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Objective(s): Coins are the most frequently ingested foreign bodies by children. While rigid esophagoscopy with concomitant intubation is frequently used for removal, it has the potential for serious complications. We aimed to assess and compare the safety, efficacy, and efficiency of two different techniques for pediatric cervical esophageal coin removal., Methods: Retrospective chart review identified patients who underwent esophageal coin removal from January 2017-August 2023 at one of two tertiary academic centers: Ann & Robert H. Lurie Children's Hospital and Yale-New Haven Hospital. Patients with foreign bodies other than coins were excluded. Patients underwent one of two approaches for cervical esophageal coin removal depending on surgeon preference: (1) induction of general anesthesia, intubation, rigid esophagoscopy, and coin extraction with optical forceps (esophagoscope group) or (2) mask ventilation, insertion of a straight laryngoscope blade into the esophagus orifice, and coin extraction with alligator forceps (straight laryngoscope group). Primary outcomes were successful removal of the esophageal coin, regarded a marker of efficacy, as well as operative and anesthesia times, which were regarded as measures of efficiency. Secondary outcomes were postoperative complications, regarded as markers of safety., Results: Of the 108 patients meeting inclusion criteria, 23 (21.3%) were in the straight laryngoscope group and 85 (78.7%) in the esophagoscope group. Mean operative time was significantly shorter for the straight laryngoscope group compared to the esophagoscope group (2.8 ± 1.5 minutes vs 13.8 ± 17.2 minutes, respectively, p  < .0001). Mean anesthesia time was significantly shorter for the straight laryngoscope group compared to the esophagoscope group (24.2 ± 6.4 minutes vs 44.7 ±1 6.2 minutes, respectively, p  < .0001). There were no intra- or post-operative complications in the straight laryngoscope group and two minor complications in the esophagoscope group., Conclusions: Esophagoscopy using a straight laryngoscope blade under mask anesthesia can represent a safe and efficient alternative for impacted esophageal coin removal., 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.

Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in children. According to developmental literature findings, there is a link between executive function (EF) and ADHD. Although EF deficits vary across ADHD presentations in children, working memory capacity is commonly associated with attention impairments. Notably, deficits in working memory capacity are also observed in frequent mind wandering reports for typically developing children. Mind wandering is shifting attention away from a current task to an unrelated thought. To explore the relationship between EF and mind wandering in children with ADHD ( n = 47) and further compare our current sample to a typically developing (control) group from a previous study ( n = 47), all participants completed three EF-related tasks. They concurrently reported if they were on task or mind wandering. Our results indicate better short-term memory capacity predicted lower mind wandering frequency in children who reported high levels of ADHD symptoms. Similar trends were observed for working memory capacity and ADHD symptomatology. Children with ADHD also reported more overall and unintentional mind wandering on questionnaires compared to children without ADHD. However, the relationship between EF and mind wandering did not differ between these groups. The current study suggests memory-related cognitive abilities may inform our understanding and management of mind wandering in children, driving the development of interventions targeting attention regulation.

Importance: Recurrent human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is a relatively rare but serious disease with little empirical data. Previous works have studied patterns of recurrence in HPV-positive OPSCC, but only one has studied truly recurrent disease as opposed to persistent disease, and no work systematically analyzed posttreatment surveillance imaging strategies and how recurrences were detected., Objective: To refine the understanding of HPV-positive OPSCC recurrence and inform optimal imaging surveillance strategies., Design, Setting, and Participants: This retrospective cohort study involved electronic medical record review at a tertiary care hospital. Patients treated for OPSCC from 2012 to 2019 were extracted, and patients diagnosed with HPV-positive OPSCC were identified. Data were analyzed from December 2022 to May 2023., Main Outcome Measures: Percentage of patients with a true recurrence, location of recurrence, time of recurrence detection, and method of recurrence detection. Recurrence was demonstrated with a scan after an imaging-established disease-free state 3 to 6 months posttreatment., Results: Of the 367 patients with HPV-positive OPSCC (mean [SD] age, 60.6 [9.2] years; 310 [84.5%] male), 37 (10.1%) experienced true disease recurrence. Median (IQR) follow-up time of the cohort was 3.6 years (8.5-88 months), defined as time from diagnosis to death or last contact. Within the true recurrence cohort, 21 patients (56.8%) experienced local, regional, or local and regional recurrence (LRR); 15 (40.5%) experienced distant metastasis (DM); and 1 (2.7%) experienced both LRR and DM. The mean (SD) time for detecting LRR was 2.46 (1.94) years and was considerably longer compared to the 1.89 (0.87) years for detecting DM (difference, 0.57 [95% CI, -0.29 to 1.02] years). The majority of patients identified their recurrence through symptom changes (31 [81.1%]) rather than through surveillance imaging (3 [8.1%])., Conclusion and Relevance: In this cohort study, 10.1% of patients experienced true HPV-positive OPSCC disease recurrence, with most incidences of DM occurring in the lung and brain. Disease recurrence was identified primarily through symptomatic change, suggesting that further research may be needed to understand the optimal surveillance strategies after definitive treatment.

Objective: We examined process-related quality metrics for oral squamous cell carcinoma (OSCC) depending on treating facility type across a health system and region., Study Design: Retrospective in accordance with Strengthening the Reporting of Observational Studies in Epidemiology guidelines., Setting: Single health system and region., Methods: Patients with OSCC diagnosed between 2012 and 2018 were identified from tumor registries of 6 hospitals (1 academic and 5 community) within a single health system. Patients were categorized into 3 care groups: (1) solely at the academic center, (2) solely at community facilities, and (3) combined care at academic and community facilities. Primary outcome measures were process-related quality metrics: positive surgical margin rate, lymph node yield (LNY), adjuvant treatment initiation ≤6 weeks, National Comprehensive Cancer Network (NCCN)-guideline adherence., Results: A total of 499 patients were included: 307 (61.5%) patients in the academic-only group, 101 (20.2%) in the community-only group, and 91 (18.2%) in the combined group. Surgery at community hospitals was associated with increased odds of positive surgical margins (11.9% vs 2.5%, odds ratio [OR]: 47.73, 95% confidence interval [CI]: 11.2-275.86, P < .001) and lower odds of LNY ≥ 18 (52.8% vs 85.9%, OR: 0.15, 95% CI: 0.07-0.33, P < .001) relative to the academic center. Compared with the academic-only group, odds of adjuvant treatment initiation ≤6 weeks were lower for the combined group (OR: 0.30, 95% CI: 0.13-0.64, P = .002) and odds of NCCN guideline-adherent treatment were lower in the community only group (OR: 0.35, 95% CI: 0.18-0.70, P = .003)., Conclusion: Quality of oral cancer care across the health system and region is comparable to or better-than national standards, indicating good baseline quality of care. Differences by facility type and fragmentation of care present an opportunity for bringing best in-class cancer care across an entire region., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

