Adverse events associated with anastomotic coupling devices in microvascular reconstruction.

OBJECTIVE: In light of the recent US Food and Drug Administration (FDA) Class 2 safety recall notice for anastomotic coupling devices, it is important to understand related adverse events. The aim of this study was to characterize adverse events in anastomotic coupling devices for microvascular reconstruction. METHODS: A retrospective cross-sectional analysis using the 2011 to 2021 US FDA Manufacturer and User Facility Device Experience (MAUDE) database. All reports of adverse events involving anastomotic coupling devices were retrieved from the MAUDE database. Descriptive statistics were used to analyze categorized events. RESULTS: There were a total of 293 documented adverse events related to anastomotic coupling devices. These adverse events resulted in 91 (31.1 %) patient injuries and 239 (81.6 %) device malfunctions. The most frequent patient problems were thrombosis/hematoma (n = 38; 41.8 %), unspecified injury (n = 31; 34.1 %), and failure to anastomose (n = 13; 14.3 %). Free flap necrosis was reported in 42 % of thrombosis/hematoma cases (n = 16). The most common malfunctions were devices operating differently than expected (n = 74; 31.0 %), connection problems (n = 41; 17.2 %), and twisted/bent material (n = 19; 7.9 %). There was no significant trend in the number of adverse events over the study period (p > 0.05). CONCLUSIONS: Adverse events from anastomotic coupling devices represent an important and modifiable factor in free tissue failure. Adverse events are predominately related to devices operating differently than expected and may result in vascular compromise of the free flap. Reconstructive surgeons should be cognizant of defective anastomotic coupling devices and be prepared to utilize traditional hand-sewn anastomosis.

Margin Assessment Methods in Oral Cavity Squamous Cell Carcinoma and Recurrence: Tumor Bed vs Resection Specimen Sampling.

Importance: Positive margins and margin clearance are risk factors for recurrence in oral cavity squamous cell carcinoma (OCSCC), and these features are used to guide decisions regarding adjuvant radiation treatment. However, the prognostic value of intraoperative tumor bed vs resection specimen sampling is not well defined. Objective: To determine the prognostic implications of intraoperative margin assessment methods (tumor bed vs resection specimen sampling) with recurrence among patients who undergo surgical resection for OCSCC. Design, Setting, and Participants: This was a retrospective study of patients who had undergone surgical resection of OCSCC between January 1, 2000, and December 31, 2021, at a tertiary-level academic institution. Patients were grouped by margin assessment method (tumor bed [defect] or resection specimen sampling). Of 223 patients with OCSCC, 109 patients had localized tumors (pT1-T2, cN0), 154 had advanced tumors, and 40 were included in both cohorts. Disease recurrence after surgery was estimated by the cumulative incidence method and compared between cohorts using hazard ratios (HRs). Data analyses were performed from January 5, 2023, to April 30, 2023. Main Outcome and Measures: Recurrence-free survival (RFS). Results: The study population comprised 223 patients (mean [SD] age, 62.7 [12.0] years; 88 (39.5%) female and 200 [90.0%] White individuals) of whom 158 (70.9%) had defect-driven and 65 (29.1%) had specimen-driven margin sampling. Among the 109 patients with localized cancer, intraoperative positive margins were found in 5 of 67 (7.5%) vs 8 of 42 (19.0%) for defect- vs specimen-driven sampling, respectively. Final positive margins were 3.0% for defect- (2 of 67) and 2.4% for specimen-driven (1 of 42) margin assessment. Among the 154 patients with advanced cancer, intraoperative positive margins were found in 29 of 114 (25.4%) vs 13 of 40 (32.5%) for defect- and specimen-driven margins, respectively. Final positive margins were higher in the defect-driven group (9 of 114 [7.9%] vs 1 of 40 [2.5%]). When stratified by margin assessment method, the 3-year rates of local recurrence (9.7% vs 5.1%; HR, 1.37; 95% CI, 0.51-3.66), regional recurrence (11.0% vs 10.4%; HR, 0.85; 95% CI, 0.37-1.94), and distant recurrence (6.4% vs 5.0%; HR, 1.10; 95% CI, 0.36-3.35) were not different for defect- vs specimen-driven sampling cohorts, respectively. The 3-year rate of any recurrence was 18.9% in the defect- and 15.2% in the specimen-driven cohort (HR, 0.93; 95% CI, 0.48-1.81). There were no differences in cumulative incidence of disease recurrence when comparing defect- vs specimen-driven cases. Conclusions and Relevance: The findings of this retrospective cohort study indicate that margin assessment methods using either defect- or specimen-driven sampling did not demonstrate a clear association with the risk of recurrence after OCSCC resection. Specimen-driven sampling may be associated with reduced surgical margin positivity rates, which often necessitate concurrent chemotherapy with adjuvant radiation therapy.

