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Purpose: We examined operative efficiency, rate of facial nerve paresis, and post-operative outcomes in patients undergoing retrograde (RGD) vs anterograde dissection (AGD) of the facial nerve controlling for tumor location., Methods: Single-institution, retrospective analysis of patients with benign parotid tumors undergoing superficial parotidectomy with facial nerve dissection over a six-year period. Operative and pathology reports were reviewed to classify tumor size, location in relation to facial nerve branches, and technique for facial nerve dissection. Chi-square and Student's t-test were used to compare operative time, rates of facial nerve paresis, and post-operative outcomes between groups., Results: Our cohort included 35 patients who underwent RGD and 70 who underwent AGD of the facial nerve. Pleomorphic adenoma was most common in both the RGD (n = 25, 71.4 %) and AGD (n = 69, 98.6 %) groups. Both groups were balanced for demographics, tumor size and location in relation to facial nerve branches. Operative times, rate of surgical drain use, and frequency of post-operative admission were significantly reduced in the RGD group. The rate of temporary facial nerve paresis was significantly reduced (n = 3, 8.6 % vs n = 30, 42.9 % in the RGD vs AGD groups, respectively, p < 0.001) and more frequently limited to single nerve distributions in the RGD group., Conclusion: RGD of the facial nerve during superficial parotidectomy for benign parotid tumors is associated with reduced operative times, post-operative admission rates, and rates of facial nerve paresis compared to AGD even when controlling for tumor location., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity., Methods: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS)., Results: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively., Conclusion: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

Purpose: In locally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC), (i) to investigate kinetics of human papillomavirus (HPV) circulating tumor DNA (ctDNA) and association with tumor progression after chemoradiation, and (ii) to compare the predictive value of ctDNA to imaging biomarkers of MRI and FDG-PET., Experimental Design: Serial blood samples were collected from patients with AJCC8 stage III OPSCC ( n = 34) enrolled on a randomized trial: pretreatment; during chemoradiation at weeks 2, 4, and 7; and posttreatment. All patients also had dynamic-contrast-enhanced and diffusion-weighted MRI, as well as FDG-PET scans pre-chemoradiation and week 2 during chemoradiation. ctDNA values were analyzed for prediction of freedom from progression (FFP), and correlations with aggressive tumor subvolumes with low blood volume (TV LBV ) and low apparent diffusion coefficient (TV LADC ), and metabolic tumor volume (MTV) using Cox proportional hazards model and Spearman rank correlation., Results: Low pretreatment ctDNA and an early increase in ctDNA at week 2 compared with baseline were significantly associated with superior FFP ( P < 0.02 and P < 0.05, respectively). At week 4 or 7, neither ctDNA counts nor clearance were significantly predictive of progression ( P = 0.8). Pretreatment ctDNA values were significantly correlated with nodal TV LBV , TV LADC , and MTV pre-chemoradiation ( P < 0.03), while the ctDNA values at week 2 were correlated with these imaging metrics in primary tumor. Multivariate analysis showed that ctDNA and the imaging metrics performed comparably to predict FFP., Conclusions: Early ctDNA kinetics during definitive chemoradiation may predict therapy response in stage III OPSCC., (©2021 American Association for Cancer Research.)

Despite the rising incidence of human papillomavirus related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), treatment of metastatic disease remains palliative. Even with new treatments such as immunotherapy, response rates are low and can be delayed, while even mild tumor progression in the face of an ineffective therapy can lead to rapid death. Real-time biomarkers of response to therapy could improve outcomes by guiding early change of therapy in the metastatic setting. Herein, we developed and analytically validated a new droplet digital PCR (ddPCR)-based assay for HPV16 circulating tumor DNA (ctDNA) and evaluated plasma HPV16 ctDNA for predicting treatment response in metastatic HPV+ OPSCC. We found that longitudinal changes HPV16 ctDNA correlate with treatment response and that ctDNA responses are observed earlier than conventional imaging (average 70 days, range: 35-166). With additional validation in multi-site studies, this assay may enable early identification of treatment failure, allowing patients to be directed promptly toward clinical trials or alternative therapies., Competing Interests: CONFLICTS OF INTEREST The study team has filed an invention disclosure on the HPV16 ctDNA assay and the University of Michigan intends to file a patent on the assay technology., (Copyright: © 2021 Haring et al.)