The E.3.3 mutation was generated in a Flp/FRT EMS screen for conditional mutations that cause growth and developmental defects in a genetic background that blocks apoptosis. The mutations were conditional, based on the Dark 82 allele being present on the starting chromosome, and blocking canonical apoptosis in a homozygous state. The E.3.3 mosaic eyes exhibit defects in eye development including patches of rough eye and irregular surface structure. Whole Genome Sequencing and complementation mapping revealed E.3.3 as an allele of prod . Prod is a DNA-binding protein that binds satellite repeats and is involved in chromocenter formation during mitosis. Here we present a novel allele of prod , prod E.3.3 , that disrupts the functional region of the Prod protein resulting in disruption of typical eye structure, likely due to disruption of chromatid separation during development., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Objective: Deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) has been shown to significantly improve motor symptoms for the treatment of medication-refractory Parkinson's disease. Yet, heterogeneity in clinical outcomes persists, possibly due to suboptimal target identification within the GPi. By leveraging robust sampling of the GPi and 6-month postsurgical outcomes, this study aims to determine optimal symptom-specific GPi DBS targets., Methods: In this study, the authors analyzed the anatomical lead location and 6-month postsurgical, double-blinded outcome measures of 86 patients who underwent bilateral GPi DBS. These patients were selected from the multicenter Veterans Affairs (VA)/National Institutes of Neurological Disorders and Stroke (NINDS) Cooperative Studies Program (CSP) 468 study to identify the optimal target zones ("sweet spots") for the control of overall motor (United Parkinson's Disease Rating Scale [UPDRS]-III), axial, tremor, rigidity, and bradykinesia symptoms. Lead coordinates were normalized to Montreal Neurological Institute space and the optimal target zones were identified and validated using a leave-one-patient-out approach., Results: The authors' findings revealed statistically significant optimal target zones for UPDRS-III (R = 0.37, p < 0.001), axial (R = 0.22, p = 0.042), rigidity (R = 0.20, p = 0.021), and bradykinesia (R = 0.23, p = 0.004) symptoms. These zones were localized within the primary motor and premotor subdivisions of the GPi. Interestingly, these zones extended beyond the GPi lateral border into the GPi-globus pallidus externa (GPe) lamina and into the GPe, but they did not reach the GPi ventral border, challenging traditional surgical approaches based on pallidotomies., Conclusions: Drawing upon a robust dataset, this research effectively delineates specific optimal target zones for not only overall motor improvement but also symptom subscores. These insights hold the potential to enhance the precision of targeting in subsequent bilateral GPi DBS surgical procedures.

Objective: While tobacco use is understood to negatively impact HPV+ oropharyngeal squamous cell carcinoma (OPSCC) outcomes, debate remains as to how this impact differs between cohorts. Multiple smoking metrics have been identified as having the greatest prognostic significance, and some recent works have found smoking to have no significant impact. Herein, we show through an analysis of four common smoking metrics that while smoking impacts overall survival (OS), it has a limited impact on recurrence-free survival (RFS) in our cohort., Methods: We conducted a retrospective review of patients treated for HPV+ OPSCC in our health system from 2012 to 2019. Patients with metastatic disease or concurrent second primaries were excluded. Four metrics of tobacco use were assessed: current/former/never smokers, ever/never smokers, and smokers with >10 or >20 pack-year (PY) smoking histories. Our main outcomes were 3-year RFS and OS., Results: Three hundred and sixty-seven patients met inclusion criteria. 37.3% of patients (137/367) were never-smokers; 13.8% of patients (51/367) were currently smoking at diagnosis and 48.8% of patients (179/367) were former smokers. No tobacco-use metric significantly impacted 3-year RFS. On univariate analysis, all smoking metrics yielded inferior OS. On multivariate analysis, current and ever smoking status significantly impacted 3-year OS., Conclusion: The impact of tobacco use on HPV+ OPSCC outcomes is not universal, but may instead be modulated by other cohort-specific factors. The impact of smoking may decrease as rates of tobacco use decline., Level of Evidence: 3 (Cohort and case-control studies) Laryngoscope, 134:3158-3164, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Understanding rhinoplasty characteristics important to patients, physicians, and society is essential for evaluating outcomes and designing optimal treatment plans. The authors aimed to elucidate specific rhinoplasty-related outcomes that are most important to patients, surgeons, and the general population. A cross-sectional survey comprising 11 rhinoplasty-specific characteristics, was distributed to patients, facial plastic surgeons, and the general population. Adult patients presenting for rhinoplasty consideration or follow-up after undergoing rhinoplasty were recruited. Characteristics rankings were compared between the 3 respondent groups using Spearman's rank correlation coefficient (ρ). Responses from 150 surgeons, 111 patients, and 102 lay individuals from the general population were included for analysis. When ranking rhinoplasty-specific characteristics in order of importance, patients and the general population ranked "ability to breathe through nose while awake" first and "overall appearance of nose" as second. Surgeons ranked "overall appearance of nose" first and "ability to breathe through nose while awake" second. There were strong correlations between patients' and surgeons' rankings (Spearman's ρ=0.836, P =0.002), between patients' and the general population's rankings (Spearman's ρ=0.773, P =0.007), and between surgeons' and the general population's rankings (Spearman's ρ=0.782, P =0.006). Our results highlight a significant correlation between characteristics of the "ideal" nose as determined by patients, surgeons, and the general population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Objective: Deformational Plagiocephaly (DP) is commonly treated with cranial orthosis, or helmet therapy. A large, national study on the impact of insurance status on helmet outcomes is lacking. We assessed treatment outcomes for helmet therapy based on insurance status., Design: This was a retrospective data analysis of patients referred to Cranial Technologies, Inc for helmet therapy between 2014-2020 across 21 states., Patients, Participants: There were a total of 211,417 patients referred for helmeting, of whom 141,513 received helmet therapy., Main Outcomes Measures: Multivariate regression was used to assess the relationship of insurance status with post-treatment residual flattening, measured by cephalic index (CI) and cranial vault asymmetry index (CVAI), and treating provider rating of success., Results: Patients with Medicaid were more likely to complete treatment with residual flattening measured by CI and CVAI when compared to patients with private insurance (OR: 1.58, CI: 1.51-1.65, p < 0.001 and OR: 1.21, CI: 1.15-1.28, p < 0.001, respectively). Providers of patients with Medicaid were more likely to give a low rating of success following treatment (OR: 3.25, CI: 2.70-3.92, p < 0.001)., Conclusions: Our study investigating the impact of insurance status on helmet therapy across 21 states found that patients with Medicaid were more likely to experience residual flattening and have lower provider-rated outcomes compared to those with commercial insurance. Given significant caregiver burden posed by helmet therapy, which requires frequent visits and consistent helmet use, caregivers of patients with Medicaid may require greater support to reduce outcome disparities observed here., Competing Interests: Declaration of Conflicting InterestsMr. Littlefield is the Chief Science and Technology Officer at Cranial Technologies, Inc., and he has a financial interest in Cranial Technologies, Inc. All other authors have no conflicts of interest relevant to this article to disclose.

