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Objective: As the incidence of human papillomavirus related oropharyngeal cancer continues to rise, it is increasingly important for public understanding to keep pace. This study aimed to identify areas of patient interest and concern regarding human papillomavirus and oropharyngeal cancer. Method: This study was a retrospective survey of search queries containing the keywords 'HPV cancer' between September 2015 and March 2021. Results: There was 3.5-fold more interest in human papillomavirus related oropharyngeal cancer (15 800 searches per month) compared with human papillomavirus related cervical cancer (4500 searches per month). Among searches referencing cancer appearance, 96.8 per cent pertained to the head and neck region (3050 searches per month). Among vaccination searches, 16 of 47 (34.0 per cent; 600 searches per month) referenced human papillomavirus vaccines as being a cause of cancer rather than preventing cancer. Conclusion: The vast majority of online searches into human papillomavirus cancer pertain to the oropharynx. There are relatively few search queries on the topic of vaccination preventing human papillomavirus associated oropharyngeal cancer, which highlights the continued importance of patient education and awareness campaigns. [ABSTRACT FROM AUTHOR]

Background: Delays in the diagnosis and therapy of benign paroxysmal positional vertigo can greatly impact quality of life and increase healthcare costs for patients. This study aimed to appraise the quality of clinical practice guidelines for the diagnosis and management of benign paroxysmal positional vertigo. Methods: A comprehensive database search of clinical practice guidelines was completed up to 30 October 2021. Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation II instrument in the quality appraisal. Results: The highest score was in 'clarity and presentation' (58.33 ± 22.7). The lowest score was in 'applicability' (13.96 ± 30.1). Overall, four clinical practice guidelines were 'low quality' and only one guideline was 'high quality'. Conclusion: This review identified a significant lack of quality in clinical practice guideline development for benign paroxysmal positional vertigo, highlighting the need for a more rigorous approach for future guideline development. [ABSTRACT FROM AUTHOR]

Background: Vessel grafting is an important technique in head and neck free tissue transfer (FTT) reconstruction when a tension-free anastomosis is not otherwise feasible. To our knowledge, there are limited data regarding interposition artery grafts for arterial anastomoses in head and neck reconstruction. Here, we present a multi-institutional cohort of arterial interposition grafts for FTT reconstruction for head and neck defects., Methods: A retrospective review was conducted at four tertiary care institutions for patients who underwent FTT reconstruction for head and neck defects which utilized an interposition artery graft for the arterial anastomosis. Charts were reviewed for type and length of artery grafts harvested, surgical indication, indication for artery graft, types of flaps harvested, and various preoperative characteristics (including history of radiation or previous FTT reconstruction surgery). Postoperative complications within postoperative day 30 were measured and reported., Results: Nine patients met inclusion criteria. The lateral circumflex femoral artery (either transverse or descending branches) (n = 3) and facial artery (n = 3) were the most commonly harvested arteries. The scalp (n = 5) was the most common primary defect site. Seven grafts were harvested initially and in a planned fashion, while two were harvested as salvage techniques (either for flap salvage or vein graft failure). In planned grafts, arteries were the preferred interposition grafting method due to either size match preferences (n = 4) or similarities in wall thickness (n = 3) between graft and recipient artery. There were no reported cases of unplanned readmission, postoperative hematoma, fistula formation, wound infection, or donor site morbidities. Two patients required unplanned return to the operating room for flap compromise, both of which ultimately resulted in flap failure secondary to clot formation at both arterial and venous anastomoses., Conclusions: When arterial pedicle length is insufficient, interposition artery grafting is both a feasible and viable technique to achieve tension-free arterial anastomoses for select cases of highly complex head and neck free tissue reconstruction., (© 2024 Wiley Periodicals LLC.)

Objective: To characterize the estimated prevalence and clinicodemographic features of Ménière's disease (MD) using current diagnostic criteria., Methods: A cross-sectional study was undertaken at our tertiary academic referral center. All patients seen in Otolaryngology clinic with ICD-10 diagnoses of MD, from January 1, 2013 to July 31, 2022 were identified. Chart review was undertaken to determine the estimated prevalence of MD meeting AAO-HNS diagnostic criteria. Clinicodemographic features were evaluated against a comparator group without MD seen in our health system., Results: Of 806 ICD-10 diagnoses of MD, we identified 480 MD cases meeting diagnostic criteria (168 definite). Mean age at presentation for MD cases was 49 years. Forty-seven percent of cases were male. A significantly higher proportion of MD cases than comparators were white (76% vs. 66%, p < 0.001). Mean time since MD symptom onset was 6.7 years, with a mean attack duration of 4.6 h; 7.5% of MD cases reported a positive family history, and 7% had bilateral disease. The odds of reporting migraine were significantly greater among MD patients than comparators (OR 1.74 [1.26-2.42]); the odds of having autoimmune conditions were lower (OR 0.45 [0.28-0.74]); and the odds of reporting allergies were no different (OR 0.96 [0.74-1.25]) versus comparator patients after controlling for demographic characteristics., Conclusions: Among MD diagnoses, there is a low estimated prevalence of MD meeting diagnostic criteria, and an even lower prevalence of definite MD. Compared to a comparator group of patients seen for any disorder, patients with MD are more likely to be white, male, and have a history of migraine., Level of Evidence: 4 Laryngoscope, 134:3310-3315, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Several clinical practice guidelines (CPGs) have been produced to optimize the diagnosis and management of pediatric foreign body aspiration and ingestion. However, to date there have been no critical evaluations of their methodological rigor or quality. Herein, we address this need via the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument., Methods: A literature search of Embase, MEDLINE via PubMed, and Scopus was performed up until February 25, 2021. Identified CPGs were then assessed by four independent reviewers trained in AGREE II. A scaled domain score of >60% was indicated as satisfactory quality. Intraclass correlation coefficients (ICC) were calculated to assess inter-reviewer agreement., Results: 11 guidelines were assessed with only one being classified as high quality and others being either average (two) or low quality (eight). Domain 4 (clarity of presentation) achieved the highest mean score (66.41 ± 13.33%), while domain 5 (applicability) achieved the lowest score (10.80 ± 10.37%). ICC analysis revealed generally strong agreement between reviewers with a range of 0.60-0.98., Conclusion: Quality appraisal using the AGREE II instrument suggests that the methodologic rigor and quality of current guidelines for the diagnosis and management of pediatric foreign body aspiration and ingestion need significant improvement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To date, no study provides a comprehensive analysis of traumatic orbital floor fractures across the United States. We aimed to characterize patient demographics, injury-related variables, and operative management in this population., Method: The National Trauma Data Bank was queried for open or closed orbital floor fractures from 2008 to 2016. Clinical data were extracted., Results: Overall, 148,592 orbital floor fractures were identified, with 142,577 (95.9%) closed- and 6158 (4.1%) open-type fractures. A total of 106,243 (71.5%) patients were male and the median patient age was 41 years. The majority of patients (79.2%) had abbreviated injury scale scores of ≤2, indicating minor/moderate injury. Fracture mechanism of injury (MOI) differed by gender, with the most frequent being unarmed fights in men (34.3%) and falls in women (14.0%). There were 29,600 patients (19.9%) with isolated orbital floor (I-OF) fractures. The MOI most strongly associated with operative intervention of with I-OF fractures were penetrating injuries caused by a firearm ( odds ratio [OR]: 2.91; 95% confidence interval [ CI ]: 1.62-5.20) and cuttings/piercings ( OR : 2.17; 95% CI : 1.29-3.65)., Conclusion: This large epidemiological study reveals that orbital floor fractures tend to present with minor or moderate injuries and are more likely to require operative intervention in setting of firearm or cut/pierce injuries., Competing Interests: Professor Karthik Rajasekaran is a member of World Journal of Otorhinolaryngology—Head & Neck Surgery (WJOHNS) editorial board and is not involved in the peer review process of this article. The authors declare no conflicts of interest., (© 2024 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons, Ltd on behalf of Chinese Medical Association.)

