Interim Phase II Results Using Panitumumab-IRDye800CW During Transoral Robotic Surgery in Patients with Oropharyngeal Cancer.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but have the greatest potential impact for improving patient care when the surgeon has limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in OPSCC patients. PATIENTS AND METHODS: 12 consecutive patients with OPSCC were enrolled as part of a non-randomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. RESULTS: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. CONCLUSIONS: Results from this OPSCC patient cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

Therapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b+ myeloid cells.

Cumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models. The frequency of regulatory T (Treg) cells in spinal cords from chronic EAE mice treated with IFN-γ was significantly increased with no effect on Th1 and Th17 cells. Consistently, depletion of FOXP3-expressing cells blocked the protective effects of IFN-γ, indicating that the therapeutic effect of IFN-γ depends on the presence of Treg cells. However, IFN-γ did not trigger direct in vitro differentiation of Treg cells. In vivo administration of blocking antibodies against either interleukin (IL)-10, transforming growth factor (TGF)-ß or program death (PD)-1, revealed that the protective effects of IFN-γ in EAE were also dependent on TGF-ß and PD-1, but not on IL-10, suggesting that IFN-γ might have an indirect role on Treg cells acting through antigen-presenting cells. Indeed, IFN-γ treatment increased the frequency of a subset of splenic CD11b+ myeloid cells expressing TGF-ß-Latency Associated Peptide (LAP) and program death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)-1-dependent manner. Furthermore, splenic CD11b+ cells from EAE mice preconditioned in vitro with IFN-γ and myelin oligodendrocyte glycoprotein (MOG) peptide exhibited a tolerogenic phenotype with the capability to induce conversion of naïve CD4+ T cells mediated by secretion of TGF-ß. Remarkably, adoptive transfer of splenic CD11b+ cells from IFN-γ-treated EAE mice into untreated recipient mice ameliorated clinical symptoms of EAE and limited central nervous system infiltration of mononuclear cells and effector helper T cells. These results reveal a novel cellular and molecular mechanism whereby IFN-γ promotes beneficial effects in EAE by endowing splenic CD11b+ myeloid cells with tolerogenic and therapeutic activities.

Repeat Radiosurgery for Sporadic Vestibular Schwannoma After Primary Radiosurgical Failure: An International Multi-institutional Investigation.

OBJECTIVE: To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. STUDY DESIGN: Multi-institutional historical cohort study. SETTING: Five tertiary care referral centers. PATIENTS: Adults ≥18 years old with sporadic VS. INTERVENTION: Primary and repeat treatment with SRS. MAIN OUTCOME MEASURE: Microsurgery-free survival after repeat SRS. RESULTS: Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. CONCLUSION: Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.

The Use of Text Messaging as an Adjunct to Internet-Based Cognitive Behavioral Therapy for Major Depressive Disorder in Youth: Secondary Analysis.

BACKGROUND: As an established treatment for major depressive disorder (MDD), cognitive behavioral therapy (CBT) is now implemented and assessed in internet-based formats that, when combined with smartphone apps, enable secure text messaging. As an adjunct to such internet-based CBT (ICBT) approaches, text messaging has been associated with increased adherence and therapeutic alliance. OBJECTIVE: This study analyzed data from the intervention arm of a randomized control trial evaluating 24-week ICBT for MDD (intervention arm) against standard-care psychiatry (waitlist control). The aim of this secondary analysis was to assess MDD symptom improvement in relation to the frequency and content of text messages sent by ICBT participants to Navigator-Coaches during randomized control trial participation. Higher text frequency in general and in 3 conceptual categories (appreciating alliance, alliance building disclosures, and agreement confirmation) was hypothesized to predict larger MDD symptom improvement. METHODS: Participants were young adults (18-30 years) from the Centre for Addiction and Mental Health. The frequencies of categorized texts from 20 ICBT completers were analyzed with respect to MDD symptom improvement using linear regression models. Texts were coded by 2 independent coders and categorized using content analysis. MDD symptoms were measured using the Beck Depression Inventory-II (BDI-II). RESULTS: Participants sent an average of 136 text messages. Analyses indicated that BDI-II improvement was negatively associated with text messaging frequency in general (ß=-0.029, 95% CI -0.11 to 0.048) and in each of the 3 categories: appreciating alliance (ß=-0.096, 95% CI -0.80 to 0.61), alliance building disclosures (ß=-0.098, 95% CI -0.28 to 0.084), and agreement confirmation (ß=-0.076, 95% CI -0.40 to 0.25). Altogether, the effect of text messaging on BDI-II improvement was uniformly negative across statistical models. More text messaging appeared associated with less MDD symptom improvement. CONCLUSIONS: The hypothesized positive associations between conceptually categorized text messages and MDD symptom improvement were not supported in this study. Instead, more text messaging appeared to indicate less treatment benefit. Future studies with larger samples are needed to discern the optimal use of text messaging in ICBT approaches using adjunctive modes of communication. TRIAL REGISTRATION: Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052.