Objectives: Off-label use of Ciprodex® (ciprofloxacin-dexamethasone: CPD), an antibiotic-steroid combination solution, in the airway has been reported by pediatric otolaryngologists with anecdotal success. We examined national trends regarding off-label CPD use including prevalence, common indications, prescriber patterns, adverse events, and accessibility., Methods: 15-item cross-sectional survey was distributed to American Society of Pediatric Otolaryngology members from January-April 2022. Univariate analyses were performed to compare responses for users of off-label CPD versus non-users. Ease of access was compared across geographies and practice types using multivariate logistic regressions., Results: Of the 163 complete responses (26.6% response rate), 156 (95.7%) reported using off-label CPD. Most common indications for off-label CPD were tracheal granulation (87.8%, n = 137) and choanal atresia (82.1%, n = 128). Ease of access was significantly increased in the Midwest (OR:18.79, 95%CI:3.63-1.24, p = 0.001) and West (OR:29.92, 95%CI:3.55-682.00, p = 0.006). Ease of access was significantly lower at tertiary referral centers (OR:0.11, 95%CI:0.01-0.64, p = 0.041) and private practices (OR:0.04, 95%CI:0.002-0.33, p = 0.009) compared to academic free-standing children's hospitals. Two-thirds of respondents reported feeling "Very Comfortable" with the safety profile of off-label CPD; 99.4% (n = 156) felt that the benefits outweighed the risks of off-label use. Seven respondents (4.5%) reported adverse events (e.g., local allergic reaction, cushingoid symptoms) from off-label use., Conclusions: Our findings (26.6% response rate) suggest that off-label CPD is commonly used by pediatric otolaryngologists, many of whom reported feeling that the benefits of off-label CPD outweigh the risks. Our results establish a baseline for future efforts to assess the efficacy and safety of off-label CPD and to improve its accessibility., Level of Evidence: V Laryngoscope, 134:2922-2930, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Genetic screens are valuable for identifying novel genes involved in the regulation of developmental processes. To identify genes associated with cell growth regulation in Drosophila melanogaster , a mutagenesis screen was performed. Undergraduate students participating in Fly-CURE phenotypically characterized the E.4.1 mutant which is associated with rough eyes and antennae overgrowth. Following complementation analysis and subsequent genomic sequencing, E.4.1 was identified as a novel mutant allele of GstE14 , a gene involved in ecdysone biosynthesis important for the timing of developmental events. The abnormal eye and antenna phenotypes observed resulting from the loss of GstE14 suggest its role in tissue growth., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Traditionally, otolaryngologists are taught that the defining clinical feature of a laryngeal cleft is aspiration. However, in a small subset of patients-even those with extensive clefts-the sole presenting feature may be airway obstruction. Here, we report two cases of type III laryngeal clefts that presented with upper airway obstruction without aspiration. The first patient was a 6-month-old male with history of tracheoesophageal fistula (TEF) who presented with noisy breathing, initially thought to be related to tracheomalacia. Polysomnogram (PSG) demonstrated moderate OSA and modified barium swallow (MBS) was negative for aspiration. In-office laryngoscopy was notable for a mismatch of tissue in the interarytenoid region. A type III laryngeal cleft was identified on bronchoscopy, and airway symptoms resolved after endoscopic repair. The second patient was a 4-year-old male with a diagnosis of asthma who presented with progressive exercise-induced stridor and airway obstruction. In-office flexible laryngoscopy revealed redundant tissue in the posterior glottis and MBS was negative for aspiration. He was found to have a type III laryngeal cleft on bronchoscopy and his stridor and upper airway obstruction resolved after endoscopic repair. While aspiration is the most common presenting symptom of a laryngeal cleft, it is important to consider that patients can have a cleft in the absence of dysphagia. Laryngeal cleft should be included in the differential diagnosis for patients with obstructive symptoms not explained by other etiologies and in those with suspicious features on flexible laryngoscopy. Laryngeal cleft repair is recommended to restore normal anatomy and relieve obstructive symptoms. Laryngoscope, 134:977-980, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Reconstruction for microtia decreased psychosocial morbidity; timely referral for surgery is crucial. We evaluated specialist referrals for microtia at a major academic medical center. Only one-half of patients were evaluated at any point by a reconstructive craniofacial surgeon. Patients followed early for audiologic concerns may not be receiving timely referred for reconstruction., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Synovial cysts are a common finding in degenerative spine disease, most frequently involving the facet joints of the lumbar spine. Synovial cysts are less common in the cervical spine and rarely involve the atlantoaxial junction., Observations: In this case report, the authors detail a unique presentation of a left atlantoaxial synovial cyst with large intracranial extension into the cerebellopontine angle causing progressive cranial nerve palsies resulting in tinnitus, vertigo, diminished hearing, gait imbalance, left trigeminal hypesthesia, left facial weakness, and dysarthria. The patient underwent a retromastoid craniectomy for resection of the synovial cyst, resulting in improvement and resolution of symptoms. Follow-up occurred at 6 weeks, 3 months, and 5 months postoperatively without recurrence on imaging., Lessons: The authors describe acute and long-term management of a unique presentation of an atlantoaxial synovial cyst including retromastoid craniectomy, intervals for follow-up for recurrence, and possible treatment options in cases of recurrence. A systematic literature review was also performed to explore all reported cases of craniocervical junction synovial cysts and subsequent surgical management.

With the increasing consolidation of physician practices, private equity (PE) firms have been playing a growing role in healthcare delivery and recently began entering the otolaryngology-head and neck surgery space. To date, no studies have examined the extent of PE investment in otolaryngology. We assessed trends and geographic distribution of US otolaryngology practices acquired by PE using Pitchbook (Seattle, WA), a comprehensive market database. From 2015 to 2021, 23 otolaryngology practices were acquired by PE. The number of PE acquisitions increased over time: 1 practice was acquired in 2015 versus 4 practices in 2019 versus 8 practices in 2021. Nearly half (43.5%, n = 10) of acquired practices were in the South Atlantic region. The median number of otolaryngologists at these practices was 5 (interquartile range: 3-7). As PE investment in otolaryngology continues to grow, further research is needed to assess its impact on clinical decision-making, healthcare costs, physician job satisfaction, clinical efficiency, and patient outcomes., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Mutant B.4.1 , generated via EMS mutagenesis in Drosophila melanogaster , was studied by undergraduate students participating in the Fly-CURE. After inducing genetically mosaic tissue in the adult eye, B.4.1 mutant tissue displays a robust increase in cell division and a rough appearance. Complementation mapping and sequence analysis identified a nonsense mutation in the gene CG1603 , which we named clifford ( cliff ) due to observed increases in red-pigmented mutant tissue compared to controls. cliff encodes a zinc finger-containing protein implicated in transcriptional control. RNAi knockdown of cliff similarly results in rough eyes, confirming a role for Cliff in eye development., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

Objective: To evaluate the 2020 to 2021 Otolaryngology residency application cycle in the context of recent trends., Study Design: Retrospective data analysis., Setting: Disruptions caused by the COVID-19 pandemic may significantly alter trends among residency applicants, especially in highly competitive and/or smaller specialties., Methods: Applicant and residency statistics from Electronic Residency Application Service (ERAS) and National Residency Matching Program (NRMP) were extracted from the 2016 to 2021 and 2011 to 2021, respectively. Trends in Otolaryngology-Head and Neck Surgery (OHNS) were compared to peer specialties (PS) including Dermatology, Neurological Surgery, Orthopedic Surgery, and Integrated Pathway for Plastic and Reconstructive Surgery (PRS). The ratio of the number of applicants per positions (APP) was used to reflect the degree of competition., Results: Between 2011 and 2021, the number of OHNS programs and positions expanded less than those of PS and General Surgery. The increase in the APP ratio was significantly greater for OHNS compared to those Dermatology, Orthopedic Surgery, General Surgery and all PGY1 residency positions for both US MD and all applicants ( P  < .01 for each). OHNS expansion of US MD ( P  = .046), but not all applicants ( P  = .169), outgrew that of Neurosurgery., Conclusion: The 2020 to 2021 cycle affected by the COVID-19 pandemic saw a continuation of the recent trend in the expanding OHNS applicant pool. OHNS remains one of the specialties with the highest APP ratio and has observed a significant growth compared to PS since 2018. Understanding and anticipating trends in residency application cycles is critical for designing processes to optimize the best fit between applicants and programs.