Association of Treatment Strategies and Tumor Characteristics With Overall Survival Among Patients With Anaplastic Thyroid Cancer: A Single-Institution 21-Year Experience.

Importance: Survival outcomes for anaplastic thyroid cancer (ATC), the most aggressive subtype of thyroid cancers, have remained poor. However, targeted therapies and immunotherapies present new opportunities for treatment of this disease. Evaluations of survival outcomes over time with new multimodal therapies are needed for optimizing treatment plans. Objective: To evaluate the association of treatment strategies and tumor characteristics with overall survival (OS) among patients with ATC. Design, Setting, and Participants: This retrospective case series study evaluated the survival outcomes stratified by treatment strategies and tumor characteristics among patients with ATC treated at a tertiary level academic institution from January 1, 2000, to December 31, 2021. Demographic, tumor, treatment, and outcome characteristics were analyzed. Kaplan-Meier method and log rank test modeled OS by treatment type and tumor characteristics. Data were analyzed in May 2022. Main Outcomes and Measures: Overall survival (OS). Results: The study cohort comprised 97 patients with biopsy-proven ATC (median [range] age at diagnosis, 70 [38-93] years; 60 (62%) female and 85 [88%] White individuals; 59 [61%] never smokers). At ATC diagnosis, 18 (19%) patients had stage IVA, 19 (20%) had stage IVB, and 53 (55%) had stage IVC disease. BRAF status was assessed in 38 patients; 18 (47%) had BRAF-V600E variations and 20 (53%), BRAF wild type. Treatment during clinical course included surgery for 44 (45%) patients; chemotherapy, 41 (43%); definitive or adjuvant radiation therapy, 34 (RT; 35%); and targeted therapy, 28 (29%). Median OS for the total cohort was 6.5 (95% CI, 4.3-10.0) months. Inferior OS was found in patients who did not receive surgery (hazard ratio [HR], 2.12; 95% CI, 1.35-3.34; reference, received surgery), chemotherapy (HR, 3.28; 95% CI, 1.99-5.39; reference, received chemotherapy), and definitive or adjuvant RT (HR, 2.47; 95% CI, 1.52-4.02; reference, received definitive/adjuvant RT). On multivariable analysis, age at diagnosis (HR, 1.03; 95% CI, 1.01-1.06), tumor stage IVC (HR, 2.65; 95% CI, 1.35-5.18), and absence of definitive or adjuvant RT (HR, 1.90; 95% CI, 1.01-3.59) were associated with worse OS. Conclusions and Relevance: This retrospective single-institution study found that lower tumor stage, younger age, and the ability to receive definitive or adjuvant RT were associated with improved OS in patients with ATC.

Laryngology Outcomes Following Implantable Vagus Nerve Stimulation.

Importance: Vagus nerve stimulation (VNS) devices have gained widespread acceptance for treatment of resistant epilepsy and depression. The increasing number of procedures has resulted in an increasing number of iatrogenic injuries to the vagus nerve, which can have a significant effect on vocalization and quality of life. Objective: To determine the relative frequency of laryngeal adverse effects reported to the US Food and Drug Administration (FDA) after VNS implantation and to analyze associated VNS device problems. Design, Setting, and Participants: This retrospective cross-sectional analysis queried the FDA Manufacturer and User Facility Device Experience database of adverse events in the US between 1996 and 2020. Main Outcomes and Measures: The primary outcome was the percent of adverse events reported to the FDA that included patients who received VNS with laryngeal adverse effects and the associated proportion of device problems after VNS surgery. Results: A total of 12 725 iatrogenic vagus nerve issues were documented after VNS implantation, with apnea (n = 395; 3.1%) being the most common patient problem. Overall, 187 reports of laryngeal adverse effects associated with VNS devices were identified and represented the eighth most common iatrogenic vagus nerve problem reported to the FDA. Laryngeal adverse effects included 78 reports of voice alteration and 57 reports of paresis/paralysis. The VNS device problems frequently associated with laryngeal adverse effects were high impedance (n = 15, 8.02%), incorrect frequency delivery (n = 10, 5.35%), and battery problems (n = 11, 5.88%). The number of laryngeal adverse effect reports per year peaked in 2012 with 43 cases. Conclusions and Relevance: This cross-sectional study found that although the literature demonstrates that vocal changes occur with nearly all VNS devices, the FDA receives adverse event reports of voice changes. Our results emphasize a potential need to improve patient counseling prior to VNS surgery to better set patient expectations regarding vocal changes and to prevent unnecessary patient concern. In addition, reports of vocal fold paresis/paralysis potentially suggest that patients may benefit from preoperative laryngeal assessment to differentiate preexisting vocal fold paralysis from that caused by VNS surgery.