Salvage Microsurgery Following Failed Primary Radiosurgery in Sporadic Vestibular Schwannoma.

Importance: Management of sporadic vestibular schwannoma with radiosurgery is becoming increasingly common globally; however, limited data currently characterize patient outcomes in the setting of microsurgical salvage for radiosurgical failure. Objective: To describe the clinical outcomes of salvage microsurgery following failed primary stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) among patients with sporadic vestibular schwannoma. Design, Setting, and Participants: This was a cohort study of adults (≥18 years old) with sporadic vestibular schwannoma who underwent salvage microsurgery following failed primary SRS/FSRT in 7 vestibular schwannoma treatment centers across the US and Norway. Data collection was performed between July 2022 and January 2023, with data analysis performed between January and July 2023. Exposure: Salvage microsurgical tumor resection. Main Outcomes and Measures: Composite outcome of undergoing less than gross total resection (GTR) or experiencing long-term facial paresis. Results: Among 126 patients, the median (IQR) age at time of salvage microsurgery was 62 (53-70) years, 69 (55%) were female, and 113 of 117 (97%) had tumors that extended into the cerebellopontine angle at time of salvage. Of 125 patients, 96 (76%) underwent primary gamma knife SRS, while 24 (19%) underwent linear accelerator-based SRS; the remaining patients underwent FSRT using other modalities. Postoperative cerebrospinal fluid leak was seen in 15 of 126 patients (12%), hydrocephalus in 8 (6%), symptomatic stroke in 7 (6%), and meningitis in 2 (2%). Each 1-mm increase in cerebellopontine angle tumor size was associated with a 13% increased likelihood of foregoing GTR (64 of 102 patients [63%]) or long-term postoperative House-Brackmann grade higher than I (48 of 102 patients [47%]) (odds ratio, 1.13; 95% CI, 1.04-1.23). Following salvage microsurgery, tumor growth-free survival rates at 1, 3, and 5 years were 97% (95% CI, 94%-100%), 93% (95% CI, 87%-99%), and 91% (95% CI, 84%-98%), respectively. Conclusions: In this cohort study, more than half of patients who received salvage microsurgery following primary SRS/FSRT underwent less than GTR or experienced some degree of facial paresis long term. These data suggest that the cumulative risk of developing facial paresis following primary SRS/FSRT by the end of the patient's journey with treatment approximates 2.5% to 7.5% when using published primary SRS/FSRT long-term tumor control rates.

Sporadic vestibular schwannoma in a pediatric population: a case series.

PURPOSE: To describe the characteristics, management, and outcomes of pediatric patients with sporadic vestibular schwannoma (sVS). METHODS: This was a case series at a tertiary care center. Patients were identified through a research repository and chart review. Interventions were microsurgery, stereotactic radiosurgery (SRS), and observation. Outcome measures were tumor control, facial nerve function, and hearing. RESULTS: Eight patients over 2006-2022 fulfilled inclusion criteria (unilateral VS without genetic or clinical evidence of neurofibromatosis type 2 (NF2); age ≤ 21) with a mean age of 17 years (14-20). Average greatest tumor length in the internal auditory canal was 9.7 mm (4.0-16.1). Average greatest tumor dimension (4/8 tumors) in the cerebellopontine angle was 19.1 mm (11.3-26.8). Primary treatment was microsurgery in five (62.5%) patients, observation in two (25%), and SRS in one (12.5%). Four (80%) surgical patients had gross total resections, and one (20%) had regrowth post-near total resection and underwent SRS. One observed patient and the primary SRS patient have remained radiographically stable for 3.5 and 7 years, respectively. The other observed patient required surgery for tumor growth after 12 months of observation. Two surgical patients had poor facial nerve outcomes. All post-procedural patients developed anacusis. Mean follow-up was 3 years (0.5-7). CONCLUSIONS: We describe one of the largest reported cohorts of pediatric sVS in the USA. Diligent exclusion of NF2 is critical. Given the high likelihood of eventually requiring intervention and known adverse effects of SRS, microsurgery remains the preferred treatment. However, observation can be considered in select situations.