Objective(s): We aimed to develop a machine learning (ML) model to accurately predict the timing of oral squamous cell carcinoma (OSCC) recurrence across four 1-year intervals., Methods: Patients with surgically treated OSCC between 2012-2018 were retrospectively identified from the Yale-New Haven Health system tumor registry. Patients with known recurrence or minimum follow-up of 24 months from surgery were included. Patients were classified into one of five levels: four 1-year intervals and one level for no recurrence (within 4 years of surgery). Three sets of data inputs (comprehensive, feature selection, nomogram) were combined with 4 ML architectures (logistic regression, decision tree (DT), support vector machine (SVM), artificial neural network classifiers) yielding 12 models in total. Models were primarily evaluated using mean absolute error (MAE), lower values indicating better prediction of 1-year interval recurrence. Secondary outcomes included accuracy, weighted precision, and weighted recall., Results: 389 patients met inclusion criteria: 102 (26.2%) recurred within 48 months of surgery. Median follow-up time was 25 months (IQR: 15-37.5) for patients with recurrence and 44 months (IQR: 32-57) for patients without recurrence. MAE of 0.654% and 80.8% accuracy were achieved on a 15-variable feature selection input by 2 ML models: DT and SVM classifiers., Conclusions: To our knowledge, this is the first study to leverage multiclass ML models to predict time to OSCC recurrence. We developed a model using feature selection data input that reliably predicted recurrence within 1-year intervals. Precise modeling of recurrence timing has the potential to personalize surveillance protocols in the future to enhance early detection and reduce extraneous healthcare costs., Level of Evidence: 3 Laryngoscope, 133:1652-1659, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Given the increasing utilization of endoscopic surgery, particularly for airway stenosis management in the era of COVID-19 due to prolonged intubation, it is important to examine whether continuing antithrombotic therapy perioperatively influences bleeding complications. We examined the impact of perioperative antithrombotic use on postoperative bleeding complications following endoscopic airway surgery for laryngotracheal stenosis., Materials and Methods: Retrospective study from January 2016 to December 2021 of cases of patients ≥18 years who underwent endoscopic airway surgery for posterior glottic, subglottic, and tracheal stenosis at a single institution. Cases were excluded if they were an open airway surgery. The primary outcome was the occurrence of postoperative bleeding complications across cases of patients naive to and on baseline antithrombotic therapy, and those with preoperative continuation versus cessation of antithrombotic therapy., Results: 258 cases across 96 patients met inclusion criteria. Of these 258 cases, 43.4 % (n = 112) were performed for patients on baseline antithrombotic therapy and 56.6 % (n = 146) for those not on antithrombotic therapy. Likelihood of perioperative continuation of apixaban was 0.052 (odds ratio, 95 % Confidence Interval: 0.002-0.330, p < 0.001). Likelihood of perioperative continuation of aspirin was 9.87 (odds ratio, 95 % Confidence Interval: 2.32-43.0, p < 0.001). Two instances of postoperative bleeding were found: both in patients who were on aspirin without perioperative cessation for COVID-related coagulopathy., Conclusions: Our findings suggest that perioperative continuation of aspirin is relatively safe in the setting of endoscopic surgery for airway stenosis management. Prospective investigations to increase understanding of perioperative antithrombotics for COVID-related coagulopathy are warranted., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Objective(s): Coblation, or radiofrequency ablation, and pulsed-electron avalanche knife (PEAK) plasmablade are newer approaches for tonsillectomy that reduce exposure to thermal heat. This study aims to describe and compare adverse events related to these devices for tonsillectomy., Study Design: Retrospective cross-sectional study., Setting: The US Food and Drug Administration's Manufacture and User Facility Device Experience (MAUDE) database., Methods: The MAUDE database was queried for reports involving coblation devices and the PEAK plasmablade from 2011 to 2021. Data were extracted from reports pertaining to tonsillectomy with and without adenoidectomy., Results: There were 331 reported adverse events for coblation and 207 for the plasmablade. For coblation, 53 (16.0 %) of these involved patients and 278 (84.0 %) were device malfunctions. Similarly for the plasmablade, 22 (10.6 %) involved patients and 185 (89.4 %) were device malfunctions. The most frequent patient-related adverse event was burn injury, which was significantly more common with the plasmablade compared to coblation (77.3 % vs. 50.9 %, respectively, p = 0.042). For both the coblator and plasmablade, the most common device malfunction was intraoperative tip or wire damage (16.9 % vs. 27.0 %, respectively, p = 0.010). The Plasmablade tip caught fire in five reports (2.7 %) with one causing burn injury., Conclusions: While coblation devices and the plasmablade have demonstrated utility in tonsillectomy with or without adenoidectomy, they are associated with adverse events. Plasmablade use may require greater caution for intraoperative fires and patient burn injuries compared to coblation use. Interventions to improve physician comfort with these devices may help reduce adverse events and inform preoperative discussions with patients., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Absolute lymphocyte count (ALC) has been shown to be a prognostic indicator in other solid tumors. Given this, we aimed to evaluate the prognostic value of ALC in oral cavity squamous cell carcinoma (OSCC)., Methods: Using our institutional tumor registry data, we identified patients ≥18 years old who were diagnosed with OSCC between 2012 and 2018. Preoperative ALC values within 30 days of surgery were collected through retrospective chart review. American Joint Committee on Cancer, 7th-edition best stage was used to categorize cancers as early stage (stages 1 and 2) or late-stage (stages 3 and 4). Primary outcomes were likelihood of recurrence and survival rates after 3 years., Results: Of the 412 patients identified, 262 patients had available ALC data and met inclusion criteria. Early stage cancer patients who had lymphopenia did not have any significant difference in their rate of death ([OR], 1.71, CI: 0.54-5.45, p  = .36) or likelihood recurrence ([OR], 0.60, CI: 0.06-5.87, p  = .66) after controlling for age, tobacco use, alcohol use, positive margins, and adjuvant therapy. Late-stage cancer patients who had lymphopenia also showed no difference in their rate of death ([OR], 2.74, CI: 0.65-11.6, p  = .17) or likelihood of recurrence ([OR], 0.38, CI: 0.04-3.36, p  = .38)., Conclusions and Relevance: This study evaluates the prognostic value of ALC in oral cavity cancers. Our findings demonstrate that pretreatment ALC is not significantly associated with recurrence and survival outcomes patients with OSCC., Level of Evidence: III., Lay Summary: Absolute lymphocyte count (ALC) has been associated with prognosis in several cancers. We found that preoperative ALC was not associated with likelihood of survival or recurrence in patients with early stage or late-stage oral cavity cancer., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: Early exposure and mentorship in surgical specialties like otolaryngology - head and neck surgery are critical for medical students. This paper presents initiatives implemented at our institution to engage early-career medical students with the field., Methods: A hands-on laryngoscope workshop was organised, and a centralised online platform was created for research and mentorship opportunities using a collaborative project management tool. Both measures were advertised via e-mail to student interest groups and campus diversity groups. At the end of the workshop, participating students completed an online distributed survey., Results: Students' perception of their knowledge of airway anatomy and related clinical scenarios significantly improved after the laryngoscopy workshop ( p = 0.001 and p = 0.002, respectively). All attendees indicated that the workshop increased their comfort level with procedures and that they would recommend the workshop to colleagues. Nearly half of participants reported becoming 'very interested' in exploring otolaryngology - head and neck surgery through future elective courses., Conclusion: Implementation of such initiatives at other institutions can generate medical student interest and may improve diversity in otolaryngology - head and neck surgery.

