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Considering limited data exploring reimbursement trends at the subspecialty level within head and neck surgical oncology, we sought to characterize these trends for head and neck-specific codes from 2000 to 2020.Using the Centers for Medicare and Medicaid Services' Physician Fee Schedule Look-Up Tool, reimbursement data, adjusted to 2020 U.S. dollars, for 37 head and neck surgical oncologic procedure codes were collected from 2000 to 2020.From 2000 to 2020, despite gross reimbursement for all head and neck procedures increasing by 23.2%, when adjusted for inflation, physician reimbursement decreased by 19.4%. Only 4 of 37 examined codes increased in net reimbursement over the study period.Medicare reimbursement for the most common head and neck oncologic procedure codes decreased from 2000 to 2020. Further research is necessary to explore the implications of these trends on the delivery of patient care.

Tandem mass tag (TMT)-based proteomics facilitate multiplexing in mass spectrometry (MS)-based quantification and identification of proteins and their post-translational modifications. The use of TMT isobaric tags can enable multiplexing of up to 18 samples using commercially available kits. A single TMT experiment can quantify proteome, serine, threonine phosphorylation, and tyrosine phosphorylation. Of note, tyrosine phosphorylation is of low abundance, and identification/quantification can be improved using two complementary strategies. First, by employing SH2 superbinder which increases the number of identified sites. The SH2 Superbinder is more cost-effective than the commonly used phosphotyrosine antibodies. Second, by employing phosphotyrosine booster strategy, a pervanadate-treated channel to boost the signal of low-abundant phosphotyrosine. Noteworthy, pervanadate boost increases the likelihood of low abundant peptide to be selected for MS2, and facilitating the detection of > 6000 proteins, 10,000 unique pS/T and 1000 unique pY sites.

Recent years have seen increase in individuals pursuing postgraduate fellowships in head and neck (HN) surgery. This has presented concerns about insufficient jobs where graduates can apply their scope of specialized training.Data was collected in two manners- a survey and a manual online search of American Head and Neck Society (AHNS) fellowship graduates. A 25-question survey was sent in 2021 to approximately 400 HN fellows who graduated between 2010 and 2020. The AHNS list of graduates from the same years were searched online to collect information including gender, graduation year, fellowship training, and current job practice.Of the 78 survey responses, 64.1 % were male and 34.6 % female. 96.2 % reported ablative, 84.6 % microvascular, and 82.1 % TORS training. Mean number of interviews was 4 with most interviewing during the 3rd quarter (January to March). Majority reported being in academic and university-based practices (79.6 %). Online search was done on 393 graduates. Since 2010 the number of graduates almost doubled. There was a statistically significant increase in females by year (p = 0.022). There was a significant decrease (p = 0.022) in graduates with additional fellowship training from that of their AHNS fellowship. There was also a statistically significant increase in graduates being in academic practices (p = 0.022).Despite growing numbers, there appears to be more graduates entering an academic practice, although the definition of an academic HN practice may be evolving. These results provide guidance on how to approach the job search in a select market.II.

The zinc–nickel single-flow battery is a new and special type of flow battery with a number of promising features, such as membrane free and high scalability, and thus has attracted substantial interests in recent years. However, the cyclability of alkaline zinc cells is rather poor, with sharpened capacity degradation resulted from undesirable zinc deposition formation. Yet, little has been done so far to investigate how to effectively and reliably manage this new type of battery. In this article, an open-circuit-voltage estimator based online joint estimation of both the state of charge (SoC) and the state of health (SoH) is proposed. A second-order equivalent circuit model is applied to improve the accuracy. Meanwhile, an extended Kalman filter with reduced state dimension is formulated to estimate the SoC assisted with the proposed estimator, which solves the increased complexity issue in a higher order model. An SoH indicator is then derived from capacity estimate and employed to determine the time for reconditioning maintenance, which is a key stage to update capacity and prolong service life. The method is finally applied to a bench-scale cell demonstrator, and the experimental results confirm the efficacy of the proposed method.