The formality effect.

This paper documents the existence of a 'formality effect' in government communications. Across three online studies and three field experiments in different policy contexts (total N = 67,632), we show that, contrary to researcher and practitioner predictions, formal government communications are more effective at influencing resident behaviour than informal government communications. In exploring mechanisms, we show that formality operates as a heuristic for credibility and importance. Recipients view the source of a formal letter as more competent and trustworthy, and view the request itself as more important to take action on, despite no evidence of change in comprehension or in perceived ease of taking action. These findings have immediate implications for government communicators and open the door for a renewed focus on how the design and presentation of information impacts behaviour.

Mortui vivos docent: a modern revival of temporal bone plug harvests.

Human temporal bones (HTBs) are invaluable resources for the study of otologic disorders and for evaluating novel treatment approaches. Given the high costs and technical expertise required to collect and process HTBs, there has been a decline in the number of otopathology laboratories. Our objective is to encourage ongoing study of HTBs by outlining the necessary steps to establish a pipeline for collection and processing of HTBs. In this methods manuscript, we: (1) provide the design of a temporal bone plug sawblade that can be used to collect specimens from autopsy donors; (2) establish that decalcification time can be dramatically reduced from 9 to 3 months if ethylenediaminetetraacetic acid is combined with microwave tissue processing and periodic bone trimming; (3) show that serial sections of relatively-rapidly decalcified HTBs can be successfully immunostained for key inner ear proteins; (4) demonstrate how to drill down a HTB to the otic capsule within a few hours so that subsequent decalcification time can be further reduced to only weeks. We include photographs and videos to facilitate rapid dissemination of the developed methods. Collected HTBs can be used for many purposes, including, but not limited to device testing, imaging studies, education, histopathology, and molecular studies. As new technology develops, it is imperative to continue studying HTBs to further our understanding of the cellular and molecular underpinnings of otologic disorders.

Promoting Surgeon-Scientists in Otolaryngology-Head and Neck Surgery-From Bench to Bedside.

Importance: Surgeon-scientists (defined as principal investigators [PIs] with a Doctor of Medicine [MD] degree or a combined MD and Doctor of Philosophy [PhD] degree) in otolaryngology-head and neck surgery (OHNS) are imperative for achieving clinical translation in the OHNS field. Objective: To (1) raise awareness about the current state of surgeon-scientists in OHNS, (2) contextualize the landscape of surgeon-scientists in OHNS by comparing it to those of neurosurgery and ophthalmology, and (3) identify strategies for attracting and retaining surgeon-scientists in OHNS. Evidence Review: Research funding data from fiscal years 2015 to 2021 among surgeon-scientists in OHNS, neurosurgery, and ophthalmology were obtained from the National Institutes of Health (NIH) Research Portfolio Online Reporting Tools Expenditures and Results and the US Department of Defense (DOD) Congressionally Directed Medical Research Programs awards database. The Association of American Medical Colleges provided the total number of active physicians in each specialty per year and the number and percentage of residents with an MD-PhD degree in each specialty per year. Cohen d was used to express the standardized value of the magnitude of the mean difference between compared groups. Findings: From 2015 to 2021, on average, there were 9566 active physicians in OHNS, 5559.8 in neurosurgery, and 18908.8 in ophthalmology. In OHNS, a greater number of NIH K (research career development) grants were held by surgeon-scientists than by PIs with a PhD degree (21.4 vs 5.1; mean difference, 16.3; 95% CI, 14.3-18.3; Cohen d = 9.6), whereas most NIH R (research) and U (cooperative agreement) grants (144.1 vs 81.6; mean difference, 62.6; 95% CI, 46.3-78.9; Cohen d = 4.5) and DOD grants (9.9 vs 4.1; mean difference, 5.7; 95% CI, 1.0-10.4; Cohen d = 1.4) were held by PIs with a PhD degree. In a comparison of OHNS to neurosurgery and ophthalmology, after the number of R and U grants was scaled by the number of physicians in each field, neurosurgery had a much greater number of grants per surgeon than OHNS (0.02 vs 0.01; mean difference, 0.01; 95% CI, 0.01-0.02; Cohen d = 4.2). Additionally, neurosurgeons received a much larger R and U grant amount per physician than otolaryngologists ($10 630.20 vs $4511.80; mean difference, $6118.40; 95% CI, $2625.90-$9610.80; Cohen d = 2.0). For the R and U grant metrics, there were no meaningful differences between OHNS and ophthalmology. Conclusions and Relevance: Results of this database study showed that from 2015 to 2021, the number of governmental grants held by surgeon-scientists in OHNS increased, but there is room for improvement given the metrics of neurosurgeons, a population smaller than otolaryngologists. Possible strategies include intramural research grants, surgeon-scientist training programs, and partnerships between specialty societies and NIH administering institutes and centers.