Purpose: We examine prevalence, characteristics, quality of life (QOL) assessments, and long-term effects of interventions for laryngeal dysfunction after recovery from COVID-19 infection., Materials and Methods: 653 patients presenting to Yale's COVID clinic from April 2020 to August 2021 were identified retrospectively. Patients with PCR-positive COVID-19 who underwent evaluation by fellowship-trained laryngologists were included. Patient demographics, comorbidities, intubation/tracheostomy, strobolaryngoscopy, voice metrics, and management data were collected. Patient-reported QOL indices were Dyspnea Index (DI), Cough Severity Index (CSI), Voice Handicap Index-10 (VHI-10), Eating Assessment Tool-10 (EAT-10), and Reflux Symptom Index (RSI)., Results: 57 patients met inclusion criteria: 37 (64.9 %) were hospitalized for COVID-19 infection and 24 (42.1 %) required intubation. Mean duration between COVID-19 diagnosis and presentation to laryngology was significantly shorter for patients who were intubated compared to non-intubated (175 ± 98 days versus 256 ± 150 days, respectively, p = 0.025). Dysphonia was diagnosed in 40 (70.2 %) patients, dysphagia in 14 (25.0 %) patients, COVID-related laryngeal hypersensitivity in 13 (22.8 %), and laryngotracheal stenosis (LTS) in 10 (17.5 %) patients. Of the 17 patients who underwent voice therapy, 11 (64.7 %) reported improvement in their symptoms and 2 (11.8 %) patients reported resolution. VHI scores decreased for patients who reported symptom improvement. 7 (70 %) patients with LTS required >1 procedural intervention before symptom improvement. Improvement across QOL indices was seen in patients with LTS., Conclusions: Laryngeal dysfunction commonly presents and is persistent for months after recovery from COVID-19 in non-hospitalized and non-intubated patients. Voice therapy and procedural interventions have the potential to address post-COVID laryngeal dysfunction., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To perform a literature review on burnout prevalence, factors that affect burnout and well-being, and solutions to address burnout in otolaryngology-head and neck surgery (OTO-HNS) residents and residents in other surgical specialties., Data Sources: Ovid Medline, Embase, and article reference lists., Review Methods: A literature search was performed to identify articles on resident burnout, distress, wellness, well-being, and quality of life. Articles deemed outside the scope of the current work were excluded. Search was limited to the past 5 years., Conclusions: Moderate to high burnout has been reported in 35% to 86% of OTO-HNS residents. Among other surgical specialties, resident burnout ranges between 58% and 66% in plastics, 11% and 67% in neurosurgery, 38% and 68% in urology, and 31% and 56% in orthopedics. Highest burnout rates were seen in postgraduate year 2 residents. Factors significantly associated with burnout included hours worked (>80 h/wk), level of autonomy, exercise, and program support. Reported resident work hours have steadily increased: 8% of OTO-HNS residents in 2005 vs 26% in 2019 reported averaging >80 h/wk. Practical implications of resident burnout include decreased empathy, moral distress and injury, poor health, decreased quality of life, increased attrition, decreased desire to pursue fellowship, and increased likelihood of medical errors. Structured mentorship programs, wellness initiatives, and increased ancillary support have been associated with lower burnout rates and improvements in resident well-being across specialties., Implications for Practice: Addressing burnout, which is prevalent in OTO-HNS residents, is critical to improving patient care and physician well-being. Surgical specialties can share strategies to effectively address resident burnout through institutional interventions, which can be essential quality improvement initiatives, to promote well-being., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Deformational plagiocephaly and brachycephaly, or abnormal flattening of the infant skull due to external forces, are often managed with orthotic helmet therapy. Although helmet therapy is widely used, the factors that predict poor outcomes are not well characterized. In this study of over 140,000 patients who received helmet therapy, older age and greater severity at presentation, and noncompliance with treatment were each independently associated with worse craniometric and provider-reported outcomes. Each additional point of cranial vault asymmetry index or cephalic index at a presentation is associated with an increased likelihood of residual brachycephaly at completion [odds ratio (OR): 1.067; 95% Cl: 1.058-1.075; P <0.0001 and OR: 2.043; 95% CI: 2.021-2.065; P <0.0001, respectively], whereas each additional point of cranial vault asymmetry index at a presentation associated with increased likelihood of residual asymmetry at completion (OR: 2.148; 95% Cl: 2.118-2.179; P <0.0001). Patients were more likely to have residual brachycephaly or asymmetry with increasing age at treatment initiation (OR: 1.562; 95% CI: 1.524-1.600; P <0.0001 and OR: 1.673; 95% Cl: 1.634-1.713; P <0.0001, respectively, for each additional month of age at initiation). These results highlight a need for prompt referral for helmeting, especially in cases with severe features or when patients present late to care. Potentially modifiable factors are age at helmeting and compliance with treatment protocols, and consideration of these factors may be important for achieving success in some cases., Competing Interests: T.R.L. is the Chief Science and Technology Officer at Cranial Technologies Inc., and he has a financial interest in Cranial Technologies Inc. The remaining authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Objectives: The traditional endoscopic techniques for surgical management of laryngeal clefts are carbon dioxide (CO 2 ) laser or microlaryngeal instruments (cold steel). This study compares the functional efficacy and safety of coblation, or "cold" radiofrequency ablation, to traditional approaches for endoscopic laryngeal cleft repair., Methods: Patients who underwent endoscopic laryngeal cleft repair with CO 2 laser, cold steel, or coblator at two tertiary academic centers from 2015 to 2021 were retrospectively identified. The primary outcome studied was swallowing function: pre- and postoperative swallow studies were scored according to the International Dysphagia Diet Standardization Initiative with higher scores indicating worse swallow function. Secondary outcomes included surgical complications and rates of dehiscence., Results: Of the 53 patients included, 14 underwent repair with CO 2 laser, 23 with cold steel, and 16 with the coblator. Mean age at surgery was 2.2 ± 1.1 years for the laser group, 4.3 ± 4.0 years for cold steel, and 1.9 ± 1.4 years for the coblator group. In the laser group, 100% of clefts were type I; for the cold steel group, 82.6% of clefts were type I and 17.4% were type II; for the coblator group, 93.8% of clefts were type I and 6.3% were type II. Pre- and postoperative swallow study scores were 6.3 ± 2.8 and 4.3 ± 3.2, respectively, (p = 0.001) for the laser group, 6.9 ± 2.8 and 5.3 ± 3.1 (p = 0.071) for the cold steel group, and 7.5 ± 1.5 and 4.0 ± 2.9 (p < 0.001) for the coblator group. Mean change in swallow study scores were similar across the three groups (p = 0.212). No patients experienced postoperative dehiscence at the surgical site or complications; no revisions were required., Conclusions: Cleft repair with the novel coblation technique showed significant improvements in swallow study scores without any occurrences of postoperative dehiscence or revisions. Coblation is a safe and efficacious approach for laryngeal cleft repair., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Facial trauma accounts for over 3 million emergency room encounters each year in the United States and places significant financial burden on the health care system and surgeons. However, data on facial trauma call practices among plastic surgeons are lacking. We surveyed members of the American Society of Maxillofacial Surgeons (ASMS) regarding their experience with facial trauma call. A 27-question online survey was distributed through e-mail to ASMS members. Forty-five ASMS members completed the survey, of whom 64% were required to take facial trauma call and 44% were compensated for call. Respondents in the North-East were less likely [odds ratio (OR): 0.234, confidence interval (CI), 0.054-1.015; P =0.052] to be compensated for taking call, whereas those who worked at level 1 trauma centers were more likely odds ratio: 5.42, CI, 0.892-32.89; P =0.066) to be compensated. Surgeons required to take facial trauma call were 4.646 (CI, 1.203-17.944; P =0.026) times more likely to take call ≥5 days per month. These results highlight a relatively low proportion of plastic surgeons receiving additional compensation for facial trauma call while work at a level 1 trauma center was associated with higher likelihood of compensation. Surgeons in the Northeast may be compensated less frequently than other regions. Plastic surgeons should be aware of these trends, as they decide how to incorporate facial trauma call into their practice., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Introduction: Recent data suggest basophils can adopt an atypical appearance in myeloid disorders including myeloproliferative neoplasms (MPNs) and myeloproliferative/myelodysplastic disease. We hypothesized that automated analysers may not accurately quantitate basophils in myeloid neoplasms based on scatter properties. This study examined basophil counts and properties in myeloid disorders by automated cell analyser, manual differential, and flow cytometry., Methods: Patients with myeloid neoplasms and control patients with no myeloid disorder diagnosis at a tertiary care centre were identified. Basophil percentage was compared for automated analyser counts (Sysmex XN9000), manual differential, and flow cytometry. Basophil scatter properties in MPNs were examined using flow cytometry., Results: Thirty-one patients with myeloid neoplasms were included: 58% were male, mean age was 70.2 (±20.7) years, 32% had a diagnosis of chronic myeloid leukaemia with the remaining patients divided among various other forms of myeloid disease (including: essential thrombocythemia, polycythemia vera, unclassifiable MPN, myelodysplastic syndromes). For these patients, mean basophil percentage by automated analyser was significantly lower than manual differential (2.7 ± 2.9 vs. 7.1 ± 4.6, respectively, p < 0.001). No significant difference was found between automated versus manual differential for basophils in control subjects (p = 0.373). For myeloid neoplasm patients, mean basophil percentage was not significantly different between manual differential and flow cytometry (p = 0.116); mean basophil percentage by automated analyser was significantly lower than flow cytometry (2.7 ± 2.9 vs. 5.3 ± 3.7, respectively, p = 0.003)., Conclusion: Automated analysers underestimate basophil counts in patients with myeloid neoplasms. Manual differential and flow cytometry are recommended for more accurate quantitation and characterization of aberrant basophils., (© 2022 John Wiley & Sons Ltd.)