Objective: To review the literature and our institutional experience regarding the risk of meningitis in patients with spontaneous lateral skull base cerebrospinal fluid (sCSF) leaks awaiting surgical repair, and the roles of antibiotic prophylaxis and pneumococcal vaccination, if known., Methods: A retrospective chart review and systematic review of the literature was undertaken to identify the incidence of meningitis in patients with sCSF leaks awaiting surgical repair. Adults managed surgically for sCSF leaks at an academic tertiary care center over a 10-year period were included. Data was collected on receipt of prophylactic antibiotics and/or pneumococcal vaccines during the timeframe between diagnosis and surgical repair., Results: Institutional review identified 87 patients who underwent surgical repair of spontaneous leaks, with a 0% incidence of meningitis over a median duration of 2 months while awaiting surgery (mean 5.5 months, range 0.5-118 months). Eighty-eight percent of patients did not receive prophylactic antibiotics. No studies in the published literature demonstrated the impact of prophylactic antibiotics or pneumococcal vaccine on meningitis risk., Conclusions: There appears to be a low risk of meningitis among patients with lateral skull base sCSF leaks awaiting surgery for short durations (≤2 months), even in the absence of prophylactic antibiotics. There is a substantial gap in the published literature assessing the risk of meningitis and roles of antibiotics and vaccination in this patient population, indicating the need for large-scale study to conclusively elucidate the nature of this risk., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To determine whether gender differences exist in the training history, practice patterns, and home lives of surgeons who perform microvascular reconstruction of the head and neck., Study Design: Cross-sectional survey., Setting: Medical facilities that employ surgeons who practice head and neck microvascular reconstruction in the United States., Methods: A survey was created using the Research Electronic Data Capture Framework and was distributed via email to microvascular reconstructive surgeons. Descriptive statistics were performed using Stata software., Results: No significant differences were found in training or current practice patterns between microvascular surgeons who identify as men versus those who identify as women. Women had fewer children (p = .020) and were more likely to be childless (p = .002). Whereas men were more likely to report a spouse/partner as primary caretaker, women were more likely to hire a professional caretaker or cite themselves as a primary caretaker (p < .001). Women were more likely to have finished residency (p = .015) and fellowship (p = .014) more recently and to practice in the Southeast (p = .006). Of the microvascular surgeons who reported practice setting switches, men more commonly changed positions for career advancement, whereas women were more likely to switch due to burnout (p = .002)., Conclusion: This study found no gender-based differences in training or practice patterns. However, significant differences were identified in childbearing, family structure, geographic practice location, and motives for switching practice., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Importance: Olfactory dysfunction (OD) is increasingly recognized as a robust marker of frailty and mortality. Despite broad recognition of frailty as a critical component of head and neck cancer (HNC) care, there is no standardized frailty assessment., Objective: To assess the prevalence of OD and its association with frailty and postoperative outcomes in HNC., Design, Setting, and Participants: In this prospective cohort study with enrollment between February 17, 2021, to September 29, 2021, at a tertiary academic medical center, 85 eligible adult patients with primary, treatment-naive HNC of mucosal or cutaneous origin were included. Patients with a history of COVID-19, neurocognitive, or primary smell/taste disorders were excluded., Exposures: Prospective olfactory assessments (self-reported, visual analog scale [VAS] and psychophysical, University of Pennsylvania Smell Identification Test [UPSIT]) with concurrent frailty assessment (Risk Analysis Index [RAI]) were used. Olfactory-specific quality of life (QOL) was examined with brief Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS)., Main Outcome(s) and Measure(s): The primary outcome was the prevalence of OD as assessed by VAS (0-10, no to normal smell) and UPSIT (0-40, higher scores reflect better olfaction) and its association with frailty (RAI, 0-81, higher scores indicate greater frailty). For surgical patients, secondary outcomes were associations between OD and postoperative length of stay (LOS), 30-day postoperative outcomes, and QOD-NS (0-21, higher scores indicate worse QOL)., Results: Among 51 patients with HNC (mean [SD] age, 63 [10] years; 39 [77%] male participants; 41 [80%] White participants), 24 (47%) were frail, and 4 (8%) were very frail. Despite median (IQR) self-reported olfaction by VAS of 9 (8-10), 30 (59%) patients demonstrated measured OD with psychophysical testing. No meaningful association was found between self-reported and psychophysical testing (Hodges-Lehmann, <0.001; 95% CI, -2 to 1); a total of 46 (90%) patients did not report decreased olfaction-specific QOL. Median UPSIT scores were lower in frail patients (Hodges-Lehmann, 6; 95% CI, 2-12). Multivariate modeling demonstrated severe microsmia/anosmia was associated with 1.75 (95% CI, 1.09-2.80) times odds of being frail/very frail and approximately 3 days increased LOS (β, 2.96; 95% CI, 0.29-5.62)., Conclusions and Relevance: Although patients with HNC are unaware of olfactory changes, OD is common and may serve as a bellwether of frailty. In this prospective cohort study, a dose-dependent association was demonstrated between increasing degrees of OD and frailty, and the potential utility of olfaction was highlighted as a touchstone in the assessment of HNC frailty.

Objectives: Thyroidectomy is among the most commonly performed head and neck surgeries, however, limited existing information is available on topics of interest and concern to patients., Study Design: Observational., Setting: Online., Methods: A search engine optimization tool was utilized to extract metadata on Google-suggested questions that "People Also Ask" (PAA) pertaining to "thyroidectomy" and "thyroid surgery." These questions were categorized by Rothwell criteria and topics of interest. The Journal of the American Medical Association (JAMA) benchmark criteria enabled quality assessment., Results: A total of 250 PAA questions were analyzed. Future-oriented PAA questions describing what to expect during and after the surgery on topics such as postoperative management, risks or complications of surgery, and technical details were significantly less popular among the "thyroid surgery" group ( P  < 0.001, P  = 0.005, and P  < 0.001, respectively). PAA questions about scarring and hypocalcemia were nearly threefold more popular than those related to pain (335 and 319 vs. 113 combined search engine response page count, respectively). The overall JAMA quality score remained low (2.50 ± 1.07), despite an increasing number of patients searching for "thyroidectomy" ( r (77) = 0.30, P  = 0.007)., Conclusions: Patients searching for the nonspecific term "thyroid surgery" received a curated collection of PAA questions that were significantly less likely to educate them on what to expect during and after surgery, as compared to patients with higher health literacy who search with the term "thyroidectomy." This suggests that the content of PAA questions differs based on the presumed health literacy of the internet user., Competing Interests: Professor Karthik Rajasekaran is a member of World Journal of Otorhinolaryngology – Head & Neck Surgery (WJOHNS) editorial board and is not involved in the peer review process of this article. The other authors declare no conflict of interest., (© 2023 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