The Future of Vestibular Schwannoma Management.

The future of the management of both sporadic and neurofibromatosis type 2-asscoiated vestibular schwannomas (VSs) will be shaped by cutting-edge technologic and biomedical advances to enable personalized, precision medicine. This scoping review envisions the future by highlighting the most promising developments published, ongoing, planned, or potential that are relevant for VS, including integrated omics approaches, artificial intelligence algorithms, biomarkers, liquid biopsy of the inner ear, digital medicine, inner ear endomicroscopy, targeted molecular imaging, patient-specific stem cell-derived models, ultra-high dose rate radiotherapy, optical imaging-guided microsurgery, high-throughput development of targeted therapeutics, novel immunotherapeutic strategies, tumor vaccines, and gene therapy.

Perspectives From Extension Staff on Building and Sustaining Community Wellness Coalitions.

BACKGROUND: Community wellness coalitions are an important part of functioning program infrastructure and have been effective in promoting policy, systems, and environmental (PSE) change, especially when paired with technical support by a community champion or Extension staff. PSE strategies are critical to support long-lasting behavior change but can be challenging to implement. Extension is an established and equipped organization that has potential to help community overcome those challenges. The aim of this article was to identify and describe experiences of Extension staff working as community coaches. METHODS: A mixed-methods design to assess the impact of Extension staff working with Community Champions included a quantitative Extension Coaching Confidence Scorecard and an Extension Key Informant Interview. RESULTS: The total Extension Coaching Confidence score significantly increased from pre- to post-intervention (55.1 ± 35.3 vs. 81.7 ± 37.7, p = .03). Five facilitators and two barriers to wellness coalition development were identified by Extension staff. DISCUSSION: The results of this study indicate that the model of community coaching used was effective at addressing the foundational components of the Component Model of Infrastructure (CMI). However, comprehensive training for Extension staff in the CMI and technical assistance are needed in order to build capacity, achieve outcomes, and promote sustainability. IMPLICATIONS FOR PRACTICE: Individuals seeking to transition to PSE work should be provided with a foundation of specific, targeted training in the CMI and evidence-based technical assistance methods. Practitioners should recognize the essential role of community champions in PSE work. Completing the Extension Coaching Confidence Scorecard periodically can inform evolving training needs.

Facilitating Nutrition and Physical Activity-Focused Policy, Systems, and Environmental Change in Rural Areas: A Methodological Approach Using Community Wellness Coalitions and Cooperative Extension.