Readmission Rates Following Major Head and Neck Surgery With Concurrent Tracheostomy.

OBJECTIVES: To determine the influence of major head and neck procedures on readmission and complication rates following tracheostomy. METHODS: A retrospective cohort study using the 2005 to 2017 National Surgical Quality Improvement Program (NSQIP) database. Current Procedural Terminology codes were used to identify tracheostomy patients and to define the underlying head and neck procedure. Patients under the age of 18 and with unknown pre-operative variables were excluded. Univariate and multivariable analyses were performed. RESULTS: A total of 3240 tracheostomy patients undergoing major head and neck surgery were identified in NSQIP. The 30-day mortality rate was 104 (3.2%) and 258 (9.0%) patients were readmitted. 637 (19.7%) patients had an unplanned return to the operating room. There were 1606 (49.6%) non-tracheostomy specific complications, which included 850 (26.2%) medical and 1142 (35.2%) surgical complications. On multivariable analysis, we found that the underlying procedures did not impact the risk of readmission (P > .05 for all). The underlying procedure was also not associated with unplanned return to the operating room except for thyroidectomies, which had a lower risk than free tissue graft reconstruction (OR = 0.53 (95%CI 0.31, 0.88), P = .018). CONCLUSION: While almost 1 in every 2 patients had a complication following major head and neck surgery that included creation of a tracheostomy, the rate of readmission is comparatively low and is not associated with the underlying procedure. These findings should reassure head and neck surgeons that properly managed tracheostomies do not constitute a disproportionate risk of readmission.

Cancer Risk Associated with Continuous Positive Airway Pressure: A National Study.

OBJECTIVE: In 2021 the U.S. FDA issued a Class 1 safety recall notice for specific devices due to a risk of carcinogen exposure. The objective of this study was to evaluate reports of cancer linked to CPAP devices to understand implications for the field of sleep medicine. METHODS: Cases of cancer involving CPAP devices were retrieved from the MAUDE database from 2014 to 2021 and analyzed with descriptive statistics. RESULTS: A total of 2571 patient injuries were associated with CPAP. Reports of cancer (n = 209; 4.62%) were the second most commonly documented patient problem associated with CPAP, although 1950 (43.13%) patients had a device problem without an associated injury. Of the 209 cancer cases associated with CPAP, 200 (95.7%) of the adverse event reports were received by the FDA in 2021. There were 174 (9.15%) descriptions of the CPAP polyurethane sound abatement foam degrading in association with a cancer diagnosis, but degradation was more commonly not associated with malignancy (n = 1728; 90.85%). Other frequently documented CPAP device problems included broken devices (n = 279; 6.92%), fire (n = 182; 4.51%), and patient-device incompatibility (n = 144; 3.57%). CONCLUSION: Malignancy associated with CPAP devices has been reported; however, future studies are required to establish causation. Given 95.7% of those documented cases were reported in 2021, otolaryngologists should be prepared to discuss the risks of carcinogenesis associated with CPAP. The otolaryngology community should also be aware of the potential bandwagon effect and the implications for CPAP compliance. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:2270-2274, 2022.

Association between hypertension requiring medication and 30-day outcomes in head and neck microvascular surgery.

BACKGROUND: Hypertension has been shown to be both a protective factor and a risk factor for complications in head and neck reconstructive surgery. METHODS: Retrospective analysis of microvascular free tissue transfer patients using the National Surgical Quality Improvement Program database. RESULTS: Hypertensive patients (n = 1598; 46.9%) had a significantly higher rate of complications, including pneumonia (p < 0.001), myocardial infarction (p = 0.003), and intra/post-operative transfusion (p < 0.001). In a multivariable model, hypertension was associated with returning to the operating room (OR = 1.45 [95% CI 1.20, 1.76], p < 0.001), post-operative medical complications (OR = 1.53 [95% CI 1.24, 1.90], p < 0.001), and surgical complications (OR = 1.17 [95% CI 1.00, 1.37], p = 0.047). However, no difference in 30-day readmission was found (p > 0.05). CONCLUSIONS: Hypertension is a modifiable risk factor for post-operative complications in head and neck free tissue transfer, in which prospective studies are required to establish causation. This study may serve as an impetus for proactive recommendations to manage hypertension before undergoing head and neck microvascular surgery.