Objective: Cerebrospinal fluid (CSF) leaks are a complication from dural violations that can occur in the setting of skull base fractures. No prior study provides a nationwide epidemiological analysis of traumatic CSF leaks. The objective of this report is to characterize patient demographics, injury-related variables, and operative management., Methods: The national trauma data bank was queried for both anterior and lateral skull base fracture cases between 2008 and 2016. Clinical data were extracted., Results: A total of 242 skull base fractures with CSF leak were identified. Most patients were male (84.3%), and the median patient age was 39.7±17.6 years old. Glasgow Coma Scale was 14.0 [interquartile range (IQR): 6.5-10.6] for lateral fractures, 13.0 (IQR: 3.0-10.0) for anterior fractures, and severe range for combined fractures at 7.0 (IQR: 5.0-9.0) (analysis of variance, P =0.122). Common mechanisms of injury were motor vehicle accidents (107, 44.2%), followed by falls and firearms (65, 26.9% and 20, 8.3%, respectively). The median length of stay was 2 weeks, with a median of 14 days (IQR: 10-25) for the anterior fractures and 10 days (IQR 5-19) among the lateral fractures ( P =0.592). Patients were most commonly discharged home in both the anterior (43.8%) and lateral (49.2%) groups., Conclusions: The prototypical patient tends to be a young adult male presenting with moderate-to-severe range neurological dysfunction after a vehicular accident. The overall prognosis of skull base fractures with CSF leak remains encouraging, with nearly half of these patients being discharged home within 2 weeks., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Objective: Evaluate the feasibility and cost-effectiveness of telehealth head and neck cancer (HNC) survivorship care., Data Sources: Ovid MEDLINE, Embase, Scopus, CINAHL., Review Methods: A systematic search for peer-reviewed feasibility studies on telehealth models for HNC survivorship care published between 2005 and 2021 was conducted using the terms "head and neck cancer" and "telehealth" and their synonyms. Inclusion criteria were studies on telehealth survivorship program interventions for HNC patients with quantitative feasibility outcome measures (eg, enrollment, retention, attrition/dropout rate, adherence/task completion rate, patient satisfaction, cost)., Results: Thirty-eight studies out of 1557 identified met inclusion criteria and were included for analysis. Feasibility outcomes evaluated were enrollment and attrition rates, adherence/task completion rates, patient satisfaction, and user feedback surveys in different survivorship domains. Patient enrollment ranged from 20.8% to 85.7%, while attrition ranged from 7% to 47.7%. Overall, adherence was 30.2% higher in the intervention group than in the control group (46.8% vs 16.6%). Studies with cost analysis found telehealth models of care to be statistically significantly less expensive and more cost-efficient than the standard model of care, with a $642.30 saving per patient (n = 3). Telehealth models also substantially reduced work time saving per visit (on average, 7 days per visit)., Conclusion: While telehealth survivorship programs are feasible and cost-effective and are associated with improved patient outcomes, they might not be ideal for every patient. Further investigations are needed to understand the role of telehealth in survivorship care, given the variability in study design, reporting, measures, and methodological quality., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objective: To assess existing literature on topical intranasal fluorescein (TINF) for the diagnosis and localization of nasal cerebrospinal fluid (CSF)., Study Design: Systematic review., Methods: A 6-database literature search was conducted to identify articles providing insight into TINF for the diagnosis and treatment of sinonasal CSF leak. Demographic characteristics, technical details, efficacy, and safety data were extracted and analyzed. Methodological quality was assessed using Methodological Items for Non-Randomized Studies (MINORS) criteria., Results: All studies reported a diagnostic accuracy rate ≥96%. There were no major complications reported for any patient (n=99) with either 5% or 10% fluorescein use. The MINORS instrument of methodological quality indicated that the assessed studies were of moderate quality (7.29 out of a maximum score of 24)., Conclusion: This systematic review indicates that TINF is an easy, safe, inexpensive, and sensitive approach for the diagnosis and treatment of sinonasal CSF leakage. For these reasons, it may be especially well suited for resource-limited clinical scenarios., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Background: Head and neck free flap survival relies on adequate tissue perfusion from the external carotid artery (ECA), and vessel length is inversely proportional to blood flow rate. Objective: Investigate whether distance from the ECA (as a proxy for pedicle vessel length) predicts flap survival or complications. Methods: Retrospective review of free flaps performed at three academic centers from 9/2006 to 8/2021. Flaps were categorized by distance from the ECA: orbit and above (zone 1), maxilla to parotid (zone 2), and mandible and below (zone 3). Secondary analysis assessed flap outcomes stratified by average historical pedicle length. Results: A total of 2,369 flaps were identified in zones 1 ( n  = 109), 2 ( n  = 1878), and 3 ( n  = 382). Rates of flap failure (4.9%) and perioperative complications (36.3%) did not differ by zone or pedicle length. Zone 3 flaps, most commonly located in the larynx and hypopharynx, had significantly higher rates of fistula and infection. Conversely, 30-day readmission rates were significantly lower in patients with zone 2 flaps ( p  < 0.001). Rates of all other complications did not differ significantly between zones. Conclusions: Proximity to mucosal anatomic sites was a more powerful predictor of free flap viability than pedicle length or ECA proximity.

Objectives: To determine whether 2 different methods of post-operative head and neck free flap monitoring affect flap failure and complication rates., Methods: A retrospective chart review of 803 free flaps performed for head and neck reconstruction by the same microvascular surgeon between July 2013 and July 2020 at 2 separate hospitals within the same healthcare system. Four-hundred ten free flaps (51%) were performed at Hospital A, a medical center where flap checks were performed at frequent, scheduled intervals by in-house resident physicians and nurses; 393 free flaps (49%) were performed at Hospital B, a medical center where flap checks were performed regularly by nursing staff with resident physician evaluation as needed. Total free flap failure, partial free flap failure, and complications (consisting of wound infection, fistula, and reoperation within 1 month) were assessed., Results: There were no significant differences between Hospitals A and B when comparing rates of total free flap failure, partial free flap failure, complication, or re-operation ( P  = .27, P  = .66, P  = .65, P  = .29, respectively). There were no significant differences in urgent re-operation rates for flap compromise secondary to thrombosis and hematoma ( P  = .54)., Conclusions: In our series, free flap outcomes did not vary based on the degree of flap monitoring by resident physicians. This data supports the ability of a high-volume, well-trained, nursing-led flap monitoring program to detect flap compromise in an efficient fashion while limiting resident physician obligations in the age of resident duty hour restrictions.