Objectives: Reconstructive surgery may result in prolonged postoperative recovery, especially in frail patients, which in turn may impact delivery of adjuvant therapy. To date, no studies have investigated potential associations between frailty and adjuvant treatment delivery after reconstructive surgery. We examine the impact of frailty on time to initiation, duration, and completion of adjuvant treatment after reconstructive surgery for head and neck cancers (HNCs)., Methods: A retrospective review of patients who underwent free flap reconstruction for HNC at a single institution from 2015 to 2021 and received adjuvant radiation was performed. Frailty was assessed using two independent scales: the 11-item modified frailty index (mFI) score and binary Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator. Timely adjuvant initiation (within six weeks of surgery), duration of adjuvant treatment, and completion were compared between frail and non-frail patients., Results: Of the 163 patients included for analysis, 52 (31.9%) were identified as frail by the ACG indicator and 24 (14.7%) were identified as frail with an mFI score ≥ 3. Frail patients (mFI score ≥ 3) were significantly less likely than non-frail patients to initiate adjuvant treatment within six weeks (OR:0.21, CI:0.04-0.85, p = 0.046). Frailty designated by either frailty scale was not significantly associated with adjuvant treatment duration. Likelihood of adjuvant treatment completion was significantly lower for frail compared to non-frail patients by both scales: ACG indicator (OR 0.02, CI:9.05 × 10 -4 -0.25, p = 0.007) and mFI score ≥ 3 (OR:0.01, CI:6.85 × 10 -4 -0.13, p = 0.007)., Conclusions: Frailty is associated with decreased likelihood of timely adjuvant treatment initiation and completion in patients with HNCs after free flap reconstruction., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The basement membrane (BM) - a specialized sheet of extracellular matrix present at the basal side of epithelial cells - is critical for the establishment and maintenance of epithelial tissue morphology and organ morphogenesis. Moreover, the BM is essential for tissue modeling, serving as a signaling platform, and providing external forces to shape tissues and organs. Despite the many important roles that the BM plays during normal development and pathological conditions, the biological pathways controlling the intracellular trafficking of BM-containing vesicles and how basal secretion leads to the polarized deposition of BM proteins are poorly understood. The follicular epithelium of the Drosophila ovary is an excellent model system to study the basal deposition of BM membrane proteins, as it produces and secretes all major components of the BM. Confocal and super-resolution imaging combined with image processing in fixed tissues allows for the identification and characterization of cellular factors specifically involved in the intracellular trafficking and deposition of BM proteins. This article presents a detailed protocol for staining and imaging BM-containing vesicles and deposited BM using endogenously tagged proteins in the follicular epithelium of the Drosophila ovary. This protocol can be applied to address both qualitative and quantitative questions and it was developed to accommodate high-throughput screening, allowing for the rapid and efficient identification of factors involved in the polarized intracellular trafficking and secretion of vesicles during epithelial tissue development.