Guideline - Adherence in advanced stage head and neck cancer is associated with improved survival - A National study.

OBJECTIVES: Understanding the prevalence of guideline non-adherence among patients with advanced head and neck cancer (HNC) and its impact on survival may facilitate increased adherence. Our objective was to perform a detailed analysis of overall National Comprehensive Care Network (NCCN) guideline adherence in a national cohort. METHODS: Using the National Cancer Database, we analyzed site-specific NCCN guideline adherence for treatment of 100,074 overall stage III and IVA HNC patients from 2004 to 2013. Main outcomes were guideline adherence rates and overall survival (OS). Adherence was categorized by treatment: surgery/ radiation. Reasons were categorized as: (1) high risk; (2) refusal; (3) not planned. RESULTS: After exclusion, the care of 25,620 patients was defined as non-adherent (25.6%), yet adherence rates significantly improved across the study's years. After multivariate analysis, non-adherence was associated with age ≥ 65, female gender, black race, comorbidity score ≥ 1, insurance status, clinical staging, primary site, and facility type. Patients not managed according to NCCN guidelines had a significantly reduced OS compared with patients treated on-guideline (hazard ratio (HR) = 1.51 (95 %CI 1.48-1.54), p < 0.001). 'Not planned' patients had reduced OS when compared to adherent patients (HR = 1.27 (95 %CI 1.23-1.30), p < 0.001). Off-guideline treated patients due to 'risk factors' had a decrease in overall survival (OS) compared with other reasons (p < 0.001 for all). CONCLUSIONS: Despite improvement over time, non-adherence to NCCN guidelines for advanced stage HNC remains high. Non-adherence is associated with decreased OS, regardless of the reason. Despite concerns from both patient and physician, efforts should be made to increase guideline awareness and adherence.

Risk Assessment in Thyroid Lobectomy and Total Thyroidectomy using Over 100 Thousand Cases.

OBJECTIVES: To assess risk factors and non-thyroid specific postoperative complications for thyroid lobectomy compared to total thyroidectomy. METHODS: A retrospective, cross-sectional study of adults undergoing a lobectomy or total thyroidectomy using the National Surgical Quality Improvement Program database between 2005 and 2017. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded. RESULTS: A total of 106 915 patients were analyzed, 64 763 total thyroidectomies and 42 152 lobectomies. Multivariable analysis demonstrated that total thyroidectomy patients were half as likely to return to the operating room (OR = 0.491 (95%CI 0.445-0.542), P < .001). Within this cohort, patients at greater risk for reoperation had a history of hypertension (OR = 1.225 (95%CI 1.090-1.376), P < .001), a malignant pathology (OR = 1.921 (95%CI 1.734-2.128), P < .001), and smoked (OR = 1.237 (95%CI 1.087-1.407), P = .001). Conversely, diabetes and body mass index did not impact the rate of reoperation when assessing total thyroidectomy and lobectomy. The most frequent non-thyroid specific complications in total thyroidectomy were unplanned intubation (0.5%), urinary tract infection (0.3%), and superficial surgical site infection (0.3%). In thyroid lobectomy, the most common complications were superficial surgical site infection (0.3%) and urinary tract infection (0.2%). CONCLUSIONS: Our multi-institutional study indicates specific risk factors for returning to the operating room that may warrant closer follow up after surgery for total thyroidectomy or thyroid lobectomy. We also identified the most common post-operative complications. During pre-operative planning, these findings should be considered by thyroid surgeons to help mitigate risk to patients.

A National Comparison of Postoperative Outcomes in Completion Thyroidectomy and Total Thyroidectomy.

OBJECTIVE: To characterize and assess the non-thyroid-specific postoperative complications of completion thyroidectomy as compared with total thyroidectomy. STUDY DESIGN: Retrospective analysis: 2005 to 2017. SETTING: National Surgical Quality Improvement Program database. SUBJECTS AND METHODS: Patients aged >18 years receiving a completion or total thyroidectomy were eligible for inclusion. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded. RESULTS: A total of 70,638 patients were analyzed, representing 64,763 total thyroidectomies and 5875 completion thyroidectomies. The 30-day mortality rate was 0.1% for both procedures (P > .05). Overall, 1.7% and 1.4% of patients undergoing total and completion thyroidectomies experienced at least 1 complication (P > .05), while 1.2% and 0.9% had a postoperative medical complication (P = .0186), respectively. On multivariable analysis, patients undergoing total thyroidectomies were significantly more likely to return to the operating room (odds ratio [OR], 1.36; 95% CI, 1.04-1.80; P = .027) and to be readmitted (OR, 1.45; 95% CI, 1.16-1.81; P = .001). Adjusted analysis also demonstrated that patients undergoing total thyroidectomies were more likely to be inpatients (OR, 1.17; 95% CI, 1.11-1.24; P < .001), be treated by nonotolaryngologists (OR, 1.36; 95% CI, 1.29-1.45; P < .001), and smoke (OR, 1.22; 95% CI, 1.13-1.33; P < .001). CONCLUSION: National data suggest that total and completion thyroidectomies are relatively safe procedures but that completion thyroidectomies are associated with lower rates of postoperative complications. These findings may play a role in determining treatment plans for patients and optimizing risk reduction.