Malpractice claims involving robot-assisted surgical procedures have increased more than 250% in the past 7 years compared to the seven years prior. We examined robotic surgery malpractice claims to identify trends in claimed liabilities, describe legal outcomes, and determine strategies to minimize future litigation. The Westlaw legal database was queried retrospectively for U.S. state and federal trials regarding robot-assisted surgical procedures from 2006 to 2013 and 2014 to 2021. Data abstracted from verdict reports included year, state, court type, defendant specialty, procedure performed, claimed injuries and liabilities, verdict, and damage amount awarded. Sixty-one cases across 25 states were identified, 16 cases between 2006 and 2013, and 45 from 2014 to 2021. Among those 45 cases, defendant verdicts predominated (n = 35, 77.8%), with only four plaintiff verdicts (8.9%) and six settlements (13.3%). Overall, 169 liabilities were claimed, most commonly negligent surgery (82.2%), misdiagnosis/failure to diagnose (46.7%), delayed treatment (35.6%), and lack of informed consent (31.1%). Thirteen cases resulted in indemnity payments (mean = $1,251,274), with damages ranging from $10,087 (infection and retained foreign body) to $5,008,922 (patient death). Hysterectomy (n = 19, 42.2%) was the most commonly litigated surgery, followed by prostatectomy (n = 5) and hernia repair (n = 4). The most litigated specialties were obstetrics/gynecology (48.9%), general surgery (28.9%), and urology (15.6%). Malpractice litigation in robot-assisted surgery is infrequent. As robotic procedures become more commonplace, surgeons must keep common liabilities in mind, as there are valuable and actionable lessons to be learned from these cases. Malpractice reform, continuing medical education activities, and improved informed consent protocols may help minimize future litigation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Purpose: Recurrent head and neck cancer (HNC) has a significant global disease burden and its treatment is complex. Multiple clinical practice guidelines (CPGs) have been developed to improve management of these patient populations; however, no study has systematically reviewed the quality and rigor in development of these guidelines. Here, we identify and systematically appraise existing recommendations for the management of recurrent HNC and assess their clinical applicability, methodologic rigor, and transparency of development., Methods: A systematic search of the PubMed, Embase, and Scopus databases was conducted for recurrent HNC CPGs. Each guideline was scored independently by four reviewers trained in the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II) methodology. Salient recommendations from the selected guidelines were summarized., Results: Our literature search yielded 1799 articles; after iterative title/abstract and full text screening, five remaining guidelines met inclusion criteria. CPGs received the lowest scores in 'Applicability' and 'Rigor of development,' with scores of 12.9% and 22.3%, respectively. Overall quality of available guidelines for management of recurrent HNC is poor, with an average overall scaled domain score of 40.9% (± 11.0), and with four guidelines (80.0%) receiving an overall quality rating of 'low'., Conclusion: We found significant variability in quality and overall lack of methodologic rigor among available guidelines for the management of recurrent HNC. Future groups developing recommendations for this purpose should implement the AGREE II framework to improve quality and standardization of their guidelines., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The association between ibuprofen use and severity of post-tonsillectomy hemorrhage (PTH) remains unclear. We aimed to compare PTH severity in patients who did or did not receive ibuprofen., Methods: A retrospective cohort study of pediatric patients requiring operative control of PTH at a tertiary children's hospital between 2015 and 2019 was performed. PTH severity was assessed using pre-tonsillectomy and post-hemorrhage hemoglobin and hematocrit values, estimated intraoperative blood loss, estimated hemorrhage flow rate, and need for transfusion. Differences in hemorrhage severity markers between the two cohorts were compared., Results: A total of 168 consecutive patients were included in this study. The mean age was 8.8 years, and 55.4% of patients were male. Sixty-five patients (38.7%) received ibuprofen postoperatively. There was no statistically significant difference in the mean change in hemoglobin (1.1 vs. 1.1, P = 0.85) or hematocrit (3.1 vs. 3.2, P = 0.97) between patients who received ibuprofen compared to those who did not. Similarly, there were no significant differences in need for transfusion (3.1% vs. 3.9%, P = 1.00) or occurrence of high-flow (arterial) blood loss (33.8% vs. 40.8%, P = 0.42) between the two groups., Conclusion: Postoperative ibuprofen use does not appear to significantly increase PTH severity, as measured by change in hemoglobin and hematocrit values, need for transfusion, or presence of high-flow blood loss. This study introduces previously unexplored markers to assess PTH severity and supports further prospective studies to determine the effect of ibuprofen on PTH severity., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Laryngeal injuries are rare but life-threatening airway emergencies. Increased understanding of the epidemiology of these injuries can inform treatment and improve outcomes. We aimed to characterize the demographics and management of adult laryngeal trauma., Methods: The National Trauma Data Bank (NTDB) was queried from 2007 to 2015 for patients ≥18 years old with laryngeal trauma. Patient demographics, injury characteristics, and treatment course were collected. Outcomes were assessed via multivariate logistic regression., Results: From 7.3 million patients, 6,890 (0.1%) patients with laryngeal trauma were identified. Eighty-five percent of patients were male, and the median age was 40. Of these patients, 343 (5.0%) were dead on arrival and of the remaining patients, 510 (7.8%) of patients were deceased at discharge. Common concomitant injuries included facial fractures (27%), intracranial injuries (21%), and rib and sternum fractures (19%). The most common cause of injury was motor vehicle accident (26%), followed by assault with firearms/explosives (12%) and assault with cutting instruments (8%). Forty-three percent of patients received mechanical ventilation and 15% received surgical repair. After correcting for gender, age, and injury severity, firearm injuries (odds ratio [OR] 3.46, 95% CI: [2.88-4.15]) and cutting/piercing injuries (OR 2.23, 95% CI: [1.89-2.64]) were positively associated with the need for mechanical ventilation. Motor vehicle trauma (OR 0.63, 95% CI: [0.46-0.84]) was negatively associated with surgical repair while striking injuries (OR 1.61, 95% CI: [1.25-2.06]) were positively associated. Lastly, shorter time to tracheostomy was significantly associated with shorter ICU stays (p &lt; 0.0001)., Conclusion: This study is the largest epidemiologic study of laryngeal trauma to date and identifies the risk of surgical intervention with firearm and cutting injuries as well as the importance of earlier time to tracheostomy for ICU management., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: To evaluate the current quality and utility of clinical practice guidelines (CPGs) issued for the diagnosis, prevention, and treatment of medication-related osteonecrosis of the jaw (MRONJ)., Study Design: We performed a systematic literature search of guidelines for MRONJ diagnosis, staging, prevention, or management. An appraisal of guidelines was completed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Scaled domain scores were calculated for each domain. Key recommendations were abstracted from guidelines distinguished as "high" quality., Results: Six CPGs were identified from systematic review. Four of 6 (66.7%) guidelines were published within the last 2 years. Each guideline discussed management of antiresorptive and antiangiogenic therapy-associated osteonecrosis of the jaw. The highest-scoring domain was domain 1: "Scope and purpose," with an average score of 85.0% (range: 76.4%-100.0%). The lowest domain score was in domain 5: "Applicability," with an average score of 41.7% (range: 22.9%-92.7%). Only 2 guidelines (33.3%) met the quality threshold of > 60% in 5 or more AGREE II domains, distinguishing them as "high"-quality guidelines. The average kappa statistic calculated across domains was 0.77, suggesting substantial interrater correlation in the CPG appraisal process., Conclusions: Despite the increasing recognition of MRONJ as a debilitating consequence of antiresorptive and antiangiogenic therapy, clinical guideline recommendations may be lacking in overall quality and clinical utility., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sentinel lymph node biopsy (SLNB) is a minimally invasive surgical procedure that is standard of care for the evaluation of clinically negative regional lymph nodes in patients with cutaneous melanoma. As the presence of metastases dictates patient prognosis and determines the need for further regional disease control or adjuvant therapy, SLNB is invaluable to clinical decision-making in patients presenting with melanoma. However, the indications for SLNB, specifically among patients with thin (<1 mm) or thick (>4 mm) melanomas, remain unclear. A number of clinical practice guidelines (CPGs) have been developed outlining recommendations for the role of lymph node biopsy in the management of melanoma. However, to date, their quality has not been critically appraised. Our objective was to systematically evaluate all available CPGs on this topic using the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Four total guidelines met the inclusion criteria and underwent appraisal. Only one CPG achieved a "high" quality rating, indicating scores of >60% in at least five of the six AGREE II domains. Across all CPGs, the lowest scoring domains were "Applicability" and "Stakeholder involvement," which had average scores of 41.2% and 48.3%, respectively. Based on the AGREE II instrument, the quality of existing CPGs for the indications of SLNB for melanoma is low. Future guidelines should be pilot tested to evaluate barriers to application and should utilize multidisciplinary guideline development teams that include patients and key stakeholders in addition to clinical experts from all relevant disciplines., (© 2022. Society of Surgical Oncology.)