To analyze the prognostic significance of microscopic vs macroscopic extranodal extension and to assess the impact of chemoradiation on overall survival among patients with oral cavity squamous cell carcinoma and varying degrees of extranodal extension.Utilizing the National Cancer Database, we performed a retrospective cohort study of 7975 patients with oral cavity squamous cell carcinoma and varying degrees of extranodal extension who underwent primary surgical intervention. Propensity-score matched models following Cox regression analyses allowed us to assess the impact of adjuvant radiation alone vs adjuvant chemoradiation on overall survival in patients with microscopic extranodal extension and macroscopic extranodal extension.7975 patients with oral cavity squamous cell carcinoma were included in the final analysis. Within this cohort, 25.4% had microscopic extranodal extension and 5.2% had macroscopic extranodal extension. On univariate analysis, we found that microscopic and macroscopic extranodal extension were associated with decreased overall survival when compared to those with positive nodes without extranodal extension (HR = 1.67; 95% CI 1.56, 1.79 and HR = 1.88; 95% CI 1.66, 2.14, respectively). On multivariate analysis after propensity-score matching, we found no significant difference in overall survival in patients who received adjuvant radiation alone vs. adjuvant chemoradiation for both microscopic and macroscopic extranodal extension.Our data suggest that microscopic extranodal extension in oral cavity squamous cell carcinoma is associated with worse overall survival than patients without extranodal extension following primary surgical intervention with neck dissection. The results of this study also suggest that the addition of chemotherapy to adjuvant radiation may not provide a significant survival benefit in patients with oral cavity squamous cell carcinoma with microscopic and macroscopic extranodal extension. Comprehensive assessment of the benefits of adjuvant chemoradiation in the setting of microscopic vs macroscopic extranodal extension would need to be studied in a randomized controlled trial.

Primary site is considered an important prognostic factor for cutaneous malignant melanoma (CMM); however, opinions vary regarding its influence on survival. This study compares overall survival between head and neck melanoma (HNM) and melanoma of other regions (MOR), as well as between melanoma of the scalp and neck (MSN) and melanoma of other head regions (MOHR).Level III retrospective cohort study.Patients from Commission on Cancer-accredited cancer programs affiliated to the National Cancer Database (NCDB).Patients with HNM (MSN and MOHR included) and MOR, stages I to IV (n = 39,754), and their linked survival data using the NCDB were identified. Survival was analyzed using propensity score matching methods.After matching using propensity scores, allowing this observational study to mimic a randomized controlled trial, subjects with HNM showed a 22% increased mortality when compared to MOR (Patients with HNM showed a higher mortality when compared to MOR. The risk of death of primary sites within the head and neck varies over time, showing a higher risk of mortality for scalp and neck during the first 3.5 years of follow-up. This increased risk was not evident after the 3.5-year threshold. Further research is needed to evaluate additional patient factors or differences in treatment approaches.

The incidence of p16+ oropharyngeal squamous cell carcinoma (OPSCC) has been increasing. The notion that p16+ OPSCC has a propensity for atypical and disseminating metastasis has gained traction. We compared treatment failure patterns in p16+ and p16- OPSCC and evaluated survival impact.Retrospective analysis of patients with recurrent/metastatic OPSCC disease between 1/2009 and 12/2019.Thirty-eight p16+ and 36 p16- patients were identified. Three distinct failure patterns (distant vs. locoregional, atypical vs. typical, and disseminating vs. non-disseminating) were studied. No significant differences were found between p16+ and p16- patients. Multivariate analysis showed p16 status was an independent prognostic biomarker; p16+ patients have a favorable overall survival compared to p16- patients (HR 0.34, 95% CI 0.16-0.77;We challenge the view that p16+ OPSCC exhibits a distinctive treatment failure pattern and showed that p16 status impacts patient survival independent of disease progression.