Does neck dissection affect post-operative outcomes in parotidectomy? A national study.

OBJECTIVE: To characterize post-operative complications in parotidectomy with neck dissection. METHODS: Patients age ≥ 18 receiving a parotidectomy or parotidectomy with neck dissection between 2005 and 2017 were eligible for inclusion. Patients with unknown demographic variables were excluded. Univariate and multivariable logistic regression analyses were performed. RESULTS: A total of 13,609 parotidectomy patients were analyzed, 11,243 (82.6%) without neck dissection and 2366 (17.4%) with neck dissection. Both length of surgery (mean minutes ± standard deviation [SD] = 335.9 ± 189.2 vs. 152.9 ± 99.0, p < 0.001) and length of hospital stay (mean days ± SD = 3.90 ± 4.76 vs. 1.04 ± 2.14, p < 0.001) were greater with dissection. 13.9% of parotidectomies with neck dissection and 3.5% without dissection (p < 0.001) had at least one complication, which remained significant after multivariable adjustment (Odds Ratio[OR] = 1.565 (95%CI = 1.279-1.914), p < 0.001). The increase in post-operative complications was predominately driven by an increased transfusion rate (7.4% vs. 0.5%, p < 0.001). Multivariable analysis also demonstrated no significant difference in rates of returning to the operating room (OR = 1.122 (95%CI 0.843-1.493), p > 0.05) or rates of readmission (OR = 1.007 (95%CI 0.740-1.369), p > 0.05). Parotidectomy with neck dissection was more likely to be inpatient (OR = 4.411 (95%CI 3.887-5.004), p < 0.001) and to be ASA class 3 (OR = 1.367 (95%CI 1.194-1.564), p < 0.001). CONCLUSIONS: Nationwide data demonstrates that parotidectomy with neck dissection is associated with increased rates of post-operative complications; however, neck dissection did not significantly impact readmission or reoperation rates. These findings indicate that neck dissection is a relatively safe addition to parotidectomy and provide novel evidence in the management of parotid malignancies.

An Epidemiological Analysis and Comparison of Single Site and Multiple Site Fracture Repair: An NSQIP Analysis.

We aimed to utilize the 2010 to 2017 National Surgical Quality Improvement Program to evaluate the epidemiology and efficacy of facial fracture repairs, specifically comparing multiple fracture site repairs (MFR) compared to single fracture site repairs (SFR). Of 4739 patients, 718 (15.2%) were found to have undergone MFR. A total of 577 (80.4%) of the MFRs involved the midface only. A total of 2114 (52.6%) of the SFRs were mid-face fractures, while 1825 (45.4%) involved the lower-face and only 82 (2.0%) involved the upper-face. The most frequent MFR was combined orbital and malar/zygoma repair (230 cases [32.0%]). When comparing MFR and SFR of the mid-face, MFR patients were more commonly male, White, operated on by plastic surgeons, presented with contaminated wounds, and active smokers. While MFRs were associated with a longer operative time (P < 0.001) and a longer postoperative hospital stay (P < 0.001), there were no differences in reoperation or readmission. Overall, complication rates were low, but slightly higher in the mid-face MFR group (1.4% in mid-face SFR and 3.0% in mid-face MFR; P = 0.019). Sub-analysis of mid-face only MFRs and middle-lower-face MFRs revealed no difference in postoperative complication rates (3.0% and 7.0%, respectively; P = 0.071). The data presented suggests that MFR are a relatively common occurrence. Although plastic surgeons perform MFRs more frequently, it is currently unclear whether the underlying reason is a product of differences in training, coding patterns, or referral patterns. Though MFRs require more hospital resources, complications rates are low. This will help manage patient expectations and guide patient counseling before surgery, as well as help to plan postoperative care.

Single-Cell-Derived Primary Rectal Carcinoma Cell Lines Reflect Intratumor Heterogeneity Associated with Treatment Response.