Purpose: Medullary thyroid carcinoma (MTC) is a rare and aggressive form of thyroid neoplasia that requires multidisciplinary collaboration for effective management. We systematically appraise the quality of clinical practice guidelines (CPG) for the diagnosis and treatment of MTC using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument., Materials and Methods: A systematic literature search was performed to identify CPGs pertaining to the diagnosis and treatment of MTC. Data were abstracted from guidelines meeting inclusion criteria and appraised by four independent reviewers in the six domains of quality defined by the AGREE II. Intraclass correlation coefficients (ICC) were calculated across domains to qualify interrater reliability., Results: Fourteen guidelines met inclusion criteria. No guideline achieved a score of >60 % in five or more AGREE II quality domains, which is required to gain designation as 'high' quality. One "average quality" guideline authored by the British Thyroid Association achieved a score of >60 % in three quality domains. The remaining thirteen (92.9 %) CPGs demonstrated low quality content, with deficits most pronounced in domains 3, 5, and 6, suggesting a lack of rigorously developed, clinically applicable, and transparent information., Conclusions: As the diagnosis and treatment of MTC continues to evolve, the development of high-quality guidelines becomes increasingly important; few existing meet appropriate standards., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Infantile hemangiomas (IH) are the most common benign tumors of childhood. Timely diagnosis and management of higher-risk IH is key in avoiding permanent disfigurement, visual impairment, and life-threatening airway compromise. Here, we identify and critically appraise existing clinical practice guidelines (CPGs) for IH diagnosis and management. A systematic search of MEDLINE, SCOPUS, and EMBASE was conducted until August 2021. Four independent reviewers assessed each CPG utilizing the Appraisal of Guidelines for Research and Evaluation, 2 nd edition (AGREE II). An scaled domain score of ≥60% demonstrated adequacy in a given domain. Intraclass correlation coefficients (ICC) assessed agreement and scoring consistency between the reviewers. Eight CPGs were eligible and included for critical appraisal. Only one CPG was classified as 'high quality', with the remaining seven guidelines being 'average' ( n  = 3) or 'low' ( n  = 4) quality. Six guidelines (75.0%) were conducted via nonsystematic literature searches. The 'Applicability' (40.4%±14.0) and 'Rigor of development' (46.9%±17.3) domains achieved the lowest scores, while the highest average scores were in 'Scope and purpose' (76.7%±11.3) and 'Editorial independence' (90.8%±13.0). We found high consistency between the four independent reviewers, with 'very good' ( n  = 5) or 'good' ( n  = 1) interrater reliability in all six AGREE II domains. Based on the AGREE II instrument, there is only one available high-quality consensus statement on the diagnosis and management of IH. Low scores in 'Rigor of development' and 'Applicability' suggest notable weaknesses in the development process and reporting quality of existing IH CPGs. Future guidelines should be backed by systematic literature searches and focus on guideline clinical translation.

Objectives: Otolaryngology-specific requirements were piloted to minimize applicant and program burdens. We investigated the impact of introducing and then removing these requirements on Match outcomes., Methods: 2014-2021 National Resident Matching Program® data were examined. The primary outcome was the impact of Otolaryngology Resident Talent Assessment (ORTA; prematch 2017, postmatch 2019) and Program-Specific Paragraph (PSP; implemented 2016, optional 2018) on applicant numbers and match rates. Secondary survey analysis assessed candidate perceptions of PSP/ORTA., Results: Applicant numbers declined significantly during PSP/ORTA (18.9%; p  = 0.001). With the optional PSP and postmatch ORTA, applicant numbers increased significantly (39.0%;  p  = 0.002). Examined individually, mandatory PSP was associated with a significant decline in applicants ( p  = 0.007), whereas postmatch ORTA was associated with significant increases in applicants ( p  = 0.010). ORTA and PSP negatively impacted the decision to apply to otolaryngology in 59.8% and 51.3% of applicants, respectively. Conversely, match rate success improved significantly from 74.8% to 91.2% during PSP/ORTA ( p  = 0.014), followed by a significant decline to 73.1% after PSP was made optional and ORTA moved to postmatch ( p  = 0.002)., Conclusions: ORTA and PSP correlated with decreased applicant numbers and increased match rate success. As programs seek ways to remove barriers to applying to otolaryngology, the potential consequences of an increasing pool of unmatched candidates must also be considered., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons, Ltd on behalf of Chinese Medical Association.)

Objective: Although standard of care for primary nasopharyngeal carcinoma (NPC) is chemoradiotherapy, there remains no consensus on management of recurrent or metastatic disease. We characterized recent clinical trials on NPC to assess trends in NPC treatment and establish promising areas for future research., Study Design: Retrospective database study., Setting: ClinicalTrials.gov database., Methods: Retrospective review of all NPC trials from November 1999 to June 2021. For each study, the following variables were extracted: study characteristics, intervention, outcome measures, and inclusion criteria. Secondary searches via PubMed and Google scholar determined trial publication status., Results: A total of 448 clinical trials were identified: 72 (16%) observational and 376 (84%) interventional, of which there were 30 (8%) Phase I, 183 (49%) Phase II, 86 Phase III (23%), and 5 (1%) Phase IV trials. Fifty-four percent of trials included only primary NPC while 111 (25%) exclusively studied recurrent cancers. The most common interventions were cisplatin ( n  = 64) and intensity modulated radiation therapy ( n  = 54); there were 38 trials involving PD-1 monoclonal antibodies. Thirty-four studies examined quality of life measures, including xerostomia and mucositis. Of the completed studies, 53.2% have published manuscripts. Poor patient accrual was the most common reason for premature study termination., Conclusions: Novel immunotherapies have been increasingly incorporated into NPC studies in recent years, however, chemotherapy and radiation, despite their numerous side effects, are still widely used due to their clinical effectiveness. Future trials are warranted to determine the optimal therapeutic regimens to decrease relapse rates and side effects., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

Objective: To assess the feasibility and effectiveness of indocyanine green (ICG) for image-guided resection of head and neck cancer (HNC)., Data Sources: PubMed, Embase, and Scopus databases., Review Methods: Searches were conducted from database inception to February 2022. Patient and study characteristics, imaging parameters, and imaging efficacy data were extracted from each study., Results: Nine studies met inclusion criteria, representing 103 head and neck tumors. Weighted mean ICG dose and imaging time were 1.27 mg/kg and 11.77 h, respectively. Among the five studies that provided quantitative metrics of imaging efficacy, average ICG tumor-to-background ratio (TBR) was 1.56 and weighted mean ONM-100 TBR was 3.64. Pooled sensitivity and specificity across the five studies were 91.7 % and 71.9 %, respectively., Conclusion: FGS with ICG may facilitate real-time tumor-margin delineation to improve margin clearance rates and progression-free survival. Future studies with validated, quantitative metrics of imaging success are necessary to further evaluate the prognostic benefit of these techniques., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Compared to microscopes, exoscopes have advantages in field-depth, ergonomics, and educational value. Exoscopes are especially well-poised for adaptation into fluorescence-guided surgery (FGS) due to their excitation source, light path, and image processing capabilities. We evaluated the feasibility of near-infrared FGS using a 3-dimensional (3D), 4 K exoscope with nearinfrared fluorescence imaging capability. We then compared it to the most sensitive, commercially-available near-infrared exoscope system (3D and 960 p). In-vitro and intraoperative comparisons were performed., Methods: Serial dilutions of indocyanine-green (1-2000 μg/mL) were imaged with the 3D, 4 K Olympus Orbeye (system 1) and the 3D, 960 p VisionSense Iridium (system 2). Near-infrared sensitivity was calculated using signal-to-background ratios (SBRs). In addition, three patients with brain tumors were administered indocyanine-green and imaged with system 1, with two also imaged with system 2 for comparison., Results: Systems 1 and 2 detected near-infrared fluorescence from indocyanine green concentrations of >250 μg/L and >31.3 μg/L, respectively. Intraoperatively, system 1 visualized strong near-infrared fluorescence from two, strongly gadoliniumenhancing meningiomas (SBR=2.4, 1.7). The high-resolution, bright images were sufficient for the surgeon to appreciate the underlying anatomy in the near-infrared mode. However, system 1 was not able to visualize fluorescence from a weakly-enhancing intraparenchymal metastasis. In contrast, system 2 successfully visualized both the meningioma and the metastasis but lacked high resolution stereopsis., Conclusion: Three-dimensional exoscope systems provide an alternative visualization platform for both standard microsurgery and near-infrared fluorescent guided surgery. However, when tumor fluorescence is weak (i.e., low fluorophore uptake, deep tumors), highly sensitive near-infrared visualization systems may be required.