Objective: The objective of this study is to investigate the safety, efficacy, and potential cost-savings of the outpatient parotidectomy procedure. Methods: This is a retrospective chart review of all patients who underwent a parotidectomy at a large academic center from 2015 through 2019 including demographic data, postoperative complications, drain placement, readmission, and financial cost. A comparison was performed between patients who underwent an outpatient vs inpatient parotidectomy. Results: A total of 335 patients underwent parotidectomy (136 outpatient; 199 inpatient). Comparison of patient demographics, common comorbidities, tumor size, tumor type, postoperative complications, and readmission rate was similar between the inpatient and outpatient cohorts. The overall mean cost difference between inpatient parotidectomy and outpatient parotidectomy for all years was $1528.58 (95%CI: $1139-$1916). Conclusion: The outpatient parotidectomy procedure has a comparable safety profile to the inpatient procedure while providing a significant cost-savings benefit.

PURPOSE: Human papilloma virus–positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), diagnosed with p16 immunohistochemistry, is associated with favorable prognosis; however, this connection was established using European American (EA)–skewed populations. The impact of p16/human papillomavirus status on outcomes in African American (AA) OPSCC patients remains to be settled. In this study, we determine the association between cancer disparity and p16 status in an OPSCC cohort controlling for time to treatment initiation (TTI), a surrogate for medical care access. MATERIALS AND METHODS: We analyzed data from all patients diagnosed with OPSCC (N = 440) between 2010 and 2017, who received treatment at our academic medical center. Associations between age, disease stage, sex, p16 status, race, TTI, and overall survival (OS) were investigated. RESULTS: TTI was similar between AA and EA OPSCC patients in our p16+ ( P = .291) or p16− ( P = .715) cohorts. Among p16+ OPSCC patients, the median OS was > 8.65 years for EA patients compared with 5.038 years (95% CI, 2.019 to 5.30; P = .003, log-rank) for AA patients. For p16− patients, the median OS was 5.74 years (95% CI, 3.32 to 6.99) for EA patients and 1.85 years (95% CI, 0.978 to 4.50; P = .03, log-rank) for AA patients. Multivariate Cox regression analysis showed that race was an independent prognostic biomarker and the most impactful co-variate for OS (hazard ratio, 0.40; 95% CI, 0.00 to 0.69; P = .001). CONCLUSION: Our work showed that AAs with p16+ OPSCC have surprisingly poor clinical outcomes and are thus poor candidates for treatment de-escalation regimens. Caution should be exercised when extending clinical guidelines based on EA-majority studies to non-EA populations.

BACKGROUND: Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue. OBJECTIVE: To develop and evaluate a novel, biologic antimicrobial coating for medical implants. METHODS: Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per a protocol developed by our group. Sheets were incubated in antibiotic solution (gentamicin or moxifloxacin) overnight, and in vitro activity was assessed with five-day diffusion assays against Pseudomonas aeruginosa. Antibiotic release over time from gentamicin-infused sheets was determined using in vitro elution and high performance liquid chromatography (HPLC). RESULTS: Collagen-heparin-antibiotic sheets demonstrated larger growth inhibition zones against P. aeruginosa compared to collagen-antibiotic alone sheets. This activity persisted for five days and was not impacted by rinsing sheets prior to evaluation. Rinsed collagen-antibiotic sheets did not produce any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was gradual and remained above the minimal inhibitory concentration for gentamicin-sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic load within 24 hours. Overall, heparin-associated sheets demonstrated larger inhibition zones against P. aeruginosa and prolonged elution profile via HPLC. CONCLUSION: We developed a novel, local antibiotic delivery system that could be used to coat medical implants/hardware in the future and reduce post-operative infections.