Background: The coronavirus disease 2019 pandemic created challenges in surgical education that expedited the development of virtual learning. Virtual rotations have been one such solution. However, they require co-ordination and technological equipment to create a meaningful, interactive experience for students., Methods: Various otolaryngology surgical procedures were live-streamed during a two-week virtual rotation for medical students. A mobile audiovisual cart comprising a computer mounted with a webcam and microphone/speaker were utilised to live-stream from four sources: video-assisted telescope operating monitor ('VITOM') exoscope, microscope, endoscope and room camera. A dedicated faculty member, who was not the operating surgeon, was present to facilitate students' understanding of the procedure., Conclusion: A wide breadth of otolaryngology surgical procedures were live-streamed via a mobile audiovisual computer, including views of the room, endoscopic views, microscopic views and open views via an exoscope (video-assisted telescope operating monitor). This virtual rotation set-up, along with the dedicated faculty facilitator, reduced the burden on the operating surgeon and enhanced students' learning experience.

Myocarditis has a wide array of clinical presentations ranging from asymptomatic to sudden cardiac death. Pediatric myocarditis is a rare disease, with an estimated annual incidence of 1 to 2 per 100,000 children though its true prevalence remains unknown due to its variable and often subclinical presentation. The diagnosis of myocarditis is challenging in the era of COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C), which can have overlapping clinical conundrum. Here, we present a case of a 17-year-old male presenting with chest tightness, shortness of breath, and electrocardiogram (EKG) findings concerning for myocardial injury along with elevated inflammatory markers such as D-dimer, ESR (Erythrocyte Sedimentation Rate), and CRP (C-Reactive Protein). We discuss the key elements of our clinical experience with this case and review the literature for pediatric myocarditis, with a focus on differentiating it from MIS-C in the current COVID-19 pandemic era., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Hemali P. Shah et al.)

Background: In this study, we describe a technique of optimizing the accuracy of frameless deep brain stimulation (DBS) lead placement through the use of a cannula poised at the entry to predict the location of the fully inserted device. This allows real-time correction of error prior to violation of the deep gray matter., Methods: We prospectively gathered data on radial error during the operative placements of 40 leads in 28 patients using frameless fiducial-less DBS surgery. Once the Nexframe had been aligned to target, a cannula was inserted through the center channel of the BenGun until it traversed the pial surface and a low-dose O-arm spin was obtained. Using 2 points along the length of the imaged cannula, a trajectory line was projected to target depth. If lead location could be improved, the cannula was inserted through an alternate track in the BenGun down to target depth. After intraoperative microelectrode recording and clinical assessment, another O-arm spin was obtained to compare the location of the inserted lead with the location predicted by the poised cannula., Results: The poised cannula projection and the actual implant had a mean radial discrepancy of 0.75 ± 0.64 mm. The poised cannula projection identified potentially clinically significant errors (avg 2.07 ± 0.73 mm) in 33% of cases, which were reduced to a radial error of 1.33 ± 0.66 mm (p = 0.02) after correction using an alternative BenGun track. The final target to implant error for all 40 leads was 1.20 ± 0.52 mm with only 2.5% of errors being >2.5 mm., Conclusion: The poised cannula technique results in a reduction of large errors (>2.5 mm), resulting in a decline in these errors to 2.5% of implants as compared to 17% in our previous publication using the fiducial-less method and 4% using fiducial-based methods of DBS lead placement., (© 2021 S. Karger AG, Basel.)

Here, we present a young asymptomatic male patient incidentally diagnosed to have aortic regurgitation (AR). The patient had a history of a blunt trauma to the thorax two years back but did never have any symptoms. Transthoracic echocardiography showed a moderately dilated left ventricle with normal systolic function and severe AR with normal nondilated aortic root and tri-leaflet aortic valve. To diagnose the etiology of the AR, a transesophageal echocardiogram (TEE) was done, which revealed a perforation in the nonadjacent leaflet (NAL) and confirmed severe AR with two AR jets being clearly visualized, one through the point of incomplete coaptation and other one through the perforated area in the NAL. The patient was treated with aortic valve replacement and was doing well on follow-up., (© 2020 Wiley Periodicals LLC.)

Mycobacterium fortuitum is a rare, opportunistic pathogen most frequently contracted through contact with a contaminated source. An immunocompetent 26-year-old female patient presented to our institution with an infected lumboperitoneal (LP) shunt presenting as continued nonhealing wounds. After multiple debridements, shunt revisions, and wound closure failures, infectious disease specialists were consulted. The wound cultures returned positive for M. fortuitum and the shunt was removed. Cerebrospinal fluid studies revealed significant pleocytosis with normal opening pressure, and the patient was diagnosed as having secondary meningitis. After shunt removal, the patient was treated with intravenous and oral antibiotics, resulting in infection resolution. Five months later, a new LP shunt was placed without infection recurrence. Although M. fortuitum was previously reported in neurosurgical patients with ventriculoperitoneal shunts, which are summarized here, to date this is the first case in the literature of M . fortuitum meningitis from an LP shunt. This case demonstrates the importance of clinicians considering uncommon and slow-growing pathogens, as well as consulting infectious disease specialists for patients with persistent, unexplained infections.

Introduction: Spinal subdural hematomas are rare, disabling hemorrhages. Ankylosing spondylitis (AS) is a relatively common inflammatory condition of the spine that can progress to a fragile, unstable fusion vulnerable to fracture. While spinal epidural hematomas have been described, subdural hematomas to date have not been reported in AS. In this report, we describe the unique case of a patient on warfarin with AS who developed a spinal subdural hematoma and fracture in the absence of trauma. We then discuss the pathogenesis, presentation, prognosis, and management strategies for this unique diagnosis., Case Presentation: A 60-year-old man with recent AS diagnosis and atrial fibrillation on warfarin presented with 96 h of low back pain and 24 h of leg weakness and urinary retention. CT imaging revealed a bamboo spine and fracture of the posterior elements at L4, while MR revealed a hematoma with thecal sac compression. The warfarin was reversed and the patient taken to the operating room; on laminectomy, however, no hematoma was encountered. The patient then underwent intraoperative ultrasound, durotomy, and evacuation of a thick subdural hematoma, followed by posterior fusion., Discussion: This case represents the first report of an AS patient who developed a subdural hematoma requiring evacuation. Although rare, the clinician should maintain a broad differential and be familiar with this unique pathology, particularly in high-risk patients, such as those with suspected fractures or on warfarin. In patients with back pain and myelopathic symptoms, rapid diagnosis followed by prompt evacuation allows for the best opportunity for neurologic recovery., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

Using a recently discovered precatalyst, the first Pd-catalyzed Suzuki-Miyaura reactions using aryl sulfamates that occur at room temperature are reported. In complementary work, it is demonstrated that a related precatalyst can facilitate the coupling of aryl silanolates, which are less toxic and reactive nucleophiles than boronic acids with aryl chlorides. By combining our results using modern electrophiles and nucleophiles, the first Hiyama-Denmark reactions using aryl sulfamates are reported.