Introduction: Radiofrequency ablation (RFA) has gained significant recent global interest in the treatment of benign thyroid nodules and thyroid cancer. It is a relatively new, minimally invasive, thermal ablation technique that is an alternative to surgery. Several clinical practice guidelines (CPGs), consensus statements, and recommendations currently exist for the use of RFA in the treatment of benign thyroid nodules and thyroid cancers. These documents have considerable variability amongst them, and to date, their quality and methodologic rigor have not been appraised., Objective: To identify and perform a quality appraisal of clinical practice guidelines for RFA in the treatment of benign thyroid nodules and thyroid cancer using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool., Methods: A comprehensive literature search was performed in MEDLINE (via PubMed), EMBASE, and SCOPUS databases from inception to November 1, 2021. Four reviewers independently evaluated each guideline using the AGREE II instrument. Scaled domain scores were generated and the threshold used for satisfactory quality was >60%. Additionally, intraclass correlation coefficients (ICCs) were calculated to determine level of agreement between reviewers., Results: Seven guidelines were selected for final evaluation based on inclusion/exclusion criteria. Two guidelines were classified "high" quality, one "average" quality, and the rest "low" quality. The "Clarity and Presentation" (65.68 ± 26.1) and "Editorial Independence" (61.32 ± 25.8) domains received the highest mean scores, while the "Applicability" (32.14 ± 22.8) and "Rigor of Development" (45.02 ± 29.8) domains received the lowest mean scores. ICC statistical analysis showed high magnitude of agreement between reviewers with a range of (0.722-0.944)., Conclusion: Reflecting upon our quality appraisal, it is evident that the quality and methodologic rigor of RFA guidelines can be improved upon in the future. Our findings also elucidate the existing variability/discrepancies amongst guidelines in the indications and use of RFA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We demonstrate a safe and effective surgical technique for the operative management of Eagle syndrome, also known as stylohyoid syndrome, via transcervical styloidectomy. Fifteen patients who presented to our institution for surgical management of Eagle syndrome were included. A detailed video shows the operative techniques used to perform styloidectomy via a transcervical approach. The procedure was well tolerated without complications, and all patients were discharged on postoperative day one. Thirteen patients (87%) endorsed significant improvement or complete resolution of their presenting complaint(s), most commonly throat and neck pain/discomfort (53%), otalgia (47%), and/or tinnitus (40%). The transcervical approach for styloidectomy provides an alternative for operative access that overcomes the limitations associated with the transoral approach. It enables better exposure of the operative field, a more efficient procedure, and, in the senior author's experience, results in decreased postoperative pain, trismus, and length of hospital stay., (© 2022 Wiley Periodicals LLC.)

We performed a systematic review to characterize reconstructive modalities and postoperative surgical outcomes following TORS resection. A search of the PubMed, SCOPUS, and EMBASE databases was conducted to identify studies describing patients undergoing reconstruction of TORS defects. Twenty-six studies met inclusion criteria, consisting of 260 patients who underwent TORS resection followed by reconstruction. Twenty-one studies reported tumor classification information, with TORS performed for 44 (23.0%) T1, 86 (45.0%) T2, 33 (17.3%) T3, and 28 (14.7%) T4 tumors. Eighteen distinct reconstructive modalities were described in the studies identified, including nine unique free flap types. The most commonly performed reconstruction was the radial forearm free flap (RFFF), accounting for 121/260 (46.5%) of reconstructions performed. Reported surgical complications included 5 pharyngocutaneous fistulae, 13 hemorrhagic complications, 24 infectious complications, and 5 free flap failures. Our findings demonstrate favorable surgical outcomes but minimal quantitative functional data to compare reconstructive options following TORS., (© 2022 Wiley Periodicals LLC.)

