41 ±â€¯3.53 versus 1.94 ±â€¯2.25 at 2-3 days, p = .013). PMBCs were also more frequent in total than partial tonsillectomy patients (76% versus 59% at 2-3 days; 28% versus 7% at 1-2 weeks). Meanwhile, distribution of pain levels was similar between both partial and total tonsillectomy patients. CONCLUSIONS: Our study indicates that total tonsillectomy patients more frequently experience PMBCs than do partial tonsillectomy patients despite similar distributions in pain levels postoperatively. This difference in PHBQ scores between total and partial tonsillectomy patients should be further explored.

Investigation of the presence of HPV on KTP laser fibers following KTP laser treatment of papilloma.

OBJECTIVES: Recurrent respiratory papillomatosis is often treated with in-office laser procedures using a potassium titanyl phosphate (KTP) laser transmitted through a laser fiber. Although effective, this procedure has notable downsides, including the possibility of transmitting human papillomavirus (HPV) in the smoke plume and the high cost of these single-use fibers. The objective of this study is to determine if HPV can be detected on a laser fiber after use, with or without sterilization. METHODS: Twelve patients with laryngeal papillomas were treated with KTP laser energy transmitted via a KTP fiber. Ten fibers were sterilized in CIDEX (ASP, Irvine, California), a glutaraldehyde disinfectant, for 12 minutes, whereas two fibers were left unsterilized. Human papillomavirus DNA amplification was done on all 12 fiber samples with real-time polymerase chain reaction (PCR) using general primer mediated 5+ and 6+. Human papillomavirus genotyping detection was done using type specific probes and/or Sanger sequencing. RESULTS: Over 27 strains of HPV were not detected on KTP fibers after use, with or without sterilization. CONCLUSION: Human papillomavirus was undetectable by PCR on KTP laser fibers that were sterilized or unsterilized after use. Further studies are needed utilizing a transmission model to determine if HPV can be incubated from this fiber after sterilization. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:926-928, 2018.

ACSS2 gene variant associated with cleft lip and palate in two independent Hispanic populations.

OBJECTIVES/HYPOTHESIS: A candidate variant (p.Val496Ala) of the ACSS2 gene (T > C missense, rs59088485 variant at chr20: bp37 33509608) was previously found to consistently segregate with nonsyndromic cleft lip and/or palate (NSCLP) in three Honduran families. Objectives of this study were 1) to investigate the frequency of this ACSS2 variant in Honduran unrelated NSCLP patients and unrelated unaffected controls and 2) to investigate the frequency of this variant in Colombian unrelated affected NSCLP patients and unrelated unaffected controls. STUDY DESIGN: Case-control studies. METHODS: Sanger sequencing of 99 unrelated Honduran NSCLP patients and 215 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. Sanger sequencing of 230 unrelated Colombian NSCLP patients and 146 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. RESULTS: In the Honduran population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 4.0 (P = .03), with a carrier frequency of seven of 99 (7.1%) in unrelated affected and four of 215 (1.9%) in unrelated unaffected individuals. In the Colombian population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 2.6 (P = .04), with a carrier frequency of 23 of 230 (10.0%) in unrelated affected and six of 146 (4.1%) in unrelated unaffected individuals. CONCLUSIONS: These findings support the role of ACSS2 in NSCLP in two independent Hispanic populations from Honduras and Colombia. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E336-E339, 2017.

Dysregulations in the PI3K pathway and targeted therapies for head and neck squamous cell carcinoma.

The phosphoinositide 3-kinase (PI3K) signaling pathway is the most commonly mutated pathway in head and neck squamous cell carcinoma (HNSCC). There are several drugs targeting members of the PI3K signaling pathway in development for HNSCC. In this article, we review the genetic alterations reported in the pathway pertinent to HNSCC, various agents in development targeting various mediators of the pathway, results from clinical trials, and remaining challenges in the development of PI3K pathway inhibitors.

Brain dynamics of post-task resting state are influenced by expertise: Insights from baseball players.

Post-task resting state dynamics can be viewed as a task-driven state where behavioral performance is improved through endogenous, non-explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post-task resting state dynamics that promote learning. We measured simultaneous fMRI/EEG and DTI in Division-1 collegiate baseball players and compared to a group of controls, examining differences in both functional and structural connectivity. Participants performed a surrogate baseball pitch Go/No-Go task before a resting state scan, and we compared post-task resting state connectivity using a seed-based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Although both groups were equally trained on the task, the experts showed differential activity in their post-task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA-L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD-alpha oscillation correlations between groups suggests variability in modulatory attention in the post-task state, and (3) group differences between BOLD-beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find that brain dynamics in the post-task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity. Hum Brain Mapp 37:4454-4471, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei.

The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic-pituitary-adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25mg/kg) or OXT antagonist (OXT-A, 20mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors.

Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder.

Generalized social anxiety disorder (GSAD) is characterized by aberrant patterns of amygdala-frontal connectivity to social signals of threat and at rest. The neuropeptide oxytocin (OXT) modulates anxiety, stress, and social behaviors. Recent functional neuroimaging studies suggest that these effects are mediated through OXT's effects on amygdala reactivity and/or amygdala-frontal connectivity. The aim of the current study was to examine OXT's effects on amygdala-frontal resting-state functional connectivity (rsFC) in GSAD patients and healthy controls (HCs). In a randomized, double-blind, cross-over design, 18 GSAD and 18 HC participants received intranasal OXT (24 IU or 40.32 µg) or placebo (PBO) before resting-state functional magnetic resonance imaging. In individuals with GSAD, OXT enhanced rsFC of the left and right amygdala with rostral anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC), and in doing so, reversed (ie, 'normalized') the reduced amygdala-frontal connectivity observed relative to HCs evident on PBO. Higher social anxiety severity in GSAD subjects correlated with lower amygdala-ACC/mPFC connectivity on PBO and higher social anxiety also correlated with greater enhancement in amygdala-frontal connectivity induced by OXT. These findings show that OXT modulates a neural circuit known for social threat processing and emotion regulation, suggesting a neural mechanism by which OXT may have a role in the pathophysiology and treatment of social anxiety disorder.