Complexes of the type (η(3)-allyl)Pd(L)(Cl) and (η(3)-indenyl)Pd(L)(Cl) are highly active precatalysts for the Suzuki-Miyaura reaction. Even though allyl and indenyl ligands are similar to cyclopentadienyl (Cp) ligands, there have been no detailed comparative studies exploring the activity of precatalysts of the type (η(5)-Cp)Pd(L)(Cl) for Suzuki-Miyaura reactions. Here, we compare the catalytic activity of (η(5)-Cp)Pd(IPr)(Cl) (IPr = 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene, Cp) with two commercially available catalysts (η(3)-cinnamyl)Pd(IPr)(Cl) (Cin) and (η(3)-1-t-Bu-indenyl)Pd(IPr)(Cl) ( (tBu) Ind). We show that Cp gives slightly better catalytic activity than Cin, but significantly inferior activity than (tBu) Ind. This order of activity is rationalized by comparing the rates at which the precatalysts are activated to the monoligated Pd(0) active species along with the tendency of the starting precatalysts to comproportionate with monoligated Pd(0) to form inactive Pd(I) dimers. As part of this work the Cp supported Pd(I) dimer (μ-Cp)(μ-Cl)Pd2(IPr)2 (Cp (Dim) ) was synthesized and crystallographically characterized. It does not readily disproportionate to form monoligated Pd(0) and consequently Cp (Dim) is a poor catalyst for the Suzuki-Miyaura reaction.

Ex vivo differentiation of myeloid cells begins with an enriched population of bone marrow-derived hematopoietic stem cells generated by lineage depletion and/or positive selection for CD34(+) antigen (human) or Sca-1(+) (mouse) cells, which are then expanded and subsequently induced in vitro in a process that recapitulates normal myeloid development. Myeloid cell lines include two human leukemic cell lines, NB-4 and HL-60, which have been demonstrated to undergo retinoic acid-induced myeloid development; however, both cell lines exhibit defects in the up-regulation of late-expressed neutrophil-specific genes. Multiple murine factor-dependent cell models of myelopoiesis are also available that express the full range of neutrophil maturation markers, including: 32Dcl3 cells, which undergo G-CSF-induced myeloid maturation; EML/EPRO cells, which develop into mature neutrophils in response to cytokines and retinoic acid; and ER-Hoxb8 cells, which undergo myeloid maturation upon removal of estradiol in the maintenance medium. In this unit, the induction of myeloid maturation in each of these model systems is described, including their differentiation to either neutrophils or macrophages, if applicable. Commonly used techniques to test for myeloid characteristics of developing cells are also described, including flow cytometry and real time RT-PCR., (Copyright © 2014 John Wiley & Sons, Inc.)

The lactonase enzyme (AiiA) produced by Bacillus thuringiensis serves to degrade autoinducer-1 (AI-1) signaling molecules in what is an evolved mechanism by which to compete with other bacteria. Bioassays have been previously performed to determine whether the AI-1 aliphatic tail lengths have any effect on AiiA's bioactivity, however, data to date are conflicting. Additionally, specific residue contributions to the catalytic activity of AiiA provide for some interesting questions. For example, it has been proposed that Y194 serves to provide an oxyanion hole to AI-1 which is curious given the fact the substrate spans two Zn(2+) ions. These ions might conceivably provide enough charge to promote both ligand stability and the carbonyl activation necessary to drive a nucleophilic attack. To investigate these questions, multiple molecular dynamics simulations were performed across a family of seven acylated homoserine lactones (AHL) along with their associated intermediate and product states. Distance analyses and interaction energy analyses were performed to investigate current bioassay data. Our simulations are consistent with experimental studies showing that AiiA degrades AHLs in a tail length independent manner. However, the presence of the tail is required for activity. Also, the putative oxyanion hole function of Y194 toward the substrate is not observed in any of the reactant or product state simulation trajectories, but does seem to show efficacy in stabilizing the intermediate state. Last, we argue through ionization state analyses, that the proton shuttling necessary for catalytic activity might be mediated by both water and substrate-based intra-molecular proton transfer. Based on this argument, an alternate catalytic mechanism is proposed.

The effects of the halogenated aromatic amino acid 3,5-dibromo-D: -tyrosine (3,5-DBr-D: -Tyr) were studied in rat models of stroke and epileptic seizures caused by middle cerebral artery occlusion (MCAo) through respective intracerebral injection of endothelin-1 (ET-1) and intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ). 3,5-DBr-D: -Tyr was administered as three bolus injections (30 or 90 mg/kg, i.p.) starting at 30, 90, and 180 min after ET-1 administration or as a single bolus (30 mg/kg, i.p.) 15 min prior to PTZ administration. Neurological deficits and infarct volume were estimated 3 days after ET-1 administration and seizure score was assessed during the first 20 min after PTZ administration. The safety of 3,5-DBr-D: -Tyr was evaluated in control animals using telemetry to measure cardiovascular parameters and immunostaining to assess the level of activated caspase-3. 3,5-DBr-D: -Tyr significantly improved neurological function and reduced infarct volume in the brain even when the treatment was initiated 3 h after the onset of MCAo. 3,5-DBr-D: -Tyr significantly depressed PTZ-induced seizures. 3,5-DBr-D: -Tyr did not cause significant changes in arterial blood pressure, heart rate and spontaneous locomotor activity, nor did it increase the number of activated caspase-3 positive cells in the brain. We conclude that 3,5-DBr-D: -Tyr, by alleviating the deleterious effects of MCAo and PTZ in rats with no obvious intrinsic effects on cardiovascular parameters and neurodegeneration, exhibits promising potential as a novel therapeutic direction for stroke and seizures.

Epidemiological studies indicate that parental smoking increases the risk for smoking in children. However, the underlying mechanisms by which parental smoking increases the risk for smoking are not known. The aim of these studies was to investigate if preadolescent tobacco smoke exposure, postnatal days 21-35, affects the rewarding effects of nicotine and nicotine withdrawal in adult rats. The rewarding effects of nicotine were investigated with the conditioned place preference procedure. Nicotine withdrawal was investigated with the conditioned place aversion procedure and intracranial self-stimulation (ICSS). Elevations in brain reward thresholds in the ICSS paradigm reflect a dysphoric state. Plasma nicotine and cotinine levels in the preadolescent rats immediately after smoke exposure were 188 ng/ml and 716 ng/ml, respectively. Preadolescent tobacco smoke exposure led to the development of nicotine dependence as indicated by an increased number of mecamylamine-precipitated somatic withdrawal signs in the preadolescent tobacco smoke exposed rats compared to the control rats. Nicotine induced a similar place preference in adult rats that had been exposed to tobacco smoke or air during preadolescence. Furthermore, mecamylamine induced place aversion in nicotine dependent rats but there was no effect of preadolescent tobacco smoke exposure. Finally, preadolescent tobacco smoke exposure did not affect the elevations in brain reward thresholds associated with precipitated or spontaneous nicotine withdrawal. These studies indicate that passive exposure to tobacco smoke during preadolescence leads to the development of nicotine dependence but preadolescent tobacco smoke exposure does not seem to affect the rewarding effects of nicotine or nicotine withdrawal in adulthood., (Published by Elsevier Inc.)