Purpose: We identified and appraised clinical practice guidelines (CPGs) for the management of post-tonsillectomy pain using the Appraisal of Guidelines for Research and Evaluation (AGREE II) guideline research tool., Materials and Methods: We conducted a literature search to identify CPGs addressing pain management after tonsillectomy. CPGs meeting inclusion criteria were then appraised by four independent reviewers in six areas of quality, as defined by AGREE II. Scaled domain scores were calculated for each quality domain. Intraclass correlation coefficients (ICC) were calculated in each domain to assess interrater reliability across guideline appraisals., Results: Nine guidelines meeting inclusion criteria were identified from a systematic search of the literature. The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guideline detailing tonsillectomy and postoperative management in pediatric patients received the highest average score, with a mean of 90.1% in the six areas of quality. Three guidelines scored higher than >60% in five domains or more, defining 'high' quality per AGREE II: AAO-HNS, Scottish Intercollegiate Guides Network (SIGN), and Ontario Ministry of Health CPGs. The highest-scoring domain was domain 4: Clarity of presentation (87.4%) across guidelines, while the lowest scoring domain was domain 5: Applicability (49.4%). Variability in scaled domain scores between all CPGs was relatively consistent across domains, with a mean standard deviation of 22.4%. The average ICC calculated across all six domains was 0.78, indicating 'strong agreement' between reviewers regarding guideline quality., Conclusion: Of the nine available guidelines detailing pain management following tonsillectomy we identified, only three (33%) were deemed 'high'-quality after appraisal using the AGREE II instrument, suggesting a need for development of novel, methodologically rigorous CPGs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The use of 5-aminolevulinic acid (5-ALA) for intraoperative protoporphyrin IX fluorescent imaging in the resection of malignant gliomas has been demonstrated to improve tumor visualization, increase the extent of resection, and extend progression-free survival. The current technique for visualization of 5-ALA consists of excitation and emission filters built into the operating microscope. However, there are notable limitations to this process, including low quantum yield, expense, and masking of surrounding anatomy., Methods: We present 3 cases in which 3 separate methods were employed for visualizing fluorescence. The devices reported are 1) a low-cost blue light flashlight, 2) a low-cost headlamp, and 3) the first reported case of the new Designs for Vision REVEAL Fluorescence-Guided Surgery (FGS) 5-ALA fluorescent headlight and loupes. The aim of the study is to provide confirmation that tumor fluorescence can be observed using commercially available products other than the microscope., Results: We demonstrate through 3 intraoperative cases that a variety of devices can produce visible fluorescence of the high-grade tumor and allow for simultaneous real-time visualization of the adjacent brain parenchyma and vasculature. The REVEAL FGS system appears to offer increased fluorescence emission compared with all other methods, including the microscope., Conclusions: Our study demonstrates the feasibility of using blue/ultraviolet light supplied by a commercially available, inexpensive flashlight or headlamp to visualize 5-ALA fluorescence in high-grade gliomas. We also provide the first documentation of the intraoperative use of the new Designs for Vision REVEAL FGS 5-ALA fluorescent headlight and loupes and report on the experience. Lack of an operative microscope capable of fluorescent illumination should not be a limiting factor in performing fluorescent-guided glioma resection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Fluorescence-guided surgery may improve completeness of resection in transsphenoidal surgery for Cushing disease (CD) by enabling visualization of residual tumor tissue at the margins. In this review we discuss somatostatin receptors (SSTRs) as targets for fluorescence-guided surgery and overview existing SSTR-specific imaging agents. We also compare SSTR expression in normal pituitary and corticotrophinoma tissues from human and canine CD patients to assess canines as a translational model for CD., Methods: A PubMed literature search was conducted for publications containing the terms canine, somatostatin receptor, Cushing's disease, and corticotroph adenoma. SSTR expression data from each study was documented as the presence or absence of expression or, when possible, the number of tumors expressing a given SSTR subtype within a group of tumors being studied. Studies that used reverse transcription polymerase chain reaction to quantify SSTR expression were selected for additional comparative analysis., Results: SSTR5 is strongly expressed in human corticotroph adenomas and weakly expressed in surrounding pituitary parenchyma, a pattern not conclusively observed in canine patients. SSTR2 mRNA expression is similar in human normal pituitary and corticotrophinoma cells but may be significantly higher in canine normal pituitary tissue than in corticotroph tumoral tissue. Limited data were available on SSTR subtypes 1, 3, and 4., Conclusions: Further studies must fill the knowledge gaps related to species-specific SSTR expression, so using canine CD as a translational model may be premature. We do conclude that the expression profile of SSTR5 (i.e., high local expression in pituitary adenomas relative to normal surrounding tissues) makes SSTR5 a promising molecular target for FGS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Metastases are the most common intracranial malignancies and complete resection can provide relief of neurological symptoms and reduce recurrence. The authors' prospective pilot study in 2017 demonstrated promising results for the application of high-dose, delayed imaging of indocyanine green (ICG), known as second window ICG (SWIG), in patients undergoing surgery for brain metastases. In this prospective cohort study, the authors evaluated intraoperative imaging and clinical outcomes of treatment using SWIG., Methods: Patients were prospectively enrolled in an approved study of high-dose, delayed ICG (SWIG) and received 5 mg/kg (2014-2018) or 2.5 mg/kg (2018-2019) ICG 24 hours preoperatively. Intraoperatively, near-infrared (NIR) imaging was performed using a dedicated NIR exoscope. NIR images were analyzed and the signal-to-background ratio (SBR) was calculated to quantify fluorescence. Residual fluorescence on the postresection NIR view was compared and correlated to the residual gadolinium enhancement on postoperative MRI. Patient survival and predictive factors were analyzed., Results: In total, 51 intracranial metastases were surgically treated in 47 patients in this cohort. All 51 metastatic tumors demonstrated strong NIR fluorescence (mean SBR 4.9). In tumors ≤ 10 mm from the cortical surface, SWIG with 5 mg/kg ICG produced enhanced transdural tumor visibility (91.3%) compared to 2.5 mg/kg (52.9%; p = 0.0047). Neoplastic margin detection using NIR fluorescence compared to white light improved sensitivity, albeit lowered specificity; however, increasing the SBR cutoff for positive fluorescence significantly improved specificity without sacrificing sensitivity, increasing the overall accuracy from 57.5% to 72.5%. A lack of residual NIR fluorescence after resection was closely correlated with a lack of residual enhancement on postoperative MRI (p = 0.007). Among the 16 patients in whom tumor recurred at the site of surgery, postoperative MRI successfully predicted 8 cases, whereas the postresection NIR view predicted 12 cases. Progression-free survival rate at 12 months was greater for patients without residual NIR fluorescence (38%) than for those without residual enhancement on postoperative MRI (29%)., Conclusions: The current study demonstrates the clinical benefits of the SWIG technique in surgery for patients with brain metastases. Specifically, this technique allows for dose-dependent, transdural localization of neoplasms and improved sensitivity in neoplastic margin detection. Postresection residual fluorescence can be a powerful tool to evaluate extent of resection in conjunction with MRI, and it may guide decisions on brain metastasis management.

Background and Importance: The proper differentiation of neoplastic tissue from adjacent brain parenchyma can pose a great challenge, especially in eloquent areas of the brain. With the novel technique, "Second-Window Indocyanine Green," injection of a near-infrared fluorophore (ICG) allows for intraoperative visualization of tumors by taking advantage of the compromised vasculature surrounding the tumor. Thus, such a technique may demonstrate utility for hemangioblastomas, which are hypervascular tumors of the central nervous system., Clinical Presentation: Here we present the case of a 39-yr-old male with a demonstrated cystic mass in the left cerebellum, with additional edema spreading towards the vermis. A total of 5 mg/kg of ICG was delivered intravenously 24 h prior to the operation. The tumor was approached via the infratentorial suboccipital approach. We observed strong near-infrared fluorescence through the intact dura, consistent with the tumor location. Surgical pathology confirmed a final diagnosis of cerebellar hemangioblastoma. There was complete resection of the tumor, with the patient discharged uneventfully., Conclusion: We report the first successful case of fluorescence-guided surgery of a cerebellar hemangioblastoma using near-infrared fluorescence imaging with the Second-Window ICG technique. This joins a growing series of publications that demonstrate the efficacy of a novel application of ICG, a near-infrared fluorophore, in accurate intraoperative visualization of neoplastic tissue. While the use of a dedicated near-infrared platform (ie, the VisionSense Iridium [Visionsense, Philadelphia, Pennsylvania]) yields a higher signal-to-background ratio, a neurosurgical microscope (ie, the Leica OH6 [Leica Microsystems, Wetzlar, Germany]) may also provide a suitable option in cases where fluorescence is very strong., (© Congress of Neurological Surgeons 2021.)

Purpose: Fluorescence-guided-surgery offers intraoperative visualization of neoplastic tissue. Delta-aminolevulinic acid (5-ALA), which targets enzymatic abnormality in neoplastic cells, is the only approved agent for fluorescence-guided neurosurgery. More recently, we described Second Window Indocyanine Green (SWIG) which targets neoplastic tissue through enhanced vascular permeability. We hypothesized that SWIG would demonstrate similar clinical utility in identification of high-grade gliomas compared with 5-ALA., Procedures: Female C57/BL6 and nude/athymic mice underwent intracranial implantation of 300,000 GL261 and U87 cells, respectively. Tumor-bearing mice were euthanized after administration of 5-ALA (200 mg/kg intraperitoneal) and SWIG (5 mg/kg intravenous). Brain sections were imaged for protoporphyrin-IX and ICG fluorescence. Fluorescence and H&E images were registered using semi-automatic scripts for analysis. Human subjects with HGG were administered SWIG (2.5 mg/kg intravenous) and 5-ALA (20 mg/kg oral). Intraoperatively, tumors were imaged for ICG and protoporphyrin-IX fluorescence., Results: In non-necrotic tumors, 5-ALA and SWIG demonstrated 90.2 % and 89.2 % tumor accuracy (p value = 0.52) in U87 tumors and 88.1 % and 87.7 % accuracy (p value = 0.83) in GL261 tumors. The most distinct difference between 5-ALA and SWIG distribution was seen in areas of tumor-associated necrosis, which often showed weak/no protoporphyrin-IX fluorescence, but strong SWIG fluorescence. In twenty biopsy specimens from four subjects with HGG, SWIG demonstrated 100 % accuracy, while 5-ALA demonstrated 75-85 % accuracy; there was 90 % concordance between SWIG and 5-ALA fluorescence., Conclusion: Our results provide the first direct comparison of the diagnostic utility of SWIG vs 5-ALA in both rodent and human HGG. Given the broader clinical utility of SWIG compared with 5-ALA, our data supports the use of SWIG in tumor surgery to improve the extent of safe resections., Clinical Trial: NCT02710240 (US National Library of Medicine Registry; https://www.clinicaltrials.gov/ct2/show/NCT02710240?id=NCT02710240&draw=2&rank=1 ).