e18780 Background: Patients with hematologic malignancies have a lower vaccine response and higher rates for SARS CoV-2 morbidity and mortality. We present preliminary data focusing on humoral vaccine responses and correlates with disease subtype and treatment exposure. Methods: We analyzed data from 332 patients with a hematologic malignancy from May 1, 2021 – Jan 31, 2022 who received SARS-CoV-2 vaccination and performed a prospective cohort serologic study with the Elecsys® Anti-SARS-CoV-2-S test. Patients received homologous or heterologous vaccine combination of BNT162b2, mRNA1273, ChAdOx1 nCoV-19, and/or Ad26.COV2.S. Blood samples were obtained before any vaccination, 2-6 weeks after the second vaccine (2V), before third vaccine (3V), and 2-6 weeks after 3V. Results: The median age was 67 years (range 18-91years) with 41.9% female. At 2V, 11.5% and at 3V, 23.8% received heterologous vaccines. Treatment status at first vaccine dose significantly affected peak 2V antibody response (p < 0.05). Seropositive rate and median antibody titer after 2V for previously untreated patients were higher compared to patients on active therapy or had previously been treated. Treatment naïve (n = 60; seropositivity 85.1%; median titer 1306 U/mL; [Q1-Q3:11.4- > 2499]); first-line (1L) active therapy (n = 127;65.4%; 41.25 U/mL; [ < 0.8-592.5]); second-line and beyond (2L+) active therapy (n = 56; 60.7%; 2.6U/mL; [ < 0.8-154]); previous treatment with 1L (n = 66;64.8%; 118 U/mL; [ < 0.8- > 2499]); previous treatment with 2L+ (n = 23; 59.1%; 4U/mL; [ < 0.8-229.5]). Of 61 patients that were seronegative at 2V, 17 (27.9%) seroconverted after 3V. Anti-CD20 monoclonal antibody (mAb) containing therapy as the most recent treatment from 2V had the greatest impact on humoral response. Exposure to anti-CD20 mAb based regimens or as monotherapy revealed low antibody responses (n = 84; seropositivity 22.6%; median titer < 0.8 U/mL; Q1-Q3 [ < 0.8- < 0.8]). On analysis of indolent B-cell Non-Hodgkin Lymphomas whereby antiCD-20 mAb are often incorporated, treatment proximity to 2V impacted responses: < 3 months (n = 33; 22%; < 0.8 U/mL; [ < 0.8- < 0.8]) vs. 12-24 months (n = 4; 60%; 228 U/mL; [ < 0.8-232]). In contrast, tyrosine kinase inhibitor (n = 38; 100%; 858 U/mL; [221- > 2499]), proteosome inhibitor monotherapy (n = 4;100%; median titer 1520 U/mL; [462- > 2499]) were among the subgroups with the highest numerical responses, however, the addition of corticosteroids impacted vaccine response as seen in proteosome inhibitor with corticosteroids (n = 7; 85.7%; 6.6 U/mL; [1.8-115.2]). Conclusions: The humoral response from our single institution cohort identifies diminished responses depending on treatment status and the type of treatment including the proximity of treatment exposure to receipt of vaccination. Furthermore, vaccine boosters can induce antibody responses in patients who were previously seronegative.

Fremanezumab (AJOVY; Teva Pharmaceutical Industries Ltd, Netanya, Israel), approved for the preventive treatment of migraine, is available as a subcutaneous injection either once a month or once every 3 months using an autoinjector or a prefilled syringe. The present study evaluated the pharmacokinetic (PK) bioequivalence of a single subcutaneous injection of fremanezumab 225 mg administered using an autoinjector compared to a prefilled syringe in healthy volunteers. Blood samples for PK and antidrug antibodies were collected before and after dosing. Safety and tolerability assessments included physical examinations, adverse event reporting, laboratory evaluations, and immunogenicity. Following single‐dose administration, the mean concentration‐time profiles for the 2 treatment groups (autoinjector, n = 106; and prefilled syringe, n = 110) were similar. The point estimates for the back‐transformed ratio (autoinjector/prefilled syringe) of geometric least squares means of maximum plasma concentration, area under the plasma concentration–time curve from time 0 to the time of the last measurable drug concentration, and area under the plasma concentration–time curve from time 0 extrapolated to infinity were 1.03, 1.04, and 1.05, respectively, with the 90% confidence intervals entirely contained within bioequivalence margins of 0.8 to 1.25. For both groups, median time to maximum observed concentration was 5 days and mean terminal elimination half‐life was approximately 29 days. Treatment‐related adverse events were reported by 39 (36%) subjects in the autoinjector group and 26 (24%) in the prefilled syringe group, and the majority were nonserious injection site reactions. The incidence of treatment‐emergent antidrug antibody response was low and evenly distributed between the autoinjector (n = 3; 3%) and prefilled syringe (n = 4; 4%) groups. These results indicate that the fremanezumab autoinjector presentation provides an easy‐to‐use bioequivalent PK profile with a similar safety and tolerability profile to that of the prefilled syringe.

Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient DNA replication and transcription. TOP1 is also a major driver of endogenous genome instability, particularly when its catalytic intermediate—a covalent TOP1-DNA adduct known as a TOP1 cleavage complex (TOP1cc)—is stabilised. TOP1ccs are highly cytotoxic and a failure to resolve them underlies the pathology of neurological disorders but is also exploited in cancer therapy where TOP1ccs are the target of widely used frontline anti-cancer drugs. A critical enzyme for TOP1cc resolution is the tyrosyl-DNA phosphodiesterase (TDP1), which hydrolyses the bond that links a tyrosine in the active site of TOP1 to a 3’ phosphate group on a single-stranded (ss)DNA break. However, TDP1 can only process small peptide fragments from ssDNA ends, raising the question of how the ~90 kDa TOP1 protein is processed upstream of TDP1. Here we find that TEX264 fulfils this role by forming a complex with the p97 ATPase and the SPRTN metalloprotease. We show that TEX264 recognises both unmodified and SUMO1-modifed TOP1 and initiates TOP1cc repair by recruiting p97 and SPRTN. TEX264 localises to the nuclear periphery, associates with DNA replication forks, and counteracts TOP1ccs during DNA replication. Altogether, our study elucidates the existence of a specialised repair complex required for upstream proteolysis of TOP1ccs and their subsequent resolution., Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient DNA replication and transcription. Here, the authors reveal insights into the molecular resolution of topoisomerase 1-DNA adducts by TEX264, p97 and SPRTN.

Malignant salivary gland tumors are rare neoplasms that are vastly heterogenous in their histological patterns and clinical behaviors. As a consequence, studies have lacked the robust sample sizes needed to define treatment strategies. In this study, we used the National Cancer Database to identify the incidence of occult nodal metastasis and effect on overall survival for the most common malignant salivary gland subtypes. A retrospective review of patients in the National Cancer Database with primary site malignancies of major salivary glands between 2004 and 2016 was performed. Subjects included in the study underwent surgical treatment with and without adjuvant radiation and had complete information on TNM pathological stage.8,689 patients with primary malignant salivary gland cancer were analyzed. The sample was stratified by histologic subtype. Univariate analysis of lymph node metastasis of the whole cohort showed a higher risk of death (p 0.001), when compared to those without. Also when comparing occult vs evident metastasis, the risk of death was higher for the latter (p 0.001).Occult cervical lymph node metastasis ranged from 14.9% to 35.8% in malignant salivary gland cancers, depending on histological subtype. Occult nodal metastasis was a poor prognostic factor with significantly worse overall survival.