Obesity prevalence is higher among rural populations than urban, which may be related to differences in environments. Rural counties face barriers to accessing healthy foods and physical activity opportunities including isolation, transportation distances, and lack of facilities. As part of the Centers for Disease Control and Prevention Division of Nutrition, Physical Activity, and Obesity High Obesity Program, community-based wellness coalitions were established in six South Dakota counties with adult obesity prevalence >40%. The community coalitions were charged with improving access to healthy foods and safe and accessible places to participate in physical activity within their rural, underserved communities. Coalitions were created and members were recruited by Cooperative Extension staff who had existing relationships with key stakeholders within the community. Within these coalitions, champions were identified to provide leadership and ensure project implementation. Ongoing support and technical assistance were provided to the community coalitions by Cooperative Extension staff as they completed a community needs assessment, disseminated results of the needs assessment with the community, created action plans based on needs assessment data, implemented evidence-based interventions to support nutrition and physical activity policy, system and environmental changes, and assessed impact within their community. Overall, the purpose of this article is to share the project methodology, which capitalized on using Cooperative Extension, to build capacity to improve the nutrition and physical activity environment in rural, unserved communities. Sustainability of this work, along with lessons learned, is also discussed.

Engineered red blood cells (activating antigen carriers) drive potent T cell responses and tumor regression in mice.

Activation of T cell responses is essential for effective tumor clearance; however, inducing targeted, potent antigen presentation to stimulate T cell responses remains challenging. We generated Activating Antigen Carriers (AACs) by engineering red blood cells (RBCs) to encapsulate relevant tumor antigens and the adjuvant polyinosinic-polycytidylic acid (poly I:C), for use as a tumor-specific cancer vaccine. The processing method and conditions used to create the AACs promote phosphatidylserine exposure on RBCs and thus harness the natural process of aged RBC clearance to enable targeting of the AACs to endogenous professional antigen presenting cells (APCs) without the use of chemicals or viral vectors. AAC uptake, antigen processing, and presentation by APCs drive antigen-specific activation of T cells, both in mouse in vivo and human in vitro systems, promoting polyfunctionality of CD8+ T cells and, in a tumor model, driving high levels of antigen-specific CD8+ T cell infiltration and tumor killing. The efficacy of AAC therapy was further enhanced by combination with the chemotherapeutic agent Cisplatin. In summary, these findings support AACs as a potential vector-free immunotherapy strategy to enable potent antigen presentation and T cell stimulation by endogenous APCs with broad therapeutic potential.

Above and Beyond: Periorbital Suspension for Endoscopic Access to Difficult Frontal Sinus Pathology.

OBJECTIVES/HYPOTHESIS: The periorbital suspension (PS) is an advanced adjunctive technique performed during endoscopic approaches to frontal sinus pathology that would be too far lateral or superior to address using traditional endoscopic transnasal approaches. The objectives of this study are to characterize the utility of this technique for frontal sinus pathology, determine anatomic limitations, and assess clinical outcomes following surgical treatment. STUDY DESIGN: Prospective case series. METHODS: Patient data including demographics, etiology, technique, complications, and clinical follow-up were collected. Preoperative computed tomography scans were reviewed for maximum lateral and superior extent of pathology, supraorbital recess height, anterio-posterior (AP) diameter of the frontal sinus, interorbital distance, and orbital-first olfactory neuron distance. RESULTS: The PS approach was used in 30 surgeries (29 patients) for cerebrospinal fluid leaks (n = 5), benign tumors (n = 17), malignant tumors (n = 5), allergic fungal sinusitis (n = 2), and mucocele (n = 1) between 2018 and 2020. Approaches included 15 Draf IIB and 15 Draf III frontal sinusotomies. All pathology was surgically accessible using the PS approach and there were no intraoperative or postoperative complications. Postoperative follow-up was 11.7 ± 7.6 months. Mean recorded measurements (in mm) were as follows: maximum lateral extent -15.0 ± 7.7, superior extent 21.2 ± 7.7 in surgical plane and 20.9 ± 9.8 in the vertical plane, supraorbital recess height -2.6 ± 1.9, AP frontal sinus diameter -13.2 ± 4.7, interorbital distance -29.8 ± 5.4, and orbital-olfactory neuron distance -14.8 ± 2.9. CONCLUSIONS: The PS technique can be safely and successfully utilized to provide endoscopic endonasal access to lateral and superior frontal sinus pathology. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:538-544, 2022.

Moving to a more restrictive transfusion protocol: Outcomes in head and neck free flap surgery.