PURPOSE: The standard treatment of patients with locally advanced rectal cancer consists of preoperative chemoradiotherapy (CRT) followed by surgery. However, the response of individual tumors to CRT is extremely diverse, presenting a clinical dilemma. This broad variability in treatment response is likely attributable to intratumor heterogeneity (ITH). EXPERIMENTAL DESIGN: We addressed the impact of ITH on response to CRT by establishing single-cell-derived cell lines (SCDCL) from a treatment-naïve rectal cancer biopsy after xenografting. RESULTS: Individual SCDCLs derived from the same tumor responded profoundly different to CRT in vitro. Clonal reconstruction of the tumor and derived cell lines based on whole-exome sequencing revealed nine separate clusters with distinct proportions in the SCDCLs. Missense mutations in SV2A and ZWINT were clonal in the resistant SCDCL, but not detected in the sensitive SCDCL. Single-cell genetic analysis by multiplex FISH revealed the expansion of a clone with a loss of PIK3CA in the resistant SCDCL. Gene expression profiling by tRNA-sequencing identified the activation of the Wnt, Akt, and Hedgehog signaling pathways in the resistant SCDCLs. Wnt pathway activation in the resistant SCDCLs was confirmed using a reporter assay. CONCLUSIONS: Our model system of patient-derived SCDCLs provides evidence for the critical role of ITH for treatment response in patients with rectal cancer and shows that distinct genetic aberration profiles are associated with treatment response. We identified specific pathways as the molecular basis of treatment response of individual clones, which could be targeted in resistant subclones of a heterogenous tumor.

Industry Payments for Otolaryngology Research: A Four-Year Analysis of the Open Payments Database.

OBJECTIVE: To characterize industry research payments to otolaryngologists. STUDY DESIGN: Cross-sectional retrospective analysis. METHODS: We examined research payments made to otolaryngologists 2014 through 2017 included in the Open Payments Database. Trends in payment values over time were characterized and compared to other surgical specialties. Geographical and temporal trends in payments to specific principal investigators, along with the ties to specific companies, were analyzed. RESULTS: Among surgical specialties, otolaryngology was the second lowest paid in terms of total compensation from industry for research per active U.S. physician. The median (mean) payment to otolaryngologists was $819 ($5,514), $548 ($3,083), $771 ($3,484), and $1,000 ($5,768) in 2014, 2015, 2016, and 2017, respectively. There was typically a higher mean and median payment per otolaryngologists in the Northeast, although significant differences between each region varied by year. The 40 most highly funded recipients had total compensation that was on average spread over 3.35 years of the database, 2.975 different companies, and 7.35 distinct scientific studies-all significantly higher compared to otolaryngologists with less funding. CONCLUSION: Research payments to otolaryngologists are concentrated in a small number of otolaryngologists; however, many of the most highly funded principal investigators worked on numerous studies with a variety of different companies over many years. Our characterization of the Open Payments Database over 4 years illustrates the depth of relationship between otolaryngology research and industry as well as raises awareness regarding the ease of connecting otolaryngologists to research payments. LEVEL OF EVIDENCE: NA Laryngoscope, 130:314-320, 2020.

Is robotic surgery an option for early T-stage laryngeal cancer? Early nationwide results.

OBJECTIVES/HYPOTHESIS: To characterize patients undergoing laryngeal transoral robotic surgery (TORS) and compare to open partial surgery and transoral laser microsurgery (TLM) in achieving negative margins, requiring adjuvant radiation, and overall survival. STUDY DESIGN: Retrospective database analysis. METHODS: Early-stage (T1/2) laryngeal squamous cell carcinoma patients from the National Cancer Database. Univariable and multivariable logistic and Cox regressions were used to identify predictors. RESULTS: There were 1,780 patients included in the study (186 [10.4%] = TORS; 523 [29.4%] = open surgery; 1,071 [60.2%] = TLM). TORS was more commonly treated at academic centers (68.8% = open surgery, 53.9% = TLM, 71.0% = TORS; P < .001) and had more T2 (52.7% = TORS, 46.7% = open surgery, 20.5% = TLM; P < .001) and N-positive disease (26.9% = TORS, 19.5% = open surgery, 5.5% = TLM; P < .001). Surgical approach was significantly associated with margin status (positive margin rates: TORS = 17.4%, TLM = 20.0%, open surgery = 13.8%) between open surgery and TLM in multivariable analysis (compared to open surgery, TLM: 1.63 [1.12-2.38], TORS: 1.18 [0.72-1.94]; P = .04). Surgical approach was not associated with receipt of adjuvant radiation (compared to open surgery, TLM: 1.52 [1.04-2.24], TORS: 1.56 [0.97-2.49]; P = .05). It was not associated with margins or adjuvant radiation in supraglottic patients. TORS had the highest 5-year overall survival, although the survival for TLM was similar (68.7% and 64.8%, respectively), and both were higher than that of open surgery (59.1%; P = .01). In multivariable Cox regression for supraglottic patients, there was no observed difference between TORS and open surgery (compared to TORS, open surgery: 1.44 [0.93-2.24]; P = .25). CONCLUSIONS: On multivariable analysis, there was no observed difference in margin status in TORS patients compared to TLM and open surgery (in both the total cohort and supraglottic subgroup). Similarly there was no observed difference in necessitating adjuvant radiation. In Cox regression, there was no observed difference between TORS and open surgery in overall survival for supraglottic patients. This study suggests that TORS may be a viable treatment option for early-stage laryngeal cancer. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1195-1201, 2020.