To evaluate the relationship between intraoperative ischemia time with acute microvascular free tissue transfer (MFTT) complications in head and neck reconstruction.A systematic review using PRISMA guidelines was performed. Inclusion encompassed all available studies published and indexed using PubMed, Medline, and Embase. Meta-analyses were performed using the Cochrane Review Manager tool. Methodological Index for Non-Randomized Studies (MINORS), the Revised Cochrane risk-of-bias tool for randomized trials, and the NIH Study Quality Assessment Tool for non-randomized prospective studies.A total of 430 citations were reviewed. 25 were included in our overall qualitative analysis, and 14 for meta-analysis. When comparing ischemia times for flaps with and without complications, no significant difference was observed (p = 0.98). Additionally, in a separate cohort, no significant effect was realized when correlating ischemia time to overall rates and total complications.Ischemia time was not significantly different between those with and without acute flap complications.

To investigate the incidence of synchronous malignancies identified during triple endoscopy in patients with head and neck squamous cell carcinoma.A retrospective chart review of patients from a tertiary academic medical center was performed. Patients with a primary head and neck squamous cell carcinoma who underwent triple endoscopy were included. Operative, radiographic, and pathology reports were reviewed to evaluate for the presence of synchronous malignancies in the aerodigestive tract diagnosed through endoscopy. Demographics, relevant medical history, including tobacco and alcohol use, and tumor characteristics were recorded. Univariate and multivariate regression analyses were conducted to assess for associations with synchronous malignancy on triple endoscopy.215 patients were reviewed, 164 of which had a biopsy-positive head and neck squamous cell carcinoma and underwent triple endoscopy. Synchronous lesions were found in 8 patients (4.9%). Of the synchronous lesions, only two were identified on esophagoscopy and bronchoscopy; the remaining six were found on direct laryngoscopy. Clinical comorbidities including smoking and alcohol history, tumor p16 status, and tumor stage were not associated with presence of synchronous lesions. A positive synchronous lesion on positron emission tomography was significantly correlated with finding a synchronous lesion on triple endoscopy (p = 0.006).This study shows the incidence of synchronous lesions on triple endoscopy to be closer to 5%. While endoscopic examination can be useful in the anatomic characterization of head and neck malignancies, the low incidence of synchronous malignancies suggests that the need for triple endoscopy may be considered on a case-by-case basis.

Background Posterior retroperitoneoscopic adrenalectomy has gained widespread acceptance for the removal of benign adrenal tumors. Higher insufflation pressures using carbon dioxide (CO2) are required, although the ideal starting pressure is unclear. This prospective, randomized, single-blinded, study aims to compare physiologic differences with 2 different CO2 insufflation pressures during posterior retroperitoneoscopic adrenalectomy. Methods Participants were randomly assigned to a starting insufflation pressure of 20 mm Hg (low pressure) or 25 mm Hg (high pressure). The primary outcome measure was partial pressure of arterial CO2 at 60 minutes. Secondary outcomes included end-tidal CO2, arterial pH, blood pressure, and peak airway pressure. Breaches of protocol to change insufflation pressure were permitted if required and were recorded. Results A prospective randomized trial including 31 patients (low pressure: n = 16; high pressure: n = 15) was undertaken. At 60 minutes, the high pressure group had greater mean partial pressure of arterial CO2 (64 vs 50 mm Hg, P = .003) and end-tidal CO2 (54 vs 45 mm Hg, P = .008) and a lesser pH (7.21 vs 7.29, P = .0005). There were no significant differences in base excess, peak airway pressure, operative time, or duration of hospital stay. Clinically indicated protocol breaches were more common in the low pressure than the high pressure group (8 vs 3, P = .03). Conclusion In posterior retroperitoneoscopic adrenalectomy, greater insufflation pressures are associated with greater partial pressure of arterial CO2 and end-tidal CO2 and lesser pH at 60 minutes, be significant. Commencing with lesser CO2 insufflation pressures decreases intraoperative acidosis.