PURPOSE: To determine if a more restrictive transfusion protocol results in increased rates of adverse flap outcomes in patients undergoing free tissue transfer. MATERIALS AND METHODS: Mixed retrospective and prospective cohort study. Patients who underwent surgery before the protocol change were collected retrospectively. Patients who underwent surgery after the protocol change were collected prospectively. RESULTS: Of the 460 patients who underwent free tissue transfer, 116 patients in the pre-change cohort (N = 211) underwent transfusion (54.98%) and 78 in the post-change cohort(N = 249) (31.33%) (p < 0.001). The mean number of units transfused was 1.55 + 2.00 in the pre-change cohort, and 0.78 + 1.51 in the post-change cohort (p < 0.001). When separated temporally, the pre-change cohort received significantly more blood transfusions than the post-change cohort in the operating room (33.65% vs 18.07%) (p < 0.01), within 72 h of surgery (35.55% vs 15.66%) (p < 0.001), and after 72 h after surgery to discharge (16.59% vs 8.03%) (p = 0.018017). The rate of flap failure was 6.70% in the pre-change cohort, and 5.31% in the post-change cohort (p = 0.67). In a logistic regression model controlling for potential confounders, transfusion protocol was not significantly associated with flap failure (OR = 1.1080, 95% CI: 0.48-2.54). There were no significant differences between cohorts for medical morbidity, ICU transfer, or death. CONCLUSION: Our data support the conclusion that patients undergoing free tissue transfer to the head and neck can be transfused following the same protocols as other patients, without increasing the rate of flap failure or other morbidities. LEVEL OF EVIDENCE: 3 (mixed retrospective, prospective cohort study).

Quantifying the Food and Physical Activity Environments in Rural, High Obesity Communities.

The built environment contributes to an individual's health, and rural geographies face unique challenges for healthy eating and active living. The purpose of this descriptive study was to assess the nutrition and physical activity environments in rural communities with high obesity prevalence. One community within each of six high obesity prevalence counties in a rural Midwest state completed the Nutrition Environment Measures Survey for Stores (NEMS-S) and the Rural Active Living Assessment (RALA). Data were collected by trained community members and study staff. All communities had at least one grocery store and five had at least one convenience store. Grocery stores had higher mean total NEMS-S scores than convenience stores (26.6 vs. 6.0, p < 0.001), and higher scores for availability (18.7 vs. 5.3, p < 0.001) and quality (5.4 vs. 0, p < 0.001) of healthful foods (higher scores are preferable). The mean RALA town-wide assessment score across communities was 56.5 + 15.6 out of a possible 100 points. The mean RALA program and policy assessment score was 40.8 + 20.4 out of a possible 100 points. While grocery stores and schools are important for enhancing food and physical environments in rural areas, many opportunities exist for improvements to impact behaviors and address obesity.

Review of referrals reveal the impact of referral content on the triage and management of ophthalmology wait lists.

OBJECTIVES: Many chronic eye conditions are managed within public hospital ophthalmology clinics resulting in encumbered wait lists. Integrated care schemes can increase system capacity. In order to direct implementation of a public hospital-based integrated eye care model, this study aims to evaluate the quality of referrals for new patients through information content, assess triage decisions of newly referred patients and evaluate the consistency of referral content for new patients referred multiple times. DESIGN: A retrospective and prospective review of all referral forms for new patients referred to a public hospital ophthalmology clinic between January 2016 and September 2017, and September 2017 and August 2018, respectively. SETTING: A referral-only public hospital ophthalmology clinic in metropolitan Sydney, Australia. PARTICIPANTS: 418 new patients on existing non-urgent wait lists waiting to be allocated an initial appointment, and 528 patients who were newly referred. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the information content of referrals for new patients. The secondary outcomes were triage outcomes for new incoming referrals, and the number of new patients with multiple referrals. RESULTS: Of the wait-listed referrals, 0.2% were complete in referral content compared with 9.8% of new incoming referrals (p<0.001). Of new incoming referrals, 56.7% were triaged to a non-urgent clinic. Multiple referrals were received for 49 patients, with no change in the amount of referral content. CONCLUSIONS: Most referrals were incomplete in content, leading to triage based on limited clinical information. Some new patients were referred multiple times with their second referral containing a similar amount of content as their first. Lengthy wait lists could be prevented by improving administrative processes and communication between the referral centre and referrers. The future implementation of an integrated eye care model at the study setting could sustainably cut wait lists for patients with chronic eye conditions.