Purpose: Intraoperative molecular imaging with tumor-targeting fluorophores offers real-time detection of neoplastic tissue. The second window indocyanine green (SWIG) technique relies on passive accumulation of indocyanine green (ICG), a near-infrared fluorophore, in neoplastic tissues. In this study, we explore the ability of SWIG to detect neoplastic tissue and to predict postoperative magnetic resonance imaging (MRI) findings intraoperatively., Procedures: Retrospective data were collected from 36 patients with primary high-grade gliomas (HGG) enrolled as part of a larger trial between October 2014 and October 2018. Patients received systemic ICG infusions at 2.5-5 mg/kg 24 h preoperatively. Near-infrared fluorescence was recorded throughout the case and from biopsy specimens. The presence/location of residual SWIG signal after resection was compared to the presence/location of residual gadolinium enhancement on postoperative MRI. The extent of resection was not changed based on near-infrared imaging., Results: All 36 lesions demonstrated strong near-infrared fluorescence (signal-to-background = 6.8 ± 2.2) and 100 % of tumors reaching the cortex were visualized before durotomy. In 78 biopsy specimens, near-infrared imaging demonstrated higher sensitivity and accuracy than white light for diagnosing neoplastic tissue intraoperatively. Furthermore, near-infrared imaging predicted gadolinium enhancement on postoperative MRI with 91 % accuracy, with visualization of residual enhancement as small as 0.3 cm 3 . Patients with no residual near-infrared signal after resection were significantly more likely to have complete resection on postoperative MRI (p value < 0.0001)., Conclusions: Intraoperative imaging with SWIG demonstrates highly sensitive detection of HGG tissue in real time. Furthermore, post-resection near-infrared imaging correlates with postoperative MRI. Overall, our findings suggest that SWIG can provide surgeons with MRI-like results in real time, potentially increasing resection rates.

Introduction: Glioblastoma multiforme (GBM) is the most common primary intracranial malignancy; survival can be improved by maximizing the extent-of-resection., Methods: A near-infrared fluorophore (Indocyanine-Green, ICG) was combined with a photosensitizer (Chlorin-e6, Ce6) on the surface of superparamagnetic-iron-oxide-nanoparticles (SPIONs), all FDA-approved for clinical use, yielding a nanocluster (ICS) using a microemulsion. The physical-chemical properties of the ICS were systematically evaluated. Efficacy of photodynamic therapy (PDT) was evaluated in vitro with GL261 cells and in vivo in a subtotal resection trial using a syngeneic flank tumor model. NIR imaging properties of ICS were evaluated in both a flank and an intracranial GBM model., Results: ICS demonstrated high ICG and Ce6 encapsulation efficiency, high payload capacity, and chemical stability in physiologic conditions. In vitro cell studies demonstrated significant PDT-induced cytotoxicity using ICS. Preclinical animal studies demonstrated that the nanoclusters can be detected through NIR imaging in both flank and intracranial GBM tumors (ex: 745 nm, em: 800 nm; mean signal-to-background 8.5 ± 0.6). In the flank residual tumor PDT trial, subjects treated with PDT demonstrated significantly enhanced local control of recurrent neoplasm starting on postoperative day 8 (23.1 mm 3 vs 150.5 mm 3 , p = 0.045), and the treatment effect amplified to final mean volumes of 220.4 mm 3 vs 806.1 mm 3 on day 23 (p = 0.0055)., Conclusion: A multimodal theragnostic agent comprised solely of FDA-approved components was developed to couple optical imaging and PDT. The findings demonstrated evidence for the potential theragnostic benefit of ICS in surgical oncology that is conducive to clinical integration.

Despite the substantial growth of telemedicine and the evidence of its advantages, the use of telemedicine in neurosurgery has been limited. Barriers have included medicolegal issues surrounding provider reimbursement, interstate licensure, and malpractice liability as well as technological challenges. Recently, the coronavirus disease 2019 (COVID-19) pandemic has limited typical evaluation of patients with neurologic issues and resulted in a surge in demand for virtual medical visits. Meanwhile, federal and state governments took action to facilitate the rapid implementation of telehealth programs, placing a temporary lift on medicolegal barriers that had previously limited its expansion. This created a unique opportunity for widespread telehealth use to meet the surge in demand for remote medical care. After initial hurdles and challenges, our experience with telemedicine in neurosurgery at Penn Medicine has been overall positive from both the provider and the patients' perspective. One of the unique challenges we face is guiding patients to appropriately set up devices in a way that enables an effective neuroexamination. However, we argue that an accurate and comprehensive neurologic examination can be conducted through a telemedicine platform, despite minor weaknesses inherent to absence of physical presence. In addition, certain neurosurgical visits such as postoperative checks, vascular pathology, and brain tumors inherently lend themselves to easier evaluation through telehealth visits. In the era of COVID-19 and beyond, telemedicine remains a promising and effective approach to continue neurologic patient care., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Checkpoint inhibition has established immunotherapy as a major modality of cancer treatment. However, the success of cancer immunotherapy is still limited as immune regulation of tumor immunity is very complicated and mechanisms involved may also differ among cancer types. Beside checkpoints, other good candidates for immunotherapy are immunosuppressive cytokines. TGF-β is a very potent immunosuppressive cytokine involved in suppression of tumor immunity and also necessary for the function of some regulatory cells. TGF-β has three isoforms, TGF-β 1, 2 and 3. It has been demonstrated in multiple mouse tumor models that inhibition of all three isoforms of TGF-β facilitates natural tumor immunosurveillance and tumor vaccine efficacy. However, individual isoforms of TGF-β are not well studied yet. Here, by using monoclonal antibodies (mAbs) specific for TGF-β isoforms, we asked whether it is necessary to inhibit TGF-β3 to enhance tumor immunity. We found that blockade of TGF-β1 and 2 and of all isoforms provided similar effects on tumor natural immunosurveillance and therapeutic vaccine-induced tumor immunity. The protection was CD8 + T cell-dependent. Blockade of TGF-β increased vaccine-induced Th1-type response measured by IFNγ production or T-bet expression in both tumor draining lymph nodes and tumors, although it did not increase tumor antigen-specific CD8 + T cell numbers. Therefore, protection correlated with qualitative rather than quantitative changes in T cells. Furthermore, when combined with PD-1 blockade, blockade of TGF-β1 and 2 further increased vaccine efficacy. In conclusion, blocking TGF-β1 and 2 is sufficient to enhance tumor immunity, and it can be further enhanced with PD-1 blockade.