Aim: To describe a novel technique for the reconstruction of geometrically complex defects of the midface using an osteotomized folded scapular tip-free flap., Methods: Five patients underwent maxillectomy with defects disrupting two or more of the following facial axes: orbital, nasofacial, and palatal axes. Patients underwent primary reconstruction using an angular artery-based scapular tip-free flap with an osteotomy to fold the flap. Harvest techniques, including placement of osteotomies, folding and plating, surgical esthetic, and functional outcomes, are presented., Results: Osteotomies placed in the scapular tip-free flap allowed folding of the osseous flap and improved restoration of all three facial axes with a single flap. In one patient, the tip of the scapula was used to reconstruct the nasofacial axis, while the body and lateral border were used to reconstruct the palate. In four patients, the tip of the scapula was used to reconstruct the orbital axis, while the body and lateral border were used to reconstruct the nasofacial axis. Patients had successful oronasal separation, healed wounds withstanding adjuvant therapy, satisfactory orbital positioning and facial projection, preserved masticatory surfaces and opportunity for dental implants., Conclusion: The midface is geometrically complex and is one of the most challenging head and neck sites to reconstruct. Ablative defects in this area can disrupt facial axes resulting in poor esthetic and functional outcomes. This study demonstrates the reconstructive advantages of a novel osteotomized folded scapular tip-free flap., Competing Interests: Conflicts of interest All authors declared that there are no conflicts of interest.

Background: Current limitations in the supply of ventilators during the Covid19 pandemic have limited respiratory support for patients with respiratory failure. Split ventilation allows a single ventilator to be used for more than one patient but is not practicable due to requirements for matched patient settings, risks of cross-contamination, harmful interference between patients and the inability to individualize ventilator support parameters. We hypothesized that a system could be developed to circumvent these limitations., Methods and Findings: A novel delivery system was developed to allow individualized peak inspiratory pressure settings and PEEP using a pressure regulatory valve, developed de novo, and an inline PEEP 'booster'. One-way valves, filters, monitoring ports and wye splitters were assembled in-line to complete the system and achieve the design targets. This system was then tested to see if previously described limitations could be addressed. The system was investigated in mechanical and animal trials (ultimately with a pig and sheep concurrently ventilated from the same ventilator). The system demonstrated the ability to provide ventilation across clinically relevant scenarios including circuit occlusion, unmatched physiology, and a surgical procedure, while allowing significantly different pressures to be safely delivered to each animal for individualized support., Conclusions: In settings of limited ventilator availability, systems can be developed to allow increased delivery of ventilator support to patients. This enables more rapid deployment of ventilator capacity under constraints of time, space and financial cost. These systems can be smaller, lighter, more readily stored and more rapidly deployable than ventilators. However, optimizing ventilator support for patients with individualized ventilation parameters will still be dependent upon ease of use and the availability of medical personnel., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: KVK, GEG and DAZ are founders of MakeMedical LLC, which is the legal manufacturer of this device (provided at cost). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Children with bipolar disorder (BD) or severe mood dysregulation (SMD) show behavioural and neural deficits during facial emotion processing. In those with other psychiatric disorders, such deficits have been associated with reduced attention to eye regions while looking at faces., Methods: We examined gaze fixation patterns during a facial emotion labelling task among children with pediatric BD and SMD and among healthy controls. Participants viewed facial expressions with varying emotions (anger, fear, sadness, happiness, neutral) and emotional levels (60%, 80%, 100%) and labelled emotional expressions., Results: Our study included 22 children with BD, 28 with SMD and 22 controls. Across all facial emotions, children with BD and SMD made more labelling errors than controls. Compared with controls, children with BD spent less time looking at eyes and made fewer eye fixations across emotional expressions. Gaze patterns in children with SMD tended to fall between those of children with BD and controls, although they did not differ significantly from either of these groups on most measures. Decreased fixations to eyes correlated with lower labelling accuracy in children with BD, but not in those with SMD or in controls., Limitations: Most children with BD were medicated, which precluded our ability to evaluate medication effects on gaze patterns., Conclusion: Facial emotion labelling deficits in children with BD are associated with impaired attention to eyes. Future research should examine whether impaired attention to eyes is associated with neural dysfunction. Eye gaze deficits in children with BD during facial emotion labelling may also have treatment implications. Finally, children with SMD exhibited decreased attention to eyes to a lesser extent than those with BD, and these equivocal findings are worthy of further study.