Predicting Schwannoma Growth in a Tumor Model Using Targeted Imaging.

INTRODUCTION: Vestibular schwannoma (VS) is a common pathology encountered in neurotology clinics. Many patients are observed with a "wait and scan" approach. Previous efforts to determine radiographic indicators of future growth have been unsuccessful. Using a mouse subcutaneous tumor model, we seek to determine if fluorescent imaging with directed immunotargets could be used to predict schwannoma growth rate. METHODS: Anti-VEGFR2 and anti-Her2/Neu monoclonal antibodies were covalently linked to a near-infrared probe (IRDye800). Immunodeficient mice underwent subcutaneous injections with a rat-derived schwann (R3) cell line. When tumor growth was evident, either Anti-VEGFR2-IRDye800, anti-Her2/Neu-IRDye800, or Immunoglobulin G (IgG) Isotype-IRDye800 (control) were injected via tail vein. The mice were serially imaged in a closed field near-IR device. Fluorescent data were analyzed for tumor signal and correlated with tumor sie and growth rate. Heterogeneity of fluorescent tumor signal was also assessed. RESULTS: In both anti-VEGFR2 and anti-Her2/Neu groups, there were strong correlations between day 1 mean tumor fluorescence and eventual maximum tumor volume (p = 0.002, 0.001; r2 = 0.92, 0.86). There was also strong correlation with maximum tumor signal on day 1 and maximum tumor volume (p = 0.003, 0.008; r2 = 0.90, 0.91). There was no such correlation in the control group (p = 0.99, 0.75; r2 = 0.0002, 0.028). CONCLUSION: Given the potential morbidity in VS intervention, observation is an appropriate approach for patients with slow-growing or stagnant tumors. We seek to identify immunotargets in a murine model that show promise in predicting schwannoma growth with advanced imaging techniques. Both Her2/Neu and VEGFR2 correlated strongly wth tumor size and growth rates and are promising targets that merit further investigation.

Comparison of Panitumumab-IRDye800CW and 5-Aminolevulinic Acid to Provide Optical Contrast in a Model of Glioblastoma Multiforme.

Maximal safe resection of malignant tissue is associated with improved progression-free survival and better response to radiation and chemotherapy for patients with glioblastoma (GBM). 5-Aminolevulinic acid (5-ALA) is the current FDA-approved standard for intraoperative brain tumor visualization. Unfortunately, autofluorescence in diffuse areas and high fluorescence in dense tissues significantly limit discrimination at tumor margins. This study is the first to compare 5-ALA to an investigational new drug, panitumumab-IRDye800CW, in the same animal model. A patient-derived GBM xenograft model was established in 16 nude mice, which later received injections of 5-ALA, panitumumab-IRDye800CW, IRDye800CW, 5-ALA and IRDye800CW, or 5-ALA and panitumumab-IRDye800CW. Brains were prepared for multi-instrument fluorescence imaging, IHC, and quantitative analysis of tumor-to-background ratio (TBR) and tumor margin accuracy. Statistical analysis was compared with Wilcoxon rank-sum or paired t test. Panitumumab-IRDye800CW had a 30% higher comprehensive TBR compared with 5-ALA (P = 0.0079). SDs for core and margin regions of interest in 5-ALA-treated tissues were significantly higher than those found in panitumumab-IRDye800CW-treated tissues (P = 0.0240 and P = 0.0284, respectively). Panitumumab-IRDye800CW specificities for tumor core and margin were more than 10% higher than those of 5-ALA. Higher AUC for panitumumab-IRDye800CW indicated strong capability to discriminate between normal and malignant brain tissue when compared with 5-ALA. This work demonstrates that panitumumab-IRDye800CW shows potential as a targeting agent for fluorescence intraoperative detection of GBM. Improved margin definition and surgical resection using panitumumab-IRDye800 has the potential to improve surgical outcomes and survival in patients with GBM compared with 5-ALA.