Cells deficient for Krüppel-like factor 4 exhibit mitochondrial dysfunction and impaired mitophagy.

Krüppel-like factor 4 (Human Protein: KLF4; Human Gene: Klf4; Murine Protein: KLF4; Murine Gene: Klf4) is a zinc finger-containing transcription factor with diverse regulatory functions. Mouse embryonic fibroblasts (MEFs) lacking Klf4 exhibit genomic instability, increased reactive oxygen species (ROS), and decreased autophagy. Elevated ROS is linked to impairments in mitochondrial damage recovery responses and is often tied to disruption in mitochondrial-targeted autophagy known as mitophagy. In this study, we sought to identify a mechanistic connection between KLF4 and mitophagy. Using flow cytometry, we found that Klf4-null MEFs have diminished ability to recover mitochondrial health and regulate ROS levels after mitochondrial damage. Confocal microscopy indicated decreased localization of autophagy protein LC3 to mitochondria following mitochondrial damage in Klf4-null cells, suggesting decreased mitophagy. Western blotting and RT-PCR revealed decreased mRNA and protein expression of the mitophagy-associated protein Bnip3 and antioxidant protein GSTα4 in Klf4-null cells, providing a rationale for their impaired mitophagy and ROS accumulation. Inducing Bnip3 expression in these cells recovered mitophagy but did not decrease ROS accumulation. Our findings suggest that in Klf4-null cells, decreased Bnip3 expression impairs mitophagy and is associated with increased mitochondrial ROS production after mitochondrial damage, providing a rationale for their genomic instability and supports a tumor suppressive role for KLF4 in certain tumors as previously observed.

Margins in Laryngeal Squamous Cell Carcinoma Treated with Transoral Laser Microsurgery: A National Database Study.

OBJECTIVES: To determine national positive margin rates in transoral laser microsurgery, to compare patients with positive and negative margins, and to identify factors associated with positive margins. STUDY DESIGN: Retrospective review of the National Cancer Database. SETTING: Population based. SUBJECTS/METHODS: Patients included those with TIS-T3 laryngeal squamous cell carcinoma (2004-2014). Univariable and multivariable logistic regression were used to identify predictors. RESULTS: A total of 1959 patients met inclusion criteria. The national positive margin rate was 22.3%. Sixty-five percent of patients had T1 disease; 94.3% were N-negative; and 74.0% had glottic tumors. Fifty-eight percent of patients were treated at academic centers, and 60.6% were treated at facilities performing <2 cases per year. On multivariable analysis, factors associated with margin status included facility volume (odds ratio [95% CI]; in cases per year: 0.93 [0.89-0.97], P = .001), academic status (vs nonacademic; academic: 0.70 [0.54-0.90], P = .008), T-stage (vs T1; T2: 2.74 [2.05-3.65], T3: 5.53 [3.55-8.63], TIS: 0.59 [0.38-0.92], P < .001), and N-stage (vs N0; N1: 3.42 [1.79-6.54], N2: 2.01 [1.09-3.69], P < .001). Tumor subsite was not associated with margin status. CONCLUSION: The national positive margin rate for laryngeal laser surgery is 22%, which is concerning given the equivalent survival benefit offered by surgery and primary radiation and the increased likelihood of bimodal therapy in the situation of positive margins. Cases treated at nonacademic centers and those with lower caseloads had a higher likelihood of positive margins. There was a linear association between T-stage and likelihood of positive margins, with T3 tumors being 5 times as likely as T1 to yield positive margins. This study highlights the importance of proper patient selection for transoral laser microsurgery resections.

Epidemiological analysis of croup in the emergency department using two national datasets.