In head and neck squamous cell carcinoma (HNSCC), anti-PD-1 inhibitors are approved for recurrent/metastatic (R/M) disease and anticipated to expand to other indications. The impact of p16 status and anatomical site on overall survival (OS) in immunotherapy-treated HNSCC patients remains unresolved. We performed a retrospective analysis of R/M HNSCC patients receiving anti-PD-1 immunotherapy at our academic medical center with an extensive community satellite network. Fifty-three R/M HNSCC patients were treated with anti-PD-1 immunotherapy and had a median OS of 6 months. Anatomical site was associated with distinct OS, oropharynx and larynx patients have superior OS compared to oral cavity patients. Analysis of the OPSCC subset showed p16+ status as a favorable, independent prognostic biomarker (HR 7.67 (1.23–47.8), p = 0.029). Further studies to assess the link between anatomical site, p16 status, and anti-PD-1 treatment outcomes in large cohorts of R/M HNSCC patients managed in real-world clinical practices and clinical trials should be prioritized.

Objective To assess the impact of a microvascular head and neck (H&N) fellowship on senior residents' surgical experience. Study Design Retrospective review of Accreditation Council for Graduate Medical Education-generated operative case log reports, retrospective chart review, and electronic survey. Methods A retrospective review of one institution's residents' H&N operative case logs and free flap operative reports was performed to determine changes in key indicator cases (KICs) after the addition of a H&N fellowship. An electronic survey was distributed to senior residents at all U.S. otolaryngology residency programs to determine residents' perceptions of a H&N fellow's impact on their surgical experience. An electronic survey was distributed to senior medical students applying to surgical residencies to explore the perceived impact that a fellowship has on the desirability of a residency program. Results The average number of each postgraduate year (PGY)5's HN neck dissection, 33.2 versus 40.6; oral cavity resection, 15.3 versus 12.6; thyroid/parathyroid, 45.5 versus 45.6; and flaps/grafts, 56.7 versus 42. PGY5 participation as first assistant in free flaps dropped from 78% to 17%; however, residents still participated in some aspect of 45% of the cases. Seventy percent of senior residents reported a positive perception of the H&N fellow on their H&N operative experience. Eighty-nine percent of senior medical student respondents reported a nonnegative perception of a fellowship in their applied field. Conclusion The addition of a H&N fellowship did not decrease senior residents' H&N KIC, and most senior residents at programs with fellowships report that the fellow has a positive impact on their H&N operative experience. Level of Evidence 4. Laryngoscope, 2017

SummaryThe ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA2DS2-VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59–0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54–0.65) than warfarin initiators. Different types of stroke/SE and major bleeding – including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding – were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA2DS2-VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest “real-world” study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard-and low-dose apixaban dose regimens.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

Zinc-nickel single flow batteries (ZNBs) have been demonstrated as a promising alternative to lithium batteries for next generation grid-tied energy storage. However, due to the dendritic growth, the monitoring of working conditions in terms of the state of charge (SoC) and battery capacity is intractable. Although longer lifespan can be achieved through the periodic reconditioning maintenance, there is no mature method to identify the moment of reconditioning. Model predictive control (MPC) is a popular optimization paradigm in the process control. By incorporating the merits of model predictive control, this work presents a novel model predictive control based observer (MPCO) for the working conditions monitoring and reconditioning identification. Strong evidence from substantial experiments and simulations manifests the convergence, robustness, effectiveness and generality of the proposed method. The competitiveness is demonstrated by analytical comparisons against other three estimators. In this regard, the relationships of the proposed observer with other estimators are summarized briefly. At last, an indicator based on the capacity changes is proposed to judge the timing of reconditioning.

Background Patients may require microvascular free tissue transfer (MFTT) following re-irradiation for recurrent cancer or radiation complications. The objective of this study was to describe the indications for and outcomes of free flaps performed in twice-radiated patients. Methods A retrospective chart review identified the indications for and outcomes of 36 free flaps performed on 29 twice-irradiated patients. Results The free flap success rate was 92%. The most common indications requiring MFTT were cancer recurrence and osteoradionecrosis. Sixty-one percent experienced postoperative complications, most commonly wound infection (33%). Twenty-five percent of the procedures required return to the operating room due to postoperative complication. Conclusions MFTT can be successfully performed in the twice-irradiated patient population with a success rate comparable to singly-radiated patients. Despite a high success rate, there is also a high rate of surgical site complications, especially infection.