OBJECTIVES: To characterize cases of croup presenting to emergency departments (EDs) nationwide, analyze trends, and determine readmission rates. METHODS: Retrospective review of the Nationwide Emergency Department Sample (2007-2014) and the National Hospital Ambulatory Medical Care Survey (2008-2015). RESULTS: Both databases provided similar descriptive statistics. Annual mean of 352,388 (weighted) cases in the National Emergency Department Sample (1.35% of ED cases). Average age and male:female ratio 2.50 years and 1.95:1, respectively. Peak incidence was in autumn (October = 13.7%) with troughs in the summer (July = 3.7%). 21.3% received nebulizers, <1% laryngoscopic or airway procedures, 75.1% steroids, and 13.3% antibiotics. Of the patients receiving antibiotics, 16.0% had isolated croup. 3.0% of cases were admitted to the hospital. No trend was identified in the incidence of croup, mean age, or antibiotic and steroid usage. Hospital admission rates decreased (4.0%-2.3%) and nebulizer usage increased (14.6%-27.5%; p < 0.05). 5% of patients represented repeat admissions (were seen within 72 h prior). CONCLUSIONS: Croup imposes a significant burden on the ED. Although hospital admissions decreased, annual incidence in the ED remained stable. The majority of cases are in males less than three years old, and 5.0% of patients represented readmissions. Only three-quarters received glucocorticoids despite the proven benefits, including reducing readmission rates. Antibiotic usage was high, with a large number representing potential cases of inappropriate antibiotic use.

A comparison of benign positional vertigo and stroke patients presenting to the emergency department with vertigo or dizziness.

PURPOSE: To compare imaging utilization between patients presenting to the emergency department (ED) with vertigo and dizziness (VDS) who are diagnosed with stroke and benign paroxysmal positional vertigo (BPPV). METHODS: All patients presenting to the ED with VDS (January 2014-June 2018) were identified. Those with a discharge diagnosis of stroke and BPPV were analyzed. RESULTS: 17,884 patients presented to with VDS. 452 were diagnosed with BPPV and 174 with acute stroke. 55.7% of stroke patients had at least one neurologic symptom beyond VDS, 63.8% had a positive neurologic exam, and 80.5% had either; 90.2% had at least one stroke risk factor (RF). 42.0% of BPPV patients received imaging, of which 24.7% had neurologic symptoms beyond VDS, 16.3% had neurologic exam findings, and 34.2% had either (P < 0.001, as compared to stroke). 43 patients (22.6%) lacked neurologic symptoms, exam findings, and stroke RFs; 40 had an adequate HINTS (head impulse, nystagmus, skew) exam. The most common imaging modality received by BPPV patients was plain CT Head (54.2%), followed by CT/CTA (43.7%), and MRI brain (26.3%). CT head was the initial imaging of choice in 44.7% and CT/CTA in 42.6%. CONCLUSIONS: Imaging utilization in BPPV patients presenting with VDS is high. The profile of patients with BPPV that received imaging was substantially more benign than that of stroke patients (a quarter had no neurologic symptoms, exam findings, or stroke RFs). The HINTS exam was underutilized, and computed tomography was heavily utilized despite well-established limitations in diagnosing posterior circulation strokes. This study highlights the need for increased training in the HINTS exam, narrowing of the scope for computed tomography, and a higher threshold for imaging patients with isolated VDS.

Positive margin rates and predictors in transoral robotic surgery after federal approval: A national quality study.

BACKGROUND: Purpose of the study is to assess nationwide margin performance in oropharynx transoral robotic surgery (TORS). METHODS: Retrospective review of the National Cancer Database. RESULTS: Two thousand six hundred sixty-one patients were included. The national positive margin rate (PMR) was 16.9%. High-volume facilities had a lower PMR than low-volume facilities (12.7% vs 21.9%; P < .001). Patients with disease of the tonsil had a lower PMR (15.7%) than base-of-the-tongue (18.2%; P = .14). PMR increased with T classification (T1 = 13.0%, T2 = 17.1%, T3 = 28.2%, T4a = 45.9%, T4b = 58.3%; P < .001). On multivariable regression, factors associated with margin status included only lymph-vascular invasion (1.63[1.13-2.36]; P = .01), high volume (0.57[0.36-0.92]; P = .005), and T classification (as compared to T1, T2: 1.50[1.03-2.18], T3: 3.11[1.77-5.46], T4a: 7.03[2.95-16.75], T4b: 6.72[1.26-35.93]; P < .001). CONCLUSIONS: National PMR is 16.9%, substantially higher than reported in high-volume TORS centers. There is a linear association between positive margins and T classification, with T3 and T4 PMRs exceeding 28%. High-volume facilities are half as likely to yield positive margins compared to low-volume facilities. There was no association between human papilloma virus status, tumor subsite, or academic facility status and positive margins.