Histiocytic disorders can be classified according to the distribution pattern of the lesions and the organs involved. Non-Langerhans-cell histiocytosis is a rare group of diseases that have varied clinical presentations ranging from isolated masses to diffuse systemic eruptions. We discuss a patient who initially presented with a vocal cord lesion and was ultimately diagnosed with adult onset xanthogranuloma.

The reliable state of charge (SOC) estimation is indispensable for flow batteries to maintain the safe and reliable operation. The widely adopted Extended Kalman filter (EKF) algorithm is a model-based method, however, the uncertainties in battery model will cause large errors in SOC estimation. An accurate battery model is the essence to capture the behaviors of batteries. In this paper, a novel framework for the SOC estimation of Zinc-nickel flow batteries is proposed based on the fast recursive algorithm (FRA) and extended Kalman filter (EKF). The FRA is firstly used to determine the model structure and identify the model parameters. Due to merits of FRA, a compact and accurate model of flow battery is built. Then, the SOC is estimated using the EKF based on the proposed linear-in-the-parameter model. Experimental studies and resultant simulations manifest the modelling accuracy of the proposed SOC estimation framework.

Objectives To provide an understanding of darbepoetin alfa dose patterns in cancer patients undergoing myelosuppressive chemotherapy starting from 2011. Study design This is a retrospective cohort study using a proprietary outpatient oncology database. Methods Metastatic, solid tumor cancer patients receiving concomitant myelosuppressive chemotherapy and darbepoetin alfa with an associated hemoglobin Results Among 835 eligible patients, over 90% were 50 years or older. Mean chemotherapy course duration was 248 days, and mean duration of darbepoetin alfa treatment was 106 days. The mean weekly darbepoetin alfa dose was 110 µg. Patients received a mean of 4.3 darbepoetin alfa injections in the first chemotherapy course. There were no statistically significant differences (all P values > .05) in weekly dose by chemotherapy type, baseline hemoglobin level, year of chemotherapy, or solid tumor type. Conclusion The average weekly darbepoetin alfa dose among metastatic cancer patients with chemotherapy-induced anemia from this study was 110 µg, which was lower than the labeled dosage for most adults. This estimate did not differ over time, across chemotherapy regimens, baseline hemoglobin levels, or solid tumor types.

To assess the impact of a microvascular head and neck (HN) fellowship on senior residents' surgical experience.Retrospective review of Accreditation Council for Graduate Medical Education-generated operative case log reports, retrospective chart review, and electronic survey.A retrospective review of one institution's residents' HN operative case logs and free flap operative reports was performed to determine changes in key indicator cases (KICs) after the addition of a HN fellowship. An electronic survey was distributed to senior residents at all U.S. otolaryngology residency programs to determine residents' perceptions of a HN fellow's impact on their surgical experience. An electronic survey was distributed to senior medical students applying to surgical residencies to explore the perceived impact that a fellowship has on the desirability of a residency program.The average number of each postgraduate year (PGY)5's HN KIC before and after the addition of the fellowship were: parotidectomy, 19 versus 17.8; neck dissection, 33.2 versus 40.6; oral cavity resection, 15.3 versus 12.6; thyroid/parathyroid, 45.5 versus 45.6; and flaps/grafts, 56.7 versus 42. PGY5 participation as first assistant in free flaps dropped from 78% to 17%; however, residents still participated in some aspect of 45% of the cases. Seventy percent of senior residents reported a positive perception of the HN fellow on their HN operative experience. Eighty-nine percent of senior medical student respondents reported a nonnegative perception of a fellowship in their applied field.The addition of a HN fellowship did not decrease senior residents' HN KIC, and most senior residents at programs with fellowships report that the fellow has a positive impact on their HN operative experience.4. Laryngoscope, 128:52-